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pubmed23n0603_9924

Endoclipping for gastric perforation secondary to second session of EMRC in locally residual early gastric cancer: a case report.

A 72-year-old woman underwent gastric endoscopic mucosal resection with a cap-fitted endoscope for an adenocarcinoma in situ. She was scheduled for endoscopic follow-up at 1 and 3 months after the procedure. By the third month of follow up, biopsies of a slightly depressed scar area showed an high grade epithelial dysplasia. For this reason a second endoscopic resection (ER) was performed using the oblique soft cap. A perforation in the site of endoscopic resection was immediately observed. The complication was treated successfully by the application of seven clips.

Endoclipping for gastric perforation secondary to second session of EMRC in locally residual early gastric cancer: a case report. A 72-year-old woman underwent gastric endoscopic mucosal resection with a cap-fitted endoscope for an adenocarcinoma in situ. She was scheduled for endoscopic follow-up at 1 and 3 months after the procedure. By the third month of follow up, biopsies of a slightly depressed scar area showed an high grade epithelial dysplasia. For this reason a second endoscopic resection (ER) was performed using the oblique soft cap. A perforation in the site of endoscopic resection was immediately observed. The complication was treated successfully by the application of seven clips.

pubmed23n0972_21192

Influence of signal filtering and sample rate on isometric torque - time parameters using a traditional isokinetic dynamometer.

Isometric force- or torque-time parameters are commonly reported in the research literature. The processing methods of the electronic dynamometer-derived signal may influence the outcome measures. This study determined the influence of filtering and sample rate (SR) on isometric torque-time parameters and provides specific signal processing recommendations for future studies. Twenty-three subjects performed 49 isometric maximum voluntary contractions (MVCs) of the knee extensors on an isokinetic dynamometer. Outcome measures included peak torque (PT), and rate of torque development at peak (RTDPEAK), 50 (RTD50) and 200 (RTD200) ms for seven filter conditions including low-pass filter cutoffs at 5, 10, 20, 50, 100 and 150 Hz and a notch filter at 100 and 200 Hz. Comparisons were also made across four SR conditions at 100, 500, 1000 and 2000 Hz. The RTDPEAK variable was markedly changed (-5.4 to -37.9%) for all filter frequencies compared to the 150 Hz condition and the RTD50 variable was altered for all frequencies between 50 and 5 Hz. No differences were found for RTD200. For SR, compared to the 2000 Hz condition, differences were revealed for the 100 Hz condition for the RTDPEAK and RTD50 variables. The filtering or SR did not alter PT across any of the conditions. The filter and SR applied to the signal was capable of distorting the MVC signal and skewing the torque-time parameters, specifically for the early and maximum RTD variables of the MVC curve (RTD50 and RTDPEAK). For traditional isokinetic dynamometers, a low-pass filter cutoff of 150 Hz and a SR of at least 1000 Hz is recommended when assessing early isometric force- or torque-time MVC parameters.

Influence of signal filtering and sample rate on isometric torque - time parameters using a traditional isokinetic dynamometer. Isometric force- or torque-time parameters are commonly reported in the research literature. The processing methods of the electronic dynamometer-derived signal may influence the outcome measures. This study determined the influence of filtering and sample rate (SR) on isometric torque-time parameters and provides specific signal processing recommendations for future studies. Twenty-three subjects performed 49 isometric maximum voluntary contractions (MVCs) of the knee extensors on an isokinetic dynamometer. Outcome measures included peak torque (PT), and rate of torque development at peak (RTDPEAK), 50 (RTD50) and 200 (RTD200) ms for seven filter conditions including low-pass filter cutoffs at 5, 10, 20, 50, 100 and 150 Hz and a notch filter at 100 and 200 Hz. Comparisons were also made across four SR conditions at 100, 500, 1000 and 2000 Hz. The RTDPEAK variable was markedly changed (-5.4 to -37.9%) for all filter frequencies compared to the 150 Hz condition and the RTD50 variable was altered for all frequencies between 50 and 5 Hz. No differences were found for RTD200. For SR, compared to the 2000 Hz condition, differences were revealed for the 100 Hz condition for the RTDPEAK and RTD50 variables. The filtering or SR did not alter PT across any of the conditions. The filter and SR applied to the signal was capable of distorting the MVC signal and skewing the torque-time parameters, specifically for the early and maximum RTD variables of the MVC curve (RTD50 and RTDPEAK). For traditional isokinetic dynamometers, a low-pass filter cutoff of 150 Hz and a SR of at least 1000 Hz is recommended when assessing early isometric force- or torque-time MVC parameters.

pubmed23n0692_23639

Class III β-tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer.

The Class III β-tubulin isotype (βIII-tubulin) is a predictive biomarker in ovarian cancer and other solid tumor malignancies. We discovered that βIII-tubulin function is linked to two GTPases: guanylate-binding protein 1 (GBP1), which activates its function, and GNAI1, which inhibits it. This finding was demonstrated in a panel of ovarian cancer cells resistant to several chemotherapeutic agents. Using a protein microarray, we identified PIM1 as the downstream partner of GBP1, recruited into the cytoskeleton under hypoxic conditions. The clinical value of these observations was tested by performing an archive study of 98 ovarian cancer patients, which demonstrated that the βIII-tubulin -/PIM1- cohort responded to treatment, exhibiting long overall survival (OS), while βIII-tubulin +/PIM+ patients experienced poor outcomes and OS times similar to patients receiving palliation alone. βIII-tubulin expression is commonly believed responsible for paclitaxel resistance due to its enhancement of the dynamic instability of microtubules, which counteracts the activity of taxanes. In contrast, our research reveals that βIII-tubulin behaves as a gateway for prosurvival signals, such as PIM1, to move into the cytoskeleton. When cells are exposed to microenvironmental stressors, they activate this pathway by telling the cytoskeleton to incorporate PIM1 through GBP1 and βIII-tubulin, which ultimately leads to drug resistance. This discovery reveals that βIII-tubulin does not act alone but requires partners to play its role. The discovery of such protein:protein interactions underlying this prosurvival cascade makes feasible the development of therapeutic approaches using novel compounds that are capable of inhibiting the transmission of prosurvival signals into the cytoskeleton.

Class III β-tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer. The Class III β-tubulin isotype (βIII-tubulin) is a predictive biomarker in ovarian cancer and other solid tumor malignancies. We discovered that βIII-tubulin function is linked to two GTPases: guanylate-binding protein 1 (GBP1), which activates its function, and GNAI1, which inhibits it. This finding was demonstrated in a panel of ovarian cancer cells resistant to several chemotherapeutic agents. Using a protein microarray, we identified PIM1 as the downstream partner of GBP1, recruited into the cytoskeleton under hypoxic conditions. The clinical value of these observations was tested by performing an archive study of 98 ovarian cancer patients, which demonstrated that the βIII-tubulin -/PIM1- cohort responded to treatment, exhibiting long overall survival (OS), while βIII-tubulin +/PIM+ patients experienced poor outcomes and OS times similar to patients receiving palliation alone. βIII-tubulin expression is commonly believed responsible for paclitaxel resistance due to its enhancement of the dynamic instability of microtubules, which counteracts the activity of taxanes. In contrast, our research reveals that βIII-tubulin behaves as a gateway for prosurvival signals, such as PIM1, to move into the cytoskeleton. When cells are exposed to microenvironmental stressors, they activate this pathway by telling the cytoskeleton to incorporate PIM1 through GBP1 and βIII-tubulin, which ultimately leads to drug resistance. This discovery reveals that βIII-tubulin does not act alone but requires partners to play its role. The discovery of such protein:protein interactions underlying this prosurvival cascade makes feasible the development of therapeutic approaches using novel compounds that are capable of inhibiting the transmission of prosurvival signals into the cytoskeleton.

pubmed23n0095_11545

Agitation observed during treatment with newer hypnotic drugs.

Side effects involving agitation, e.g., sleepwalking, anger, and panic, were observed in 10 insomniac patients treated with temazepam or triazolam but not other benzodiazepines. Each patient described these side effects as uncharacteristic. Milder agitation was observed in 2 cases. In 4 cases, these effects were doubted by the prescribing physician. This type of side effect has been only slowly recognized for other benzodiazepines and has not been much reported for these newer agents. Agitation observed during treatment with these agents may be related to their short elimination half-lives.

Agitation observed during treatment with newer hypnotic drugs. Side effects involving agitation, e.g., sleepwalking, anger, and panic, were observed in 10 insomniac patients treated with temazepam or triazolam but not other benzodiazepines. Each patient described these side effects as uncharacteristic. Milder agitation was observed in 2 cases. In 4 cases, these effects were doubted by the prescribing physician. This type of side effect has been only slowly recognized for other benzodiazepines and has not been much reported for these newer agents. Agitation observed during treatment with these agents may be related to their short elimination half-lives.

pubmed23n0053_20772

Characterization of a human endometrial carcinoma cell line producing intraperitoneal tumor growth in immunodeficient mice.

Establishment of laboratory models of gynecologic neoplasms provides an important means of studying the biologic characteristics of these tumors. We report a previously uncharacterized human endometrial adenocarcinoma cell line that produces both intraperitoneal and subcutaneous growth in nude mice. The line was derived from a poorly differentiated endometrial cancer and has been carried in continuous tissue culture for greater than 100 passages. Doubling time in culture is approximately 48 hr. Antigenic phenotyping against a panel of murine monoclonal antibodies by rosetting cell surface assay on live cells or peroxidase assay on fixed cells has shown reactivity with a number of determinants, including MH99, MT334, MQ49, and the blood group antigens F3, 118, and 41-83. Cytogenetically, the line displays an aneuploid human karyotype with several chromosomal rearrangements and deletions. When injected intraperitoneally into nude mice, animals develop intraperitoneal nodules and ascites and succumb with wasting in 30-40 days. The intraperitoneal tumor has been passaged multiple times in nude mice by direct transfer of ascites. Subcutaneous injection of tumor cells produces nodules that grow at a reproducible rate. By light and electron microscopy, the nude mouse tumor is a poorly differentiated adenocarcinoma, similar to the original patient's tumor. It expresses both estrogen and progesterone receptors. CA 125 is not elevated in the serum of animals with tumor implants. The line appears to be cisplatin sensitive as determined by rates of growth of subcutaneous nodules. This cell line may be useful in studying the in vitro and in vivo properties of human endometrial carcinoma.

Characterization of a human endometrial carcinoma cell line producing intraperitoneal tumor growth in immunodeficient mice. Establishment of laboratory models of gynecologic neoplasms provides an important means of studying the biologic characteristics of these tumors. We report a previously uncharacterized human endometrial adenocarcinoma cell line that produces both intraperitoneal and subcutaneous growth in nude mice. The line was derived from a poorly differentiated endometrial cancer and has been carried in continuous tissue culture for greater than 100 passages. Doubling time in culture is approximately 48 hr. Antigenic phenotyping against a panel of murine monoclonal antibodies by rosetting cell surface assay on live cells or peroxidase assay on fixed cells has shown reactivity with a number of determinants, including MH99, MT334, MQ49, and the blood group antigens F3, 118, and 41-83. Cytogenetically, the line displays an aneuploid human karyotype with several chromosomal rearrangements and deletions. When injected intraperitoneally into nude mice, animals develop intraperitoneal nodules and ascites and succumb with wasting in 30-40 days. The intraperitoneal tumor has been passaged multiple times in nude mice by direct transfer of ascites. Subcutaneous injection of tumor cells produces nodules that grow at a reproducible rate. By light and electron microscopy, the nude mouse tumor is a poorly differentiated adenocarcinoma, similar to the original patient's tumor. It expresses both estrogen and progesterone receptors. CA 125 is not elevated in the serum of animals with tumor implants. The line appears to be cisplatin sensitive as determined by rates of growth of subcutaneous nodules. This cell line may be useful in studying the in vitro and in vivo properties of human endometrial carcinoma.

pubmed23n0251_20008

Virtual reality for physically disabled people.

This paper demonstrates how physically disabled people can benefit from the innovative virtual reality techniques. Several specific examples show the applicability of virtual reality to the therapy and rehabilitation of people with various disabilities. In addition, the paper describes how physicians can use virtual reality as an advanced visualization tool for the diagnosis of physical disabilities. Finally, possible display techniques and input devices for diagnosis and rehabilitation purposes are discussed briefly.

Virtual reality for physically disabled people. This paper demonstrates how physically disabled people can benefit from the innovative virtual reality techniques. Several specific examples show the applicability of virtual reality to the therapy and rehabilitation of people with various disabilities. In addition, the paper describes how physicians can use virtual reality as an advanced visualization tool for the diagnosis of physical disabilities. Finally, possible display techniques and input devices for diagnosis and rehabilitation purposes are discussed briefly.

pubmed23n0963_21426

Mortality after pancreaticoduodenectomy: assessing early and late causes of patient death.

Safety of pancreaticoduodenectomy has improved significantly in the past 3 decades. Current inpatient and 30-d mortality rates are low. However, incidence and causes of 90-d and 1-y mortality are poorly defined and largely unexplored. All patients who had pancreaticoduodenectomy between 2007 and 2016 were included in this single institution, retrospective cohort study. Distributions of pancreaticoduodenectomy-specific morbidity and cause-specific mortality were compared between early (within 90 d) and late (91-365 d) postoperative recovery periods. A total of 551 pancreaticoduodenectomies were performed during the study period. Of these, 6 (1.1%), 20 (3.6%), and 91 (16.5%) patients died within 30, 90, and 365 d after pancreaticoduodenectomy, respectively. Causes of early and late mortality varied significantly (all P ≤ 0.032). The most common cause of death within 90 d was due to multisystem organ failure from sepsis or aspiration in 9 (45%) patients, followed by post-pancreatectomy hemorrhage in 5 (25%) patients, and cardiopulmonary arrest from myocardial infarction or pulmonary embolus in 3 (15%) patients. In contrast, recurrent cancer was the most common cause of death in 46 (65%) patients during the late postoperative period between 91 and 365 d. Mortality from failure to thrive and debility was similar between early and late postoperative periods (15% versus 19.7%, P = 0.76). Most quality improvement initiatives in patients selected for pancreaticoduodenectomy have focused on reduction of technical complications and improvement of early postoperative mortality. Further reduction in postoperative mortality after pancreaticoduodenectomy can be achieved by improving patient selection, mitigating postoperative malnutrition, and optimizing preoperative cancer staging and management strategies.

Mortality after pancreaticoduodenectomy: assessing early and late causes of patient death. Safety of pancreaticoduodenectomy has improved significantly in the past 3 decades. Current inpatient and 30-d mortality rates are low. However, incidence and causes of 90-d and 1-y mortality are poorly defined and largely unexplored. All patients who had pancreaticoduodenectomy between 2007 and 2016 were included in this single institution, retrospective cohort study. Distributions of pancreaticoduodenectomy-specific morbidity and cause-specific mortality were compared between early (within 90 d) and late (91-365 d) postoperative recovery periods. A total of 551 pancreaticoduodenectomies were performed during the study period. Of these, 6 (1.1%), 20 (3.6%), and 91 (16.5%) patients died within 30, 90, and 365 d after pancreaticoduodenectomy, respectively. Causes of early and late mortality varied significantly (all P ≤ 0.032). The most common cause of death within 90 d was due to multisystem organ failure from sepsis or aspiration in 9 (45%) patients, followed by post-pancreatectomy hemorrhage in 5 (25%) patients, and cardiopulmonary arrest from myocardial infarction or pulmonary embolus in 3 (15%) patients. In contrast, recurrent cancer was the most common cause of death in 46 (65%) patients during the late postoperative period between 91 and 365 d. Mortality from failure to thrive and debility was similar between early and late postoperative periods (15% versus 19.7%, P = 0.76). Most quality improvement initiatives in patients selected for pancreaticoduodenectomy have focused on reduction of technical complications and improvement of early postoperative mortality. Further reduction in postoperative mortality after pancreaticoduodenectomy can be achieved by improving patient selection, mitigating postoperative malnutrition, and optimizing preoperative cancer staging and management strategies.

pubmed23n1118_7736

Fibrous Polymer-Based Composites Obtained by Electrospinning for Bone Tissue Engineering.

Currently, the significantly developing fields of tissue engineering related to the fabrication of polymer-based materials that possess microenvironments suitable to provide cell attachment and promote cell differentiation and proliferation involve various materials and approaches. Biomimicking approach in tissue engineering is aimed at the development of a highly biocompatible and bioactive material that would most accurately imitate the structural features of the native extracellular matrix consisting of specially arranged fibrous constructions. For this reason, the present research is devoted to the discussion of promising fibrous materials for bone tissue regeneration obtained by electrospinning techniques. In this brief review, we focus on the recently presented natural and synthetic polymers, as well as their combinations with each other and with bioactive inorganic incorporations in order to form composite electrospun scaffolds. The application of several electrospinning techniques in relation to a number of polymers is touched upon. Additionally, the efficiency of nanofibrous composite materials intended for use in bone tissue engineering is discussed based on biological activity and physiochemical characteristics.

Fibrous Polymer-Based Composites Obtained by Electrospinning for Bone Tissue Engineering. Currently, the significantly developing fields of tissue engineering related to the fabrication of polymer-based materials that possess microenvironments suitable to provide cell attachment and promote cell differentiation and proliferation involve various materials and approaches. Biomimicking approach in tissue engineering is aimed at the development of a highly biocompatible and bioactive material that would most accurately imitate the structural features of the native extracellular matrix consisting of specially arranged fibrous constructions. For this reason, the present research is devoted to the discussion of promising fibrous materials for bone tissue regeneration obtained by electrospinning techniques. In this brief review, we focus on the recently presented natural and synthetic polymers, as well as their combinations with each other and with bioactive inorganic incorporations in order to form composite electrospun scaffolds. The application of several electrospinning techniques in relation to a number of polymers is touched upon. Additionally, the efficiency of nanofibrous composite materials intended for use in bone tissue engineering is discussed based on biological activity and physiochemical characteristics.

pubmed23n0392_8458

[The arginine paradox].

L-Arginine has attracted major interest because it has been identified as the natural substrate of nitric oxide synthase and is now recognized as a major player in the regulation of biological function. The arginine paradox refers to the phenomenon that exogenous L-arginine causes NO-mediated biological effects despite the fact that nitric oxide synthases (NOS) are theoretically saturated with the substrate L-arginine. There have been several explanations for this phenomenon, although none of them can explain the arginine paradox fully: (1) L-arginine-induced insulin, which has vasodilatory actions. (2) Neither extracellular nor intracellular concentration determines the NOS activity but rather the L-arginine amount transported across the plasma membrane may do so. (3) Endogenous NOS inhibitors reduce the enzyme sensitivity to L-arginine. These inhibitors include, NG, NG-dimethyl-L-arginine, L-citrulline, argininosuccinic acid and agmatine. (4) Intracellular L-citrulline, an NOS product, is a potent inhibitor of NOS so that the cells may need extra L-arginine to compete with L-citrulline inhibition.

[The arginine paradox]. L-Arginine has attracted major interest because it has been identified as the natural substrate of nitric oxide synthase and is now recognized as a major player in the regulation of biological function. The arginine paradox refers to the phenomenon that exogenous L-arginine causes NO-mediated biological effects despite the fact that nitric oxide synthases (NOS) are theoretically saturated with the substrate L-arginine. There have been several explanations for this phenomenon, although none of them can explain the arginine paradox fully: (1) L-arginine-induced insulin, which has vasodilatory actions. (2) Neither extracellular nor intracellular concentration determines the NOS activity but rather the L-arginine amount transported across the plasma membrane may do so. (3) Endogenous NOS inhibitors reduce the enzyme sensitivity to L-arginine. These inhibitors include, NG, NG-dimethyl-L-arginine, L-citrulline, argininosuccinic acid and agmatine. (4) Intracellular L-citrulline, an NOS product, is a potent inhibitor of NOS so that the cells may need extra L-arginine to compete with L-citrulline inhibition.

pubmed23n1021_14936

Clinical outcomes of stereotactic body radiation therapy for small hepatocellular carcinoma.

The purpose of this study was to investigate the long-term oncologic outcomes after stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC). A total of 290 patients with HCC were registered between March 2007 and July 2013. A dose of 10-15 Gy per fraction was given over three to four consecutive days, resulting in a total dose of 30-60 Gy. Overall and recurrence-free survivals were estimated from the date of the start of SBRT to the date of death, the last follow-up examination, or to the date of tumor recurrence. The median follow-up period of all patients was 38.2 months, and the median tumor size was 1.7 cm. Overall survival (OS) rate at 5 years was 44.9%. Multivariate analyses revealed that age, Child-Pugh class, tumor size, and albumin levels were significant factors for OS. The 5-year local control rate was 91.3%. In multivariate analysis, tumor size and albumin were significantly associated with local tumor control. However, there was a negative correlation between total dose and tumor size in Pearson's correlation analysis (r = -0.111, P = 0.046). Stereotactic body radiation therapy was an excellent ablative treatment option for patients with small HCC. Tumor size was a significant factor for local tumor control after SBRT, although the total dose was negatively correlated with tumor size. Considering the low OS rates and the high local tumor control rates, the combined SBRT and systemic therapies may be beneficial for improving survival outcomes.

Clinical outcomes of stereotactic body radiation therapy for small hepatocellular carcinoma. The purpose of this study was to investigate the long-term oncologic outcomes after stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC). A total of 290 patients with HCC were registered between March 2007 and July 2013. A dose of 10-15 Gy per fraction was given over three to four consecutive days, resulting in a total dose of 30-60 Gy. Overall and recurrence-free survivals were estimated from the date of the start of SBRT to the date of death, the last follow-up examination, or to the date of tumor recurrence. The median follow-up period of all patients was 38.2 months, and the median tumor size was 1.7 cm. Overall survival (OS) rate at 5 years was 44.9%. Multivariate analyses revealed that age, Child-Pugh class, tumor size, and albumin levels were significant factors for OS. The 5-year local control rate was 91.3%. In multivariate analysis, tumor size and albumin were significantly associated with local tumor control. However, there was a negative correlation between total dose and tumor size in Pearson's correlation analysis (r = -0.111, P = 0.046). Stereotactic body radiation therapy was an excellent ablative treatment option for patients with small HCC. Tumor size was a significant factor for local tumor control after SBRT, although the total dose was negatively correlated with tumor size. Considering the low OS rates and the high local tumor control rates, the combined SBRT and systemic therapies may be beneficial for improving survival outcomes.

pubmed23n0945_3031

Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data. In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells. Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD.

Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson's Disease. Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data. In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells. Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD.

pubmed23n0318_18215

Xa21D encodes a receptor-like molecule with a leucine-rich repeat domain that determines race-specific recognition and is subject to adaptive evolution.

The rice Xa21 gene confers resistance to Xanthomonas oryzae pv oryzae in a race-specific manner. Analysis of the inheritance patterns and resistance spectra of transgenic plants carrying six Xa21 gene family members indicated that one member, designated Xa21D, displayed a resistance spectrum identical to that observed for Xa21 but conferred only partial resistance. Xa21D encodes a receptor-like protein carrying leucine-rich repeat (LRR) motifs in the presumed extracellular domain. The Xa21D transcript terminates shortly after the stop codon introduced by the retrotransposon Retrofit. Comparison of nucleotide substitutions in the LRR coding regions of Xa21 and Xa21D provided evidence of adaptive selection. Both functional and evolutionary evidence indicates that the Xa21D LRR domain controls race-specific pathogen recognition.

Xa21D encodes a receptor-like molecule with a leucine-rich repeat domain that determines race-specific recognition and is subject to adaptive evolution. The rice Xa21 gene confers resistance to Xanthomonas oryzae pv oryzae in a race-specific manner. Analysis of the inheritance patterns and resistance spectra of transgenic plants carrying six Xa21 gene family members indicated that one member, designated Xa21D, displayed a resistance spectrum identical to that observed for Xa21 but conferred only partial resistance. Xa21D encodes a receptor-like protein carrying leucine-rich repeat (LRR) motifs in the presumed extracellular domain. The Xa21D transcript terminates shortly after the stop codon introduced by the retrotransposon Retrofit. Comparison of nucleotide substitutions in the LRR coding regions of Xa21 and Xa21D provided evidence of adaptive selection. Both functional and evolutionary evidence indicates that the Xa21D LRR domain controls race-specific pathogen recognition.

pubmed23n0593_22197

Consistency of complex fractionated atrial electrograms during atrial fibrillation.

Temporal variation in complex fractionated atrial electrograms (CFAEs) exists during atrial fibrillation (AF). This study sought to quantify the variation in CFAEs using a fractionation interval (FI) algorithm and to define the shortest optimal recording duration required to consistently characterize the magnitude of the fractionation. Twenty-seven patients undergoing AF mapping in the left atrium were studied. The FI and frequency analysis were performed at each mapped site for recording durations of 1 to 8 seconds. The magnitude of the fractionation was quantified by the FI algorithm, which calculated the mean interval between multiple, discrete deflections during AF. The results from each duration were statistically compared with the maximal-duration recording, as a standard. The FI values were compared with the dominant frequency values obtained from the associated frequency spectra. The FIs obtained from recording durations between 5 and 8 seconds had a smaller variation in the FI (P < .05) and, for those sites with a FI < 50 ms, the fractionation was typically continuous. The fast-Fourier Transform spectra obtained from the CFAE sites with recording durations of >5 seconds harbored higher dominant frequency values than those with shorter recording durations (8.1 +/- 2.5 Hz vs. 6.8 +/- 0.98 Hz, P < .05). The CFAE sites with continuous fractionation were located within the pulmonary veins and their ostia in 77% of patients with paroxysmal AF, and in only 29% of patients with nonparoxysmal AF (P < .05). The assessment of fractionated electrograms requires a recording duration of > or =5 seconds at each site to obtain a consistent fractionation. Sites with the shortest FIs consistently identified sites with the fastest electrogram activity throughout the entire left atrium and pulmonary veins.

Consistency of complex fractionated atrial electrograms during atrial fibrillation. Temporal variation in complex fractionated atrial electrograms (CFAEs) exists during atrial fibrillation (AF). This study sought to quantify the variation in CFAEs using a fractionation interval (FI) algorithm and to define the shortest optimal recording duration required to consistently characterize the magnitude of the fractionation. Twenty-seven patients undergoing AF mapping in the left atrium were studied. The FI and frequency analysis were performed at each mapped site for recording durations of 1 to 8 seconds. The magnitude of the fractionation was quantified by the FI algorithm, which calculated the mean interval between multiple, discrete deflections during AF. The results from each duration were statistically compared with the maximal-duration recording, as a standard. The FI values were compared with the dominant frequency values obtained from the associated frequency spectra. The FIs obtained from recording durations between 5 and 8 seconds had a smaller variation in the FI (P < .05) and, for those sites with a FI < 50 ms, the fractionation was typically continuous. The fast-Fourier Transform spectra obtained from the CFAE sites with recording durations of >5 seconds harbored higher dominant frequency values than those with shorter recording durations (8.1 +/- 2.5 Hz vs. 6.8 +/- 0.98 Hz, P < .05). The CFAE sites with continuous fractionation were located within the pulmonary veins and their ostia in 77% of patients with paroxysmal AF, and in only 29% of patients with nonparoxysmal AF (P < .05). The assessment of fractionated electrograms requires a recording duration of > or =5 seconds at each site to obtain a consistent fractionation. Sites with the shortest FIs consistently identified sites with the fastest electrogram activity throughout the entire left atrium and pulmonary veins.

pubmed23n0836_12851

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: long-term results at St George Hospital, Australia.

Peritoneal carcinomatosis (PC) results from the secondary spread of many intraabdominal tumour types, such as colorectal malignancy (colorectal cancer, CRC), disseminated peritoneal adenomucinosis (DPAM), appendiceal cancer, ovarian carcinoma, sarcoma or from the occurrence of primary peritoneal disease such as peritoneal mesothelioma. The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has seen improvements in survival in selected cases of these cancers. Between 1996 and 2014, a prospective database of 675 patients was created for the peritonectomy unit at our hospital. In total, 827 peritonectomy procedures (including redo CRS) were performed for the major subgroups of PC: DPAM 220; appendiceal cancer (peritoneal mucinous adenocarcinoma (PMCA)) 191; CRC 234; diffuse malignant peritoneal mesothelioma (DMPM) 73 and others 109. There were 152 redo-peritonectomy procedures within the total mentioned earlier (CRC 26; DPAM 58; DMPM 18; appendix 40; other 10). The 5-year survivals for DPAM and PMCA were 80% and 42% respectively. The 5-year survivals for appendiceal cancer with peritoneal cancer index (PCI) <10, 10-20 and >20 were 60, 57 and 37% respectively (P = 0.09). The 2- and 5-year survivals for CRC were 56 and 24% respectively. The 5-year survivals for PCI 0-5, 6-10, 11-15 and >15 were 59, 15, 7 and 0% respectively (P = 0.000). The 5-year survival for DMPM with PCI < 10, 10-20 and >20 were 100, 55 and 39% respectively (P = 0.01). CRS in combination with HIPEC provides a chance of long-term survival in selected cases of PC when compared with systemic therapy alone.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: long-term results at St George Hospital, Australia. Peritoneal carcinomatosis (PC) results from the secondary spread of many intraabdominal tumour types, such as colorectal malignancy (colorectal cancer, CRC), disseminated peritoneal adenomucinosis (DPAM), appendiceal cancer, ovarian carcinoma, sarcoma or from the occurrence of primary peritoneal disease such as peritoneal mesothelioma. The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has seen improvements in survival in selected cases of these cancers. Between 1996 and 2014, a prospective database of 675 patients was created for the peritonectomy unit at our hospital. In total, 827 peritonectomy procedures (including redo CRS) were performed for the major subgroups of PC: DPAM 220; appendiceal cancer (peritoneal mucinous adenocarcinoma (PMCA)) 191; CRC 234; diffuse malignant peritoneal mesothelioma (DMPM) 73 and others 109. There were 152 redo-peritonectomy procedures within the total mentioned earlier (CRC 26; DPAM 58; DMPM 18; appendix 40; other 10). The 5-year survivals for DPAM and PMCA were 80% and 42% respectively. The 5-year survivals for appendiceal cancer with peritoneal cancer index (PCI) <10, 10-20 and >20 were 60, 57 and 37% respectively (P = 0.09). The 2- and 5-year survivals for CRC were 56 and 24% respectively. The 5-year survivals for PCI 0-5, 6-10, 11-15 and >15 were 59, 15, 7 and 0% respectively (P = 0.000). The 5-year survival for DMPM with PCI < 10, 10-20 and >20 were 100, 55 and 39% respectively (P = 0.01). CRS in combination with HIPEC provides a chance of long-term survival in selected cases of PC when compared with systemic therapy alone.

pubmed23n1151_8670

Correction.

[This corrects the article on p. 204 in vol. 7.].

Correction. [This corrects the article on p. 204 in vol. 7.].

pubmed23n0648_16030

Symmetrization of the AMBER and CHARMM force fields.

The AMBER and CHARMM force fields are analyzed from the viewpoint of the permutational symmetry of the potential for feasible exchanges of identical atoms and chemical groups in amino and nucleic acids. In each case, we propose schemes for symmetrizing the potentials, which greatly facilitate the bookkeeping associated with constructing kinetic transition networks via geometry optimization.

Symmetrization of the AMBER and CHARMM force fields. The AMBER and CHARMM force fields are analyzed from the viewpoint of the permutational symmetry of the potential for feasible exchanges of identical atoms and chemical groups in amino and nucleic acids. In each case, we propose schemes for symmetrizing the potentials, which greatly facilitate the bookkeeping associated with constructing kinetic transition networks via geometry optimization.

pubmed23n0942_13991

Comparison of body image perception, nutrition knowledge, dietary attitudes, and dietary habits between Korean and Mongolian college students.

College students are in transition from adolescence to adulthood, and it has been reported that they show poor dietary habits. This study was conducted to compare body image perception, nutrition knowledge, dietary attitudes, dietary habits, and health-related lifestyles between Korean college students (KCS) and Mongolian college students (MCS). Subjects were 314 KCS and 280 MCS. The data includes results of self-administered questionnaires; statistical analysis was performed using the SPSS 23.0 program. With regards to body image perception, KCS perceived themselves to be fatter on current body image than ideal body image compared to MCS; 64.0% of KCS and 34.6% of MCS desired to be thinner. Total score of nutrition knowledge in KCS (17.0) was significantly higher compared to MCS (8.4) (<iP</i &lt; 0.001), but total score of dietary attitudes in KCS (27.0) was significantly lower compared to MCS (31.2) (<iP</i &lt; 0.001). Nutrition knowledge had a significantly positive correlation with dietary attitudes in MCS (<iP</i &lt; 0.01). Meal consumption among male and female subjects was 2 and 3 times, respectively, in order in KCS, and 3 and 2 times, respectively, in order in MCS (<iP</i &lt; 0.001). Rate of skipping breakfast in both genders was significantly higher in KCS than in MCS (male: <iP</i &lt; 0.05, female: <iP</i &lt; 0.001). In health-related lifestyles, KCS had a significantly higher rate in frequency of alcohol drinking (<iP</i &lt; 0.001), exercise (<iP</i &lt; 0.01), and mobile phone usage (<iP</i &lt; 0.001), compared to MCS. This study suggests that development of nutrition education program which is effective and proper is required to improve healthy dietary habits among college students of both countries. Essential contents should include acquirement of nutrition knowledge and a motivation for its application to actual life for KCS, and improvement of healthy dietary habits for MCS.

Comparison of body image perception, nutrition knowledge, dietary attitudes, and dietary habits between Korean and Mongolian college students. College students are in transition from adolescence to adulthood, and it has been reported that they show poor dietary habits. This study was conducted to compare body image perception, nutrition knowledge, dietary attitudes, dietary habits, and health-related lifestyles between Korean college students (KCS) and Mongolian college students (MCS). Subjects were 314 KCS and 280 MCS. The data includes results of self-administered questionnaires; statistical analysis was performed using the SPSS 23.0 program. With regards to body image perception, KCS perceived themselves to be fatter on current body image than ideal body image compared to MCS; 64.0% of KCS and 34.6% of MCS desired to be thinner. Total score of nutrition knowledge in KCS (17.0) was significantly higher compared to MCS (8.4) (<iP</i &lt; 0.001), but total score of dietary attitudes in KCS (27.0) was significantly lower compared to MCS (31.2) (<iP</i &lt; 0.001). Nutrition knowledge had a significantly positive correlation with dietary attitudes in MCS (<iP</i &lt; 0.01). Meal consumption among male and female subjects was 2 and 3 times, respectively, in order in KCS, and 3 and 2 times, respectively, in order in MCS (<iP</i &lt; 0.001). Rate of skipping breakfast in both genders was significantly higher in KCS than in MCS (male: <iP</i &lt; 0.05, female: <iP</i &lt; 0.001). In health-related lifestyles, KCS had a significantly higher rate in frequency of alcohol drinking (<iP</i &lt; 0.001), exercise (<iP</i &lt; 0.01), and mobile phone usage (<iP</i &lt; 0.001), compared to MCS. This study suggests that development of nutrition education program which is effective and proper is required to improve healthy dietary habits among college students of both countries. Essential contents should include acquirement of nutrition knowledge and a motivation for its application to actual life for KCS, and improvement of healthy dietary habits for MCS.

pubmed23n0363_20096

Non-familial haemophagocytic lymphohistiocytosis in children.

Haemophagocytic Lymphohistiocytosis (HLH) is a rare clinical illness with a high mortality. There are reported effective treatment and a favourable outcome if diagnosed early. Five cases of childhood non-familial HLH seen over a 3 year period in our hospital are presented. The diagnosis was not suspected in the referring hospitals even after a bone marrow biopsy examination in two cases. Delay in referral was between 2 weeks to 2 months. A viral trigger was detected in only two cases. There were two deaths. Cause of death in both cases were cytomegalovirus pneumonitis and disseminated intravascular coagulopathy. Respond to treatment was better if started earlier. One case spontaneously resolved. Earlier diagnosis will lead to prompt treatment and a better outcome.

Non-familial haemophagocytic lymphohistiocytosis in children. Haemophagocytic Lymphohistiocytosis (HLH) is a rare clinical illness with a high mortality. There are reported effective treatment and a favourable outcome if diagnosed early. Five cases of childhood non-familial HLH seen over a 3 year period in our hospital are presented. The diagnosis was not suspected in the referring hospitals even after a bone marrow biopsy examination in two cases. Delay in referral was between 2 weeks to 2 months. A viral trigger was detected in only two cases. There were two deaths. Cause of death in both cases were cytomegalovirus pneumonitis and disseminated intravascular coagulopathy. Respond to treatment was better if started earlier. One case spontaneously resolved. Earlier diagnosis will lead to prompt treatment and a better outcome.

pubmed23n0203_9427

Activity ratio between antiprostacyclin and antiaggregating effects of acetylsalicylic acid, indometacin and ditazole.

The effects of acetylsalicylic acid (ASA) indometacin and ditazole on prostacyclin production from rabbit aortic rings were studied in comparison to their inhibiting activity on platelet aggregation. The result were expressed as the ratio between the drug dose inhibiting by 50% prostacycline production and the minimum oral antiaggregating dose. The following ratios were found: 2.4 for ASA, 7.3 for indometacin and 20.4 for ditazole.

Activity ratio between antiprostacyclin and antiaggregating effects of acetylsalicylic acid, indometacin and ditazole. The effects of acetylsalicylic acid (ASA) indometacin and ditazole on prostacyclin production from rabbit aortic rings were studied in comparison to their inhibiting activity on platelet aggregation. The result were expressed as the ratio between the drug dose inhibiting by 50% prostacycline production and the minimum oral antiaggregating dose. The following ratios were found: 2.4 for ASA, 7.3 for indometacin and 20.4 for ditazole.

pubmed23n0551_115

Quantity and distribution of eosinophils in the gastrointestinal tract of children.

There are a lack of data on the quantity and location of eosinophils in the gastrointestinal tract of healthy individuals. Accordingly, we examined gastrointestinal biopsies obtained during endoscopic evaluation of pediatric patients. Biopsies were previously interpreted as having no diagnostic abnormality. The presence of extracellular eosinophil constituents and the quantity of eosinophils in atopic versus nonatopic individuals was determined. In the esophagus, eosinophils were present in only 2.7% of high-power fields (hpf), with a mean value of 0.03+/-0.10 eosinophils/hpf (mean+/-standard deviation) and a maximum of 1 eosinophil/hpf. Examination of the antrum and fundus revealed similar numbers of eosinophils in the lamina propria (1.9+/-1.3 and 2.1+/-2.4 eosinophils/hpf, respectively), with no eosinophils observed in the surface epithelium. In the small intestine, there were 9.6+/-5.3 (maximum, 26 eosinophils/hpf) and 12.4+/-5.4 eosinophils/hpf (maximum, 28 eosinophils/hpf) in the intercryptal lamina propria of the duodenum and ileum, respectively. The number of eosinophils in the surface epithelium and crypt epithelium was minimal. In the large intestine, the highest concentration of eosinophils was observed in the cecum (20.3+/-8.2 eosinophils/hpf; maximum, 50 eosinophils/hpf), and there were lower concentrations in the transverse and sigmoid colon (16.3+/-5.6 and 8.3+/-5.9 eosinophils/hpf, respectively). The percentage of fields demonstrating extracellular eosinophil granules in all gastrointestinal segments was 70% to 93%, and extracellular granules were most numerous at the edge of the biopsy (P&lt;0.05). Atopic and nonatopic patients had comparable numbers of eosinophils. These data establish baseline gastrointestinal eosinophil values in pediatric patients without apparent pathological disease.

Quantity and distribution of eosinophils in the gastrointestinal tract of children. There are a lack of data on the quantity and location of eosinophils in the gastrointestinal tract of healthy individuals. Accordingly, we examined gastrointestinal biopsies obtained during endoscopic evaluation of pediatric patients. Biopsies were previously interpreted as having no diagnostic abnormality. The presence of extracellular eosinophil constituents and the quantity of eosinophils in atopic versus nonatopic individuals was determined. In the esophagus, eosinophils were present in only 2.7% of high-power fields (hpf), with a mean value of 0.03+/-0.10 eosinophils/hpf (mean+/-standard deviation) and a maximum of 1 eosinophil/hpf. Examination of the antrum and fundus revealed similar numbers of eosinophils in the lamina propria (1.9+/-1.3 and 2.1+/-2.4 eosinophils/hpf, respectively), with no eosinophils observed in the surface epithelium. In the small intestine, there were 9.6+/-5.3 (maximum, 26 eosinophils/hpf) and 12.4+/-5.4 eosinophils/hpf (maximum, 28 eosinophils/hpf) in the intercryptal lamina propria of the duodenum and ileum, respectively. The number of eosinophils in the surface epithelium and crypt epithelium was minimal. In the large intestine, the highest concentration of eosinophils was observed in the cecum (20.3+/-8.2 eosinophils/hpf; maximum, 50 eosinophils/hpf), and there were lower concentrations in the transverse and sigmoid colon (16.3+/-5.6 and 8.3+/-5.9 eosinophils/hpf, respectively). The percentage of fields demonstrating extracellular eosinophil granules in all gastrointestinal segments was 70% to 93%, and extracellular granules were most numerous at the edge of the biopsy (P&lt;0.05). Atopic and nonatopic patients had comparable numbers of eosinophils. These data establish baseline gastrointestinal eosinophil values in pediatric patients without apparent pathological disease.

pubmed23n1155_15361

The Effect of E-Learning Program for COVID-19 Patient Care on the Knowledge of Nursing Students: A Quasi-Experimental Study.

As COVID-19 is an emerging disease, nursing students have little experience in caring for COVID-19 patients while they will be part of the country's health system and have the closest relationship with the treatment team. Therefore, considering the importance and challenges of nursing students' education during the COVID-19 pandemic, the present study aimed to investigate the effect of e-learning programs for COVID-19 patient care on nursing students' knowledge in Tehran, Iran 2021. The present quasi-experimental study was performed on 100 nursing students selected by a random sampling method. The demographic and knowledge assessment questionnaires were used to collect data before the intervention. Then, the e-learning program was implemented, in which students participated in three sessions for two weeks, the educational content was provided for the students in the form of text, audio, video, and image files, and questions were asked to them. Data were collected immediately after completing the e-learning program and four weeks later. The mean age value was 22 ± 1.25, and 61% of participants were female. The total mean score of knowledge immediately after training (22.95 ± 0.30) and one month after training (22.79 ± 0.30) significantly increased compared to baseline time (17.21 ± 0.48). The main effect of time was significant for the total score of knowledge from baseline to immediately after training (B = 5.79) and one-month follow-up (B = 5.63). The findings of the study showed that the total mean score of the knowledge of students increased significantly in all dimensions after the e-learning program for COVID-19 patient care. Considering the effectiveness of the e-learning program for COVID-19 patient care in increasing the knowledge of nursing students, it is necessary to provide more training programs focusing on new scientific findings because increasing nurses' and nursing students' knowledge plays a significant role in achieving more skills and promoting community health.

The Effect of E-Learning Program for COVID-19 Patient Care on the Knowledge of Nursing Students: A Quasi-Experimental Study. As COVID-19 is an emerging disease, nursing students have little experience in caring for COVID-19 patients while they will be part of the country's health system and have the closest relationship with the treatment team. Therefore, considering the importance and challenges of nursing students' education during the COVID-19 pandemic, the present study aimed to investigate the effect of e-learning programs for COVID-19 patient care on nursing students' knowledge in Tehran, Iran 2021. The present quasi-experimental study was performed on 100 nursing students selected by a random sampling method. The demographic and knowledge assessment questionnaires were used to collect data before the intervention. Then, the e-learning program was implemented, in which students participated in three sessions for two weeks, the educational content was provided for the students in the form of text, audio, video, and image files, and questions were asked to them. Data were collected immediately after completing the e-learning program and four weeks later. The mean age value was 22 ± 1.25, and 61% of participants were female. The total mean score of knowledge immediately after training (22.95 ± 0.30) and one month after training (22.79 ± 0.30) significantly increased compared to baseline time (17.21 ± 0.48). The main effect of time was significant for the total score of knowledge from baseline to immediately after training (B = 5.79) and one-month follow-up (B = 5.63). The findings of the study showed that the total mean score of the knowledge of students increased significantly in all dimensions after the e-learning program for COVID-19 patient care. Considering the effectiveness of the e-learning program for COVID-19 patient care in increasing the knowledge of nursing students, it is necessary to provide more training programs focusing on new scientific findings because increasing nurses' and nursing students' knowledge plays a significant role in achieving more skills and promoting community health.

pubmed23n0264_4200

Comparison of the kinetic properties of MGDG synthase in mixed micelles and in envelope membranes from spinach chloroplast.

We have applied the 'membrane partition' kinetic modelling approach proposed by Heirwegh et al. [(1988) Biochem. J. 254, 101-108] to MGDG synthase in isolated envelope vesicles. Comparison of the kinetic parameters obtained for MGDG synthase assayed in purified envelope membranes and in mixed-micelles demonstrates that the latter are relevant to the situation in envelope membranes and that MGDG synthase has a very high affinity for dilinoleoylglycerol. Our results provide additional evidence for the hypothesis that the high affinity of the envelope MGDG synthase for dilinoleoylglycerol could be responsible for the presence of C18 fatty acids at both the sn-1 and sn-2 position of the glycerol backbone in MGDG.

Comparison of the kinetic properties of MGDG synthase in mixed micelles and in envelope membranes from spinach chloroplast. We have applied the 'membrane partition' kinetic modelling approach proposed by Heirwegh et al. [(1988) Biochem. J. 254, 101-108] to MGDG synthase in isolated envelope vesicles. Comparison of the kinetic parameters obtained for MGDG synthase assayed in purified envelope membranes and in mixed-micelles demonstrates that the latter are relevant to the situation in envelope membranes and that MGDG synthase has a very high affinity for dilinoleoylglycerol. Our results provide additional evidence for the hypothesis that the high affinity of the envelope MGDG synthase for dilinoleoylglycerol could be responsible for the presence of C18 fatty acids at both the sn-1 and sn-2 position of the glycerol backbone in MGDG.

pubmed23n1150_9503

A comparative study of adjuvants effects on neonatal plasma cell survival niche in bone marrow and persistence of humoral immune responses.

The neonatal immune system is distinct from the immune system of older individuals rendering neonates vulnerable to infections and poor responders to vaccination. Adjuvants can be used as tools to enhance immune responses to co-administered antigens. Antibody (Ab) persistence is mediated by long-lived plasma cells that reside in specialized survival niches in the bone marrow, and transient Ab responses in early life have been associated with decreased survival of plasma cells, possibly due to lack of survival factors. Various cells can secrete these factors and which cells are the main producers is still up for debate, especially in early life where this has not been fully addressed. The receptor BCMA and its ligand APRIL have been shown to be important in the maintenance of plasma cells and Abs. Herein, we assessed age-dependent maturation of a broad range of bone marrow accessory cells and their expression of the survival factors APRIL and IL-6. Furthermore, we performed a comparative analysis of the potential of 5 different adjuvants; LT-K63, mmCT, MF59, IC31 and alum, to enhance expression of survival factors and BCMA following immunization of neonatal mice with tetanus toxoid (TT) vaccine. We found that APRIL expression was reduced in the bone marrow of young mice whereas IL-6 expression was higher. Eosinophils, macrophages, megakaryocytes, monocytes and lymphocytes were important secretors of survival factors in early life but undefined cells also constituted a large fraction of secretors. Immunization and adjuvants enhanced APRIL expression but decreased IL-6 expression in bone marrow cells early after immunization. Furthermore, neonatal immunization with adjuvants enhanced the proportion of plasmablasts and plasma cells that expressed BCMA both in spleen and bone marrow. Enhanced BCMA expression correlated with enhanced vaccine-specific humoral responses, even though the effect of alum on BCMA was less pronounced than those of the other adjuvants at later time points. We propose that low APRIL expression in bone marrow as well as low BCMA expression of plasmablasts/plasma cells in early life together cause transient Ab responses and could represent targets to be triggered by vaccine adjuvants to induce persistent humoral immune responses in this age group.

A comparative study of adjuvants effects on neonatal plasma cell survival niche in bone marrow and persistence of humoral immune responses. The neonatal immune system is distinct from the immune system of older individuals rendering neonates vulnerable to infections and poor responders to vaccination. Adjuvants can be used as tools to enhance immune responses to co-administered antigens. Antibody (Ab) persistence is mediated by long-lived plasma cells that reside in specialized survival niches in the bone marrow, and transient Ab responses in early life have been associated with decreased survival of plasma cells, possibly due to lack of survival factors. Various cells can secrete these factors and which cells are the main producers is still up for debate, especially in early life where this has not been fully addressed. The receptor BCMA and its ligand APRIL have been shown to be important in the maintenance of plasma cells and Abs. Herein, we assessed age-dependent maturation of a broad range of bone marrow accessory cells and their expression of the survival factors APRIL and IL-6. Furthermore, we performed a comparative analysis of the potential of 5 different adjuvants; LT-K63, mmCT, MF59, IC31 and alum, to enhance expression of survival factors and BCMA following immunization of neonatal mice with tetanus toxoid (TT) vaccine. We found that APRIL expression was reduced in the bone marrow of young mice whereas IL-6 expression was higher. Eosinophils, macrophages, megakaryocytes, monocytes and lymphocytes were important secretors of survival factors in early life but undefined cells also constituted a large fraction of secretors. Immunization and adjuvants enhanced APRIL expression but decreased IL-6 expression in bone marrow cells early after immunization. Furthermore, neonatal immunization with adjuvants enhanced the proportion of plasmablasts and plasma cells that expressed BCMA both in spleen and bone marrow. Enhanced BCMA expression correlated with enhanced vaccine-specific humoral responses, even though the effect of alum on BCMA was less pronounced than those of the other adjuvants at later time points. We propose that low APRIL expression in bone marrow as well as low BCMA expression of plasmablasts/plasma cells in early life together cause transient Ab responses and could represent targets to be triggered by vaccine adjuvants to induce persistent humoral immune responses in this age group.

pubmed23n0912_9158

Unsuccessful TB treatment outcomes with a focus on HIV co-infected cases: a cross-sectional retrospective record review in a high-burdened province of South Africa.

South Africa did not meet the MDG targets to reduce TB prevalence and mortality by 50% by 2015, and the TB cure rate remains below the WHO target of 85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co-infected patients are more likely to have unsuccessful TB treatment outcomes. This paper analyses the demographic and clinical characteristics of new TB patients with unsuccessful treatment outcomes, as well as factors associated with unsuccessful treatment outcomes for HIV co-infected patients. A cross-sectional retrospective record review of routinely collected data for new TB cases registered in the Free State provincial electronic TB database between 2009 and 2012. The outcome variable, unsuccessful treatment, was defined as cases ≥15 years that 'died', 'failed' or 'defaulted' as the recorded treatment outcome. The data were subjected to descriptive and logistic regression analyses. From 2009 to 2012 there were 66,940 new TB cases among persons ≥15 years (with a recorded TB treatment outcome), of these 61% were co-infected with HIV. Unsuccessful TB treatment outcomes were recorded for 24.5% of co-infected cases and 15.3% of HIV-negative cases. In 2009, co-infected cases were 2.35 times more at risk for an unsuccessful TB treatment outcome (OR: 2.35; CI: 2.06-2.69); this figure decreased to 1.8 times by 2012 (OR: 1.80; CI: 1.63-1.99). Among the co-infected cases, main risk factors for unsuccessful treatment outcomes were: ≥ 65 years (AOR: 1.71; CI: 1.25-2.35); receiving treatment in healthcare facilities in District D (AOR: 1.15; CI 1.05-1.28); and taking CPT (and not ART) (AOR: 1.28; CI: 1.05-1.57). Females (AOR: 0.93; CI: 0.88-0.99) and cases with a CD4 count &gt;350 (AOR: 0.40; CI: 0.36-0.44) were less likely to have an unsuccessful treatment outcome. The importance of TB-HIV/AIDS treatment integration is evident as co-infected patients on both ART and CPT, and those who have a higher CD4 count are less likely to have an unsuccessful TB treatment outcome. Furthermore, co-infected patients who require more programmatic attention are older people and males.

Unsuccessful TB treatment outcomes with a focus on HIV co-infected cases: a cross-sectional retrospective record review in a high-burdened province of South Africa. South Africa did not meet the MDG targets to reduce TB prevalence and mortality by 50% by 2015, and the TB cure rate remains below the WHO target of 85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co-infected patients are more likely to have unsuccessful TB treatment outcomes. This paper analyses the demographic and clinical characteristics of new TB patients with unsuccessful treatment outcomes, as well as factors associated with unsuccessful treatment outcomes for HIV co-infected patients. A cross-sectional retrospective record review of routinely collected data for new TB cases registered in the Free State provincial electronic TB database between 2009 and 2012. The outcome variable, unsuccessful treatment, was defined as cases ≥15 years that 'died', 'failed' or 'defaulted' as the recorded treatment outcome. The data were subjected to descriptive and logistic regression analyses. From 2009 to 2012 there were 66,940 new TB cases among persons ≥15 years (with a recorded TB treatment outcome), of these 61% were co-infected with HIV. Unsuccessful TB treatment outcomes were recorded for 24.5% of co-infected cases and 15.3% of HIV-negative cases. In 2009, co-infected cases were 2.35 times more at risk for an unsuccessful TB treatment outcome (OR: 2.35; CI: 2.06-2.69); this figure decreased to 1.8 times by 2012 (OR: 1.80; CI: 1.63-1.99). Among the co-infected cases, main risk factors for unsuccessful treatment outcomes were: ≥ 65 years (AOR: 1.71; CI: 1.25-2.35); receiving treatment in healthcare facilities in District D (AOR: 1.15; CI 1.05-1.28); and taking CPT (and not ART) (AOR: 1.28; CI: 1.05-1.57). Females (AOR: 0.93; CI: 0.88-0.99) and cases with a CD4 count &gt;350 (AOR: 0.40; CI: 0.36-0.44) were less likely to have an unsuccessful treatment outcome. The importance of TB-HIV/AIDS treatment integration is evident as co-infected patients on both ART and CPT, and those who have a higher CD4 count are less likely to have an unsuccessful TB treatment outcome. Furthermore, co-infected patients who require more programmatic attention are older people and males.

pubmed23n0019_10808

Cardiopathogenicity of soybean oil and tower rapeseed oil triglycerides when fed to male rats.

The triglycerides of soybean oil were purified by molecular distillation and those of Tower rapeseed oil by molecular distillation and adsorption chromatography. The original oils and the purified triglycerides were incorporated in semisynthetic diets at 20% by weight and fed for 16 weeks to weanling male Sprague-Dawley rats to compare the nutritional and pathological effects of the oils and their triglyceride fractions on rats. The study was carried out at two independent laboratories. No significant differences were observed between the results of the two establishments. The incidence of myocardial lesions was significantly higher in rats fed Tower rapeseed oil than in those fed soybean oil. Purification of the triglycerides by molecular distillation and adsorption chromatography appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity of the test oils to rats resides in the triglycerides of these oils.

Cardiopathogenicity of soybean oil and tower rapeseed oil triglycerides when fed to male rats. The triglycerides of soybean oil were purified by molecular distillation and those of Tower rapeseed oil by molecular distillation and adsorption chromatography. The original oils and the purified triglycerides were incorporated in semisynthetic diets at 20% by weight and fed for 16 weeks to weanling male Sprague-Dawley rats to compare the nutritional and pathological effects of the oils and their triglyceride fractions on rats. The study was carried out at two independent laboratories. No significant differences were observed between the results of the two establishments. The incidence of myocardial lesions was significantly higher in rats fed Tower rapeseed oil than in those fed soybean oil. Purification of the triglycerides by molecular distillation and adsorption chromatography appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity of the test oils to rats resides in the triglycerides of these oils.

pubmed23n0274_2155

Side-chain specificities of human and bovine cytochromes P-450scc.

Cytochrome P-450scc catalyses the conversion of cholesterol to pregnenolone by the sequential hydroxylation of the side chain of cholesterol. This occurs at a single active site and produces 22R-hydroxycholesterol and 22R-20 alpha-dihydroxycholesterol as intermediates. To further define the active site of human and bovine cytochromes P-450scc, we have examined the kinetics of the conversion of structural analogues of cholesterol with modified side chains, to pregnenolone. Analysis of the side-chain cleavage of analogues of cholesterol modified at C22 confirmed the high degree of structural specificity for the 22R position by cytochrome P-450scc, the major effect being on the turnover number (kcat) rather than on binding. The analogues of cholesterol that had a polar group at C24, C25 or C26 had much lower Km values and generally lower kcat values than the non-polar analogues which were tested. Km values of the polar analogues were 3-25-times lower than the Km for cholesterol and kcat values were also much lower than the kcat values for cholesterol, particularly for the human enzyme. The data suggest that the tight binding of the analogues with a hydroxyl or ketone group at C24, C25 or C26 places C20 and C22 in a poor orientation relative to the heme group for hydroxylation to occur. Many of the polar analogues which were tested are postulated regulators of cellular cholesterol metabolism. Several of these analogues are good substrates for bovine and human cytochromes P-450scc at low substrate concentration, as determined from their kcat/Km values. This study also indicates that the active site of cytochrome P-450scc is well conserved between bovine and human cytochromes. However, small species differences are evident since lower kcat values relative to the kcat of cholesterol are observed for some polar side-chain analogues of cholesterol with the human enzyme.

Side-chain specificities of human and bovine cytochromes P-450scc. Cytochrome P-450scc catalyses the conversion of cholesterol to pregnenolone by the sequential hydroxylation of the side chain of cholesterol. This occurs at a single active site and produces 22R-hydroxycholesterol and 22R-20 alpha-dihydroxycholesterol as intermediates. To further define the active site of human and bovine cytochromes P-450scc, we have examined the kinetics of the conversion of structural analogues of cholesterol with modified side chains, to pregnenolone. Analysis of the side-chain cleavage of analogues of cholesterol modified at C22 confirmed the high degree of structural specificity for the 22R position by cytochrome P-450scc, the major effect being on the turnover number (kcat) rather than on binding. The analogues of cholesterol that had a polar group at C24, C25 or C26 had much lower Km values and generally lower kcat values than the non-polar analogues which were tested. Km values of the polar analogues were 3-25-times lower than the Km for cholesterol and kcat values were also much lower than the kcat values for cholesterol, particularly for the human enzyme. The data suggest that the tight binding of the analogues with a hydroxyl or ketone group at C24, C25 or C26 places C20 and C22 in a poor orientation relative to the heme group for hydroxylation to occur. Many of the polar analogues which were tested are postulated regulators of cellular cholesterol metabolism. Several of these analogues are good substrates for bovine and human cytochromes P-450scc at low substrate concentration, as determined from their kcat/Km values. This study also indicates that the active site of cytochrome P-450scc is well conserved between bovine and human cytochromes. However, small species differences are evident since lower kcat values relative to the kcat of cholesterol are observed for some polar side-chain analogues of cholesterol with the human enzyme.

pubmed23n0261_12991

[Tetrahymena pyriformis--a cell test system for environmental medicine. The effect of harmful substances on the cell morphology of Tetrahymena pyriformis].

In the region of Middle Germany phenols and their derivatives are important toxicological compounds for the environment and man. These compounds from wastes water of brown coal mining are source of danger, which can't estimate now. The influence of phenolic compounds on cells and organisms will be investigated with a species of ciliates-Tetrahymena pyriformis as testing system. T. pyriformis is a single-celled eucaryotic organism, which is comparable in sensitiveness and responsiveness to human tissue cells. That's why this cell system is very suitable to investigate on the influence of environmental pollutants. In our investigations phenol and 2,3-Dichlorophenol were used. Both compounds have a very toxic effect on cells. The toxicity of 2,3-Dichlorophenol is 50 times higher than the toxicity of pure phenol. Investigations of vitality by turbidimetry and morphology by image analysis have show that these compounds had an complex of the organisms.

[Tetrahymena pyriformis--a cell test system for environmental medicine. The effect of harmful substances on the cell morphology of Tetrahymena pyriformis]. In the region of Middle Germany phenols and their derivatives are important toxicological compounds for the environment and man. These compounds from wastes water of brown coal mining are source of danger, which can't estimate now. The influence of phenolic compounds on cells and organisms will be investigated with a species of ciliates-Tetrahymena pyriformis as testing system. T. pyriformis is a single-celled eucaryotic organism, which is comparable in sensitiveness and responsiveness to human tissue cells. That's why this cell system is very suitable to investigate on the influence of environmental pollutants. In our investigations phenol and 2,3-Dichlorophenol were used. Both compounds have a very toxic effect on cells. The toxicity of 2,3-Dichlorophenol is 50 times higher than the toxicity of pure phenol. Investigations of vitality by turbidimetry and morphology by image analysis have show that these compounds had an complex of the organisms.

pubmed23n0652_9210

Generation of a dominant-negative glycogen targeting subunit for protein phosphatase-1.

Modulation of the expression of the protein phosphatase-1 (PP1) glycogen-targeting subunit PTG exerts profound effects on cellular glycogen metabolism in vitro and in vivo. PTG contains three distinct binding domains for glycogen, PP1, and a common site for glycogen synthase and phosphorylase. The impact of disrupting the PP1-binding domain on PTG function was examined in 3T3-L1 adipocytes. A full-length PTG mutant was generated as an adenoviral construct in which the valine and phenylalanine residues in the conserved PP1-binding domain were mutated to alanine (PTG-VF). Infection of fully differentiated 3T3-L1 adipocytes with the PTG-VF adenovirus reduced glycogen stores by over 50%. In vitro, PTG-VF competitively interfered with wild-type PTG action, suggesting that the mutant construct acted as a dominant-negative molecule. The reduction in cellular glycogen storage was due to a significantly increased rate of glycogen turnover. Interestingly, acute basal and insulin-stimulated glucose uptake and glycogen synthesis rates were enhanced in PTG-VF expressing cells vs. control 3T3-L1 adipocytes, likely as a compensatory response to the loss of glycogen stores. These results indicate that the mutation of the PP1-binding domain on PTG resulted in the generation of a dominant-negative molecule that impeded endogenous PTG action and reduced cellular glycogen levels, through enhancement of glycogenolysis rather than impairment of glycogen synthesis.

Generation of a dominant-negative glycogen targeting subunit for protein phosphatase-1. Modulation of the expression of the protein phosphatase-1 (PP1) glycogen-targeting subunit PTG exerts profound effects on cellular glycogen metabolism in vitro and in vivo. PTG contains three distinct binding domains for glycogen, PP1, and a common site for glycogen synthase and phosphorylase. The impact of disrupting the PP1-binding domain on PTG function was examined in 3T3-L1 adipocytes. A full-length PTG mutant was generated as an adenoviral construct in which the valine and phenylalanine residues in the conserved PP1-binding domain were mutated to alanine (PTG-VF). Infection of fully differentiated 3T3-L1 adipocytes with the PTG-VF adenovirus reduced glycogen stores by over 50%. In vitro, PTG-VF competitively interfered with wild-type PTG action, suggesting that the mutant construct acted as a dominant-negative molecule. The reduction in cellular glycogen storage was due to a significantly increased rate of glycogen turnover. Interestingly, acute basal and insulin-stimulated glucose uptake and glycogen synthesis rates were enhanced in PTG-VF expressing cells vs. control 3T3-L1 adipocytes, likely as a compensatory response to the loss of glycogen stores. These results indicate that the mutation of the PP1-binding domain on PTG resulted in the generation of a dominant-negative molecule that impeded endogenous PTG action and reduced cellular glycogen levels, through enhancement of glycogenolysis rather than impairment of glycogen synthesis.

pubmed23n0997_24790

Flow Arrest in the Plasma Membrane.

The arrangement of receptors in the plasma membrane strongly affects the ability of a cell to sense its environment both in terms of sensitivity and in terms of spatial resolution. The spatial and temporal arrangement of the receptors is affected in turn by the mechanical properties and the structure of the cell membrane. Here, we focus on characterizing the flow of the membrane in response to the motion of a protein embedded in it. We do so by measuring the correlated diffusion of extracellularly tagged transmembrane neurotrophin receptors TrkB and p75 on transfected neuronal cells. In accord with previous reports, we find that the motion of single receptors exhibits transient confinement to submicron domains. We confirm predictions based on hydrodynamics of fluid membranes, finding long-range correlations in the motion of the receptors in the plasma membrane. However, we discover that these correlations do not persist for long ranges, as predicted, but decay exponentially, with a typical decay length on the scale of the average confining domain size.

Flow Arrest in the Plasma Membrane. The arrangement of receptors in the plasma membrane strongly affects the ability of a cell to sense its environment both in terms of sensitivity and in terms of spatial resolution. The spatial and temporal arrangement of the receptors is affected in turn by the mechanical properties and the structure of the cell membrane. Here, we focus on characterizing the flow of the membrane in response to the motion of a protein embedded in it. We do so by measuring the correlated diffusion of extracellularly tagged transmembrane neurotrophin receptors TrkB and p75 on transfected neuronal cells. In accord with previous reports, we find that the motion of single receptors exhibits transient confinement to submicron domains. We confirm predictions based on hydrodynamics of fluid membranes, finding long-range correlations in the motion of the receptors in the plasma membrane. However, we discover that these correlations do not persist for long ranges, as predicted, but decay exponentially, with a typical decay length on the scale of the average confining domain size.

pubmed23n0984_8946

The magnitude and potential impact of missing data in a sexual violence campus climate survey.

<bObjective:</b Assess the impact of survey non-response and non-completion for a campus climate survey. <bParticipants:</b Intended for all degree-seeking students at a large, public, midwestern university, November 2014. <bMethods:</b The survey covered sexual assault experiences and related attitudes. We identify the magnitude and potential impact of survey non-response by comparing demographic data between respondents and non-respondents, sexual assault prevalence between early and late respondents, and demographic and attitudinal data between survey completers and partial completers. <bResults:</b Demographic groups were differentially represented in the survey. Sexual assault prevalence based on survey results may be underestimated for men, overestimated for women. Sensitive questions did not increase drop-off. Students completing more of the survey differed from those completing less. <bConclusions:</b Colleges must plan survey administration and data sensitivity analysis to reduce potential for bias. Resources for sexual assault-related needs based on estimates from campus climate surveys with high non-response will likely be misallocated.

The magnitude and potential impact of missing data in a sexual violence campus climate survey. <bObjective:</b Assess the impact of survey non-response and non-completion for a campus climate survey. <bParticipants:</b Intended for all degree-seeking students at a large, public, midwestern university, November 2014. <bMethods:</b The survey covered sexual assault experiences and related attitudes. We identify the magnitude and potential impact of survey non-response by comparing demographic data between respondents and non-respondents, sexual assault prevalence between early and late respondents, and demographic and attitudinal data between survey completers and partial completers. <bResults:</b Demographic groups were differentially represented in the survey. Sexual assault prevalence based on survey results may be underestimated for men, overestimated for women. Sensitive questions did not increase drop-off. Students completing more of the survey differed from those completing less. <bConclusions:</b Colleges must plan survey administration and data sensitivity analysis to reduce potential for bias. Resources for sexual assault-related needs based on estimates from campus climate surveys with high non-response will likely be misallocated.

pubmed23n1035_12978

A strawberry accession with elevated methyl anthranilate fruit concentration is naturally resistant to the pest fly Drosophila suzukii.

During the past decade, Drosophila suzukii has established itself as a global invasive fruit pest, enabled by its ability to lay eggs into fresh, ripening fruit. In a previous study, we investigated the impact of different strawberry accessions on the development of D. suzukii eggs, in the search of natural resistance. We identified several accessions that significantly reduced adult fly emergence from infested fruit. In the present study, we aimed at understanding the chemical basis of this effect. We first noted that one of the more resistant accessions showed an unusual enrichment of methyl anthranilate within its fruit, prompting us to investigate this fruit compound as a possible cause limiting fly development. We found that methyl anthranilate alone triggers embryo lethality in a concentration-dependent manner, unlike another comparable organic fruit compound. We also showed that a chemical fraction of the resistant strawberry accession that contains methyl anthranilate carries some activity toward the egg hatching rate. Surprisingly, in spite of the lethal effect of this compound to their eggs, adult females are not only attracted to methyl anthranilate at certain concentrations, but they also display a concentration-dependent preference to lay on substrates enriched in methyl anthranilate. This study demonstrates that methyl anthranilate is a potent agonist molecule against D. suzukii egg development. Its elevated concentration in a specific strawberry accession proven to reduce the fly development may explain, at least in part the fruit resistance. It further illustrates how a single, natural compound, non-toxic to humans could be exploited for biological control of a pest species.

A strawberry accession with elevated methyl anthranilate fruit concentration is naturally resistant to the pest fly Drosophila suzukii. During the past decade, Drosophila suzukii has established itself as a global invasive fruit pest, enabled by its ability to lay eggs into fresh, ripening fruit. In a previous study, we investigated the impact of different strawberry accessions on the development of D. suzukii eggs, in the search of natural resistance. We identified several accessions that significantly reduced adult fly emergence from infested fruit. In the present study, we aimed at understanding the chemical basis of this effect. We first noted that one of the more resistant accessions showed an unusual enrichment of methyl anthranilate within its fruit, prompting us to investigate this fruit compound as a possible cause limiting fly development. We found that methyl anthranilate alone triggers embryo lethality in a concentration-dependent manner, unlike another comparable organic fruit compound. We also showed that a chemical fraction of the resistant strawberry accession that contains methyl anthranilate carries some activity toward the egg hatching rate. Surprisingly, in spite of the lethal effect of this compound to their eggs, adult females are not only attracted to methyl anthranilate at certain concentrations, but they also display a concentration-dependent preference to lay on substrates enriched in methyl anthranilate. This study demonstrates that methyl anthranilate is a potent agonist molecule against D. suzukii egg development. Its elevated concentration in a specific strawberry accession proven to reduce the fly development may explain, at least in part the fruit resistance. It further illustrates how a single, natural compound, non-toxic to humans could be exploited for biological control of a pest species.

pubmed23n0664_2254

The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid photosensitizes the formation of oxidized guanines in cellulo after UV-A or UV-B exposure.

The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) is water soluble and is widely used in the cosmetic industry because it absorbs strongly at UV-B wavelengths. Previous studies have shown that PBSA, photoexcited by UV-B, oxidizes guanine bases in vitro. Because of its potential phototoxic effect, it is important to determine whether PBSA photosensitizes in cellulo the formation of oxidatively generated DNA damage on UV exposure. For this purpose, we investigated, in vitro and in cellulo, the effect of PBSA on DNA bases after UV-A or UV-B irradiation. To monitor the formation of oxidized bases and cyclobutane pyrimidine dimers (CPDs), DNA was digested either with FaPy-DNA glycosylase and endonuclease III or with T4 endonuclease V and photolyase, then analyzed by means of neutral- and glyoxal-agarose gel electrophoresis and ligation-mediated PCR. In cellulo, we found that PBSA provided good protection against CPD formation after UV-B exposure. However, PBSA also photosensitized oxidized guanines on UV-A and UV-B irradiation. Our results indicate that PBSA has the potential to function as a double-edged sword toward DNA and question its suitability for sunscreen applications.

The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid photosensitizes the formation of oxidized guanines in cellulo after UV-A or UV-B exposure. The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) is water soluble and is widely used in the cosmetic industry because it absorbs strongly at UV-B wavelengths. Previous studies have shown that PBSA, photoexcited by UV-B, oxidizes guanine bases in vitro. Because of its potential phototoxic effect, it is important to determine whether PBSA photosensitizes in cellulo the formation of oxidatively generated DNA damage on UV exposure. For this purpose, we investigated, in vitro and in cellulo, the effect of PBSA on DNA bases after UV-A or UV-B irradiation. To monitor the formation of oxidized bases and cyclobutane pyrimidine dimers (CPDs), DNA was digested either with FaPy-DNA glycosylase and endonuclease III or with T4 endonuclease V and photolyase, then analyzed by means of neutral- and glyoxal-agarose gel electrophoresis and ligation-mediated PCR. In cellulo, we found that PBSA provided good protection against CPD formation after UV-B exposure. However, PBSA also photosensitized oxidized guanines on UV-A and UV-B irradiation. Our results indicate that PBSA has the potential to function as a double-edged sword toward DNA and question its suitability for sunscreen applications.

pubmed23n0253_9832

[Phosphofructokinase (PFK)].

This review is aimed to provide the up-to-date knowledge on phosphofructokinase (PFK), a key enzyme of glycolysis, with special references to the recent advances of molecular biology of the enzyme. In human, three isozymes named M (muscle), L (liver) and P (platelet) are identified. Recently, mRNA and gene structures of these isozymes have been clarified. Deficiency of PFK-M is characterized by muscle weakness due to fuel crisis in exercising muscles. Up to now, gene defects of PFK deficient patients have been sought in 38 alleles from Japanese, Ashkenazi Jewish, Non-Ashkenazi Italian, French Canadian and Swiss patients and molecular heterogeneity has been elucidated. Down syndrome, in which trisomy of chromosome 21 is known provides us an interesting gene-dosage effect on PFK-L isozyme. Other various pathologic states affecting PFK activity in vivo are also reviewed briefly.

[Phosphofructokinase (PFK)]. This review is aimed to provide the up-to-date knowledge on phosphofructokinase (PFK), a key enzyme of glycolysis, with special references to the recent advances of molecular biology of the enzyme. In human, three isozymes named M (muscle), L (liver) and P (platelet) are identified. Recently, mRNA and gene structures of these isozymes have been clarified. Deficiency of PFK-M is characterized by muscle weakness due to fuel crisis in exercising muscles. Up to now, gene defects of PFK deficient patients have been sought in 38 alleles from Japanese, Ashkenazi Jewish, Non-Ashkenazi Italian, French Canadian and Swiss patients and molecular heterogeneity has been elucidated. Down syndrome, in which trisomy of chromosome 21 is known provides us an interesting gene-dosage effect on PFK-L isozyme. Other various pathologic states affecting PFK activity in vivo are also reviewed briefly.

pubmed23n1151_12719

The Application Effect of Jiawei Sanyu Shengjing Decoction Combined with High Ligation of the Spermatic Vein in Varicocele Male Infertility Patients.

To analyze the application effect of Jiawei Sanyu Shengjing decoction combined with high ligation of the internal spermatic vein in male infertility patients with varicocele (VC). 106 male infertility patients with VC treated in our hospital from December 2018 to March 2019 were selected as examples. According to the length of stay, they were divided into the control group and observation group, with 53 cases in each group. High ligation of the internal spermatic vein was performed in both groups. On this basis, the observation group was treated with modified Sanyu Shengjing decoction, and the therapeutic effects of the two groups were compared. The effective rate of 94.34% in the observation group was higher than 79.25% in the control group (<iP</i &lt; 0.05). After treatment, the serum index level and sperm deformity rate in the observation group were lower than those in the control group, and the semen density and sperm activity were higher than those in the control group (<iP</i &lt; 0.05). The treatment of VC male infertility with modified Sanyu Shengjing decoction combined with high ligation of the internal spermatic vein can effectively improve the number of sperm and reduce the density of semen.

The Application Effect of Jiawei Sanyu Shengjing Decoction Combined with High Ligation of the Spermatic Vein in Varicocele Male Infertility Patients. To analyze the application effect of Jiawei Sanyu Shengjing decoction combined with high ligation of the internal spermatic vein in male infertility patients with varicocele (VC). 106 male infertility patients with VC treated in our hospital from December 2018 to March 2019 were selected as examples. According to the length of stay, they were divided into the control group and observation group, with 53 cases in each group. High ligation of the internal spermatic vein was performed in both groups. On this basis, the observation group was treated with modified Sanyu Shengjing decoction, and the therapeutic effects of the two groups were compared. The effective rate of 94.34% in the observation group was higher than 79.25% in the control group (<iP</i &lt; 0.05). After treatment, the serum index level and sperm deformity rate in the observation group were lower than those in the control group, and the semen density and sperm activity were higher than those in the control group (<iP</i &lt; 0.05). The treatment of VC male infertility with modified Sanyu Shengjing decoction combined with high ligation of the internal spermatic vein can effectively improve the number of sperm and reduce the density of semen.

pubmed23n0697_1434

Dithiocarbamated chitosan as a potent biopolymer for toxic cation remediation.

The biopolymer chitosan was chemically modified with dithiocarbamate, characterized by elemental analysis, IR, (13)C NMR and TG, and applied for lead, copper and cadmium removal. Based on sulfur elemental analysis an amount of 2.66 mmol g(-1) of pendant chain was incorporated in the original biopolymer, as also demonstrated through the appearance of a signal at 201 ppm in the (13)C NMR in the solid state. The TG curve demonstrated that the final product is more stable than the precursor chitosan. The sorption capacity of modified biopolymer was determined through a batchwise methodology, with maximum capacities of 2.24; 1.14 and 0.84 mmol g(-1) for divalent lead, copper and cadmium from aqueous solution, respectively. The highest sorption capacity for lead reflects the soft cation/sulfur interaction. The experimental data were adjusted to the Langmuir, the Freundlich and the Temkin sorption isotherm models using both linear and nonlinear regression analysis.

Dithiocarbamated chitosan as a potent biopolymer for toxic cation remediation. The biopolymer chitosan was chemically modified with dithiocarbamate, characterized by elemental analysis, IR, (13)C NMR and TG, and applied for lead, copper and cadmium removal. Based on sulfur elemental analysis an amount of 2.66 mmol g(-1) of pendant chain was incorporated in the original biopolymer, as also demonstrated through the appearance of a signal at 201 ppm in the (13)C NMR in the solid state. The TG curve demonstrated that the final product is more stable than the precursor chitosan. The sorption capacity of modified biopolymer was determined through a batchwise methodology, with maximum capacities of 2.24; 1.14 and 0.84 mmol g(-1) for divalent lead, copper and cadmium from aqueous solution, respectively. The highest sorption capacity for lead reflects the soft cation/sulfur interaction. The experimental data were adjusted to the Langmuir, the Freundlich and the Temkin sorption isotherm models using both linear and nonlinear regression analysis.

pubmed23n0943_14649

Evaluation of Lung Function in Liver Transplant Candidates.

A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted.

Evaluation of Lung Function in Liver Transplant Candidates. A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted.

pubmed23n0751_20809

Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity.

Combretastatin A4 analogues were synthesized on steroidal framework from gallic acid with a possibility of anti-breast cancer agents. Twenty two analogues were synthesized and evaluated for cytotoxicity against human breast cancer cell lines (MCF-7 &amp; MDA-MB 231). The best analogue 22 showed potent antitubulin effect. Docking experiments also supported strong binding affinity of 22 to microtubule polymerase. In cell cycle analysis, 22 induced apoptosis in MCF-7 cells significantly. It was found to be non-toxic up to 300 mg/kg dose in Swiss albino mice in acute oral toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".

Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity. Combretastatin A4 analogues were synthesized on steroidal framework from gallic acid with a possibility of anti-breast cancer agents. Twenty two analogues were synthesized and evaluated for cytotoxicity against human breast cancer cell lines (MCF-7 &amp; MDA-MB 231). The best analogue 22 showed potent antitubulin effect. Docking experiments also supported strong binding affinity of 22 to microtubule polymerase. In cell cycle analysis, 22 induced apoptosis in MCF-7 cells significantly. It was found to be non-toxic up to 300 mg/kg dose in Swiss albino mice in acute oral toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".

pubmed23n0593_655

Genotype X diet interactions in mice predisposed to mammary cancer. I. Body weight and fat.

High dietary fat intake and obesity may increase susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F(2) mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F(2) mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe development of the F(2) population (n = 615) which resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)(634Mul), effects of diet on growth and body composition, and QTL and QTL x diet and/or gender interaction effects for growth and obesity-related phenotypes. We identified 38 QTL for body composition traits that were significant at the genome-wide 0.05 level, likely representing nine distinct loci after accounting for pleiotropic effects. QTL x diet and/or gender interactions were present at 15 of these QTL, indicating that such interactions play a significant role in defining the genetic architecture of complex traits such as body weight and obesity.

Genotype X diet interactions in mice predisposed to mammary cancer. I. Body weight and fat. High dietary fat intake and obesity may increase susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F(2) mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F(2) mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe development of the F(2) population (n = 615) which resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)(634Mul), effects of diet on growth and body composition, and QTL and QTL x diet and/or gender interaction effects for growth and obesity-related phenotypes. We identified 38 QTL for body composition traits that were significant at the genome-wide 0.05 level, likely representing nine distinct loci after accounting for pleiotropic effects. QTL x diet and/or gender interactions were present at 15 of these QTL, indicating that such interactions play a significant role in defining the genetic architecture of complex traits such as body weight and obesity.

pubmed23n0312_22205

Interleukin-1beta induced changes in the protein expression of rat islets: a computerized database.

Insulin-dependent diabetes mellitus is caused by an autoimmune destruction of the beta-cells in the islets of Langerhans. The cytokine interleukin 1 inhibits insulin release and is selectively cytotoxic to beta-cells in isolated pancreatic rat islets. The antigen(s) triggering the immune response as well as the intracellular mechanisms of action of interleukin 1-mediated beta-cell cytotoxicity are unknown. However, previous studies have found an association of beta-cell destruction with alterations in protein synthesis. Thus, two-dimensional (2-D) gel electrophoresis of pancreatic islet proteins may be an important tool facilitating studies of the molecular pathogenesis of insulin-dependent diabetes mellitus. 2-D gel electrophoresis of islet proteins may lead to (i) the determination of qualitative and quantitative changes in specific islet proteins induced by cytokines, (ii) the determination of the effects of agents modulating cytokine action, and (iii) the identification of primary islet protein antigen(s) initiating the immune destruction of the beta-cells. Therefore, the aim of this study was to create databases (DB) of all reproducibly detectable protein spots on 10% and 15% acrylamide 2-D gels of neonatal rat islets (10% and 15% DB), labeled under standardized culture conditions. 1235 and 557 spots were present in 5 of 5 gels in the 15% isoelectric focusing (IEF) and nonequilibrium pH gradient electrophoresis (NEPHGE) DB, respectively, whereas 995 and 378 spots were present in 5 of 5 gels in the 10% IEF and NEPHGE DB, respectively, yielding a reproducibility of spot detection between 75.2% and 91.7%. In both DBs, the average coefficient of variation of the percentage of integrated optical density (CV% of %IOD) for spots present in all gels was between 42.4% and 45.7%. When the same sample was analyzed in consecutive sets of gels on different days (interassay analysis), the average CV% of %IOD was 35.5%-36.1%. When the same sample was analyzed repeatedly in one set of gels (intra-assay analysis), the average CV% of %IOD was 30.2% in the IEF gels, while the average CV% of %IOD was 45.7% in the NEPHGE gels. Addition of interleukin-1beta (IL-1beta) to the cultures resulted in statistically significant modulation or de novo synthesis of 105 proteins in the 10% gels. In conclusion, we present the first 10% and 15% acrylamide 2-D gel protein databases of neonatal rat islets of Langerhans and demonstrate its usage to identify proteins altered in expression by IL-1beta.

Interleukin-1beta induced changes in the protein expression of rat islets: a computerized database. Insulin-dependent diabetes mellitus is caused by an autoimmune destruction of the beta-cells in the islets of Langerhans. The cytokine interleukin 1 inhibits insulin release and is selectively cytotoxic to beta-cells in isolated pancreatic rat islets. The antigen(s) triggering the immune response as well as the intracellular mechanisms of action of interleukin 1-mediated beta-cell cytotoxicity are unknown. However, previous studies have found an association of beta-cell destruction with alterations in protein synthesis. Thus, two-dimensional (2-D) gel electrophoresis of pancreatic islet proteins may be an important tool facilitating studies of the molecular pathogenesis of insulin-dependent diabetes mellitus. 2-D gel electrophoresis of islet proteins may lead to (i) the determination of qualitative and quantitative changes in specific islet proteins induced by cytokines, (ii) the determination of the effects of agents modulating cytokine action, and (iii) the identification of primary islet protein antigen(s) initiating the immune destruction of the beta-cells. Therefore, the aim of this study was to create databases (DB) of all reproducibly detectable protein spots on 10% and 15% acrylamide 2-D gels of neonatal rat islets (10% and 15% DB), labeled under standardized culture conditions. 1235 and 557 spots were present in 5 of 5 gels in the 15% isoelectric focusing (IEF) and nonequilibrium pH gradient electrophoresis (NEPHGE) DB, respectively, whereas 995 and 378 spots were present in 5 of 5 gels in the 10% IEF and NEPHGE DB, respectively, yielding a reproducibility of spot detection between 75.2% and 91.7%. In both DBs, the average coefficient of variation of the percentage of integrated optical density (CV% of %IOD) for spots present in all gels was between 42.4% and 45.7%. When the same sample was analyzed in consecutive sets of gels on different days (interassay analysis), the average CV% of %IOD was 35.5%-36.1%. When the same sample was analyzed repeatedly in one set of gels (intra-assay analysis), the average CV% of %IOD was 30.2% in the IEF gels, while the average CV% of %IOD was 45.7% in the NEPHGE gels. Addition of interleukin-1beta (IL-1beta) to the cultures resulted in statistically significant modulation or de novo synthesis of 105 proteins in the 10% gels. In conclusion, we present the first 10% and 15% acrylamide 2-D gel protein databases of neonatal rat islets of Langerhans and demonstrate its usage to identify proteins altered in expression by IL-1beta.

pubmed23n0302_5693

[Effect of infarct size and site, patency of the infarct vessel and perfusion of vital myocardium on remodeling of the left ventricle--studies with cine-magnetic resonance tomography in the first 6 months following myocardial infarct].

Aim of the study was to evaluate the influence of infarct size and location and patency of the infarction and non-infarction vessels on left ventricular morphology and function in the first 6 months after myocardial infarction. 61 patients (17 female, 44 male, 36-83 years) were examined with Cine Magnetic Resonance Imaging (CMRI) 1 and 26 weeks, and with coronary angiography 4 weeks after infarction. 32 patients had anterior, 29 patients posterior myocardial infarction. 15 patients had small infarcts (&lt; 20 gm), 19 intermediate sized (20-40 gm) and 27 patients large infarcts (&gt; 40 gm). CMRI was done in short axis of the left ventricle. Left ventricular enddiastolic and endsystolic volume indices (LVEDVI, LVESVI), ejection fraction (LVEF), muscle mass (VM) and motility (VMOT) of the vital myocardium, mass (IM) and area (IA) of the infarction zone, and volume-mass-ratio (VMR) of the left ventricle were determined on each examination. After 6 months large infarctions had 25% more LVEDVI, 41% more LVESVI, 20% less LVEF, 11% more VM, 13% less VMOT, 13% more IM, 47% more IA, and a 17% increased VMR compared to small infarcts. Anterior infarctions showed 11% more LVEDVI, 19% more LVESVI, 7% less LVEF, 4% more VM, the same VMOT, 5% more IM, 21% more IA, and 6% more VMR than posterior infarctions. If the infarction vessel was not perfused, after 6 months LVEDVI was 12% more, LVESVI 19% more, LVEF 7% smaller, VM 4% less, VMOT the same, IM 5% more, IA 17% more, and VMR 7% more increased than in the group with open infarction artery. When both non-infarction vessels were stenosed, LVEDVI rose 24% more, LVESVI 49% more, LVEF fell 25% more, VM rose 12% more, VMOT fell 26% more, and VMR rose 12% more than in patients with indisturbed perfusion of the vital myocardium. Perfusions of the vital myocardium and infarct size seem to be the most important factors for post infarction remodeling of the left ventricle. Infarct location and patency of the infarction vessel are of less influence.

[Effect of infarct size and site, patency of the infarct vessel and perfusion of vital myocardium on remodeling of the left ventricle--studies with cine-magnetic resonance tomography in the first 6 months following myocardial infarct]. Aim of the study was to evaluate the influence of infarct size and location and patency of the infarction and non-infarction vessels on left ventricular morphology and function in the first 6 months after myocardial infarction. 61 patients (17 female, 44 male, 36-83 years) were examined with Cine Magnetic Resonance Imaging (CMRI) 1 and 26 weeks, and with coronary angiography 4 weeks after infarction. 32 patients had anterior, 29 patients posterior myocardial infarction. 15 patients had small infarcts (&lt; 20 gm), 19 intermediate sized (20-40 gm) and 27 patients large infarcts (&gt; 40 gm). CMRI was done in short axis of the left ventricle. Left ventricular enddiastolic and endsystolic volume indices (LVEDVI, LVESVI), ejection fraction (LVEF), muscle mass (VM) and motility (VMOT) of the vital myocardium, mass (IM) and area (IA) of the infarction zone, and volume-mass-ratio (VMR) of the left ventricle were determined on each examination. After 6 months large infarctions had 25% more LVEDVI, 41% more LVESVI, 20% less LVEF, 11% more VM, 13% less VMOT, 13% more IM, 47% more IA, and a 17% increased VMR compared to small infarcts. Anterior infarctions showed 11% more LVEDVI, 19% more LVESVI, 7% less LVEF, 4% more VM, the same VMOT, 5% more IM, 21% more IA, and 6% more VMR than posterior infarctions. If the infarction vessel was not perfused, after 6 months LVEDVI was 12% more, LVESVI 19% more, LVEF 7% smaller, VM 4% less, VMOT the same, IM 5% more, IA 17% more, and VMR 7% more increased than in the group with open infarction artery. When both non-infarction vessels were stenosed, LVEDVI rose 24% more, LVESVI 49% more, LVEF fell 25% more, VM rose 12% more, VMOT fell 26% more, and VMR rose 12% more than in patients with indisturbed perfusion of the vital myocardium. Perfusions of the vital myocardium and infarct size seem to be the most important factors for post infarction remodeling of the left ventricle. Infarct location and patency of the infarction vessel are of less influence.

pubmed23n0100_10004

In vivo and in vitro development of alpha-MSH and ACTH in the embryonic and postnatal rat brain.

The appearance of immunoreactive alpha-melanotropin (alpha-MSH) and adrenocorticotropin (ACTH) during development was studied in 3 areas of the rat brain--cerebral hemispheres, midbrain and hindbrain--from embryonic day (ED) 13-14 until day 21 postnatally. The alpha-MSH content in vivo was always highest in the midbrain; a peak content at birth was followed by a transient decline and a later, higher plateau from postnatal day 7 onwards. The alpha-MSH content in the cerebral hemispheres rose progressively after birth reaching a peak at day 21. Values in the hindbrain rose at day 3 and changed relatively sue taken at ED 15-16 showed a gradual increase in alpha-MSH content over the 20 days. The alpha-MSH content of hindbrain cultures remained at constant low levels, while no alpha-MSH was detectable in cerebral hemisphere cultures. ACTH appeared in vivo earlier than alpha-MSH and was detectable in embryonic brains at ED 13-14. A transient rise was seen at ED 17-18 and major peaks at birth, day 2 and day 3, in the midbrain, hemispheres and hindbrain, respectively. In vitro, the ACTH content increased in all brain regions during the first 5 days in culture and showed no further change thereafter. Comparisons of the in vivo and in vitro development of alpha-MSH and ACTH demonstrate that (i) these two peptide systems are independent in respect to their localization and time of appearance; (ii) they undergo maturation both in vivo and in vitro; (iii) epigenetic factors, such as interactions with other neurotransmitter systems may modulate the developmental pattern of these two peptides.

In vivo and in vitro development of alpha-MSH and ACTH in the embryonic and postnatal rat brain. The appearance of immunoreactive alpha-melanotropin (alpha-MSH) and adrenocorticotropin (ACTH) during development was studied in 3 areas of the rat brain--cerebral hemispheres, midbrain and hindbrain--from embryonic day (ED) 13-14 until day 21 postnatally. The alpha-MSH content in vivo was always highest in the midbrain; a peak content at birth was followed by a transient decline and a later, higher plateau from postnatal day 7 onwards. The alpha-MSH content in the cerebral hemispheres rose progressively after birth reaching a peak at day 21. Values in the hindbrain rose at day 3 and changed relatively sue taken at ED 15-16 showed a gradual increase in alpha-MSH content over the 20 days. The alpha-MSH content of hindbrain cultures remained at constant low levels, while no alpha-MSH was detectable in cerebral hemisphere cultures. ACTH appeared in vivo earlier than alpha-MSH and was detectable in embryonic brains at ED 13-14. A transient rise was seen at ED 17-18 and major peaks at birth, day 2 and day 3, in the midbrain, hemispheres and hindbrain, respectively. In vitro, the ACTH content increased in all brain regions during the first 5 days in culture and showed no further change thereafter. Comparisons of the in vivo and in vitro development of alpha-MSH and ACTH demonstrate that (i) these two peptide systems are independent in respect to their localization and time of appearance; (ii) they undergo maturation both in vivo and in vitro; (iii) epigenetic factors, such as interactions with other neurotransmitter systems may modulate the developmental pattern of these two peptides.

pubmed23n1005_22580

Consolidation-to-tumor ratio and tumor disappearance ratio are not independent prognostic factors for the patients with resected lung adenocarcinomas.

Our study aimed to investigate the independent prognostic values of consolidation-to-tumor ratio (CTR) and tumor disappearance ratio (TDR) after adjustment for the conventional prognostic factors and the eighth edition clinical T category for patients with resected lung adenocarcinomas. This retrospective study included 691 patients (281 men and 410 women; median age, 63 years) with resected lung adenocarcinomas (clinical T1N0M0). The prognostic implications for disease-free survival (DFS) of CTR and TDR in continuous and categorical forms were analyzed using multivariable-adjusted Cox regression analysis, including multiple clinico-radiological prognostic factors and the clinical T category based on the solid portion measurement. Analysis was performed for the total study population and for two part-solid nodule subgroups (cT1mi/cT1a to cT1c and cT1mi/cT1a to cT1b, respectively). For the total study population, CTR and TDR were not selected in the multivariable Cox regression models, which indicated that these are not independent prognostic factors. Age (adjusted HR: 1.026; P = 0.022) and clinical T category (adjusted HR for cT1b: 3.475; P = 0.019; adjusted HR for cT1c: 9.938; P &lt; 0.001) were independently associated with DFS. For the part-solid nodule subgroups, multivariable-adjusted HRs for CTR and TDR were not statistically significant (all P &gt; 0.05). CTR and TDR were not independent prognostic factors. Preoperative prognostication based on clinical T category would be sufficient without further stratification according to CTR or TDR.

Consolidation-to-tumor ratio and tumor disappearance ratio are not independent prognostic factors for the patients with resected lung adenocarcinomas. Our study aimed to investigate the independent prognostic values of consolidation-to-tumor ratio (CTR) and tumor disappearance ratio (TDR) after adjustment for the conventional prognostic factors and the eighth edition clinical T category for patients with resected lung adenocarcinomas. This retrospective study included 691 patients (281 men and 410 women; median age, 63 years) with resected lung adenocarcinomas (clinical T1N0M0). The prognostic implications for disease-free survival (DFS) of CTR and TDR in continuous and categorical forms were analyzed using multivariable-adjusted Cox regression analysis, including multiple clinico-radiological prognostic factors and the clinical T category based on the solid portion measurement. Analysis was performed for the total study population and for two part-solid nodule subgroups (cT1mi/cT1a to cT1c and cT1mi/cT1a to cT1b, respectively). For the total study population, CTR and TDR were not selected in the multivariable Cox regression models, which indicated that these are not independent prognostic factors. Age (adjusted HR: 1.026; P = 0.022) and clinical T category (adjusted HR for cT1b: 3.475; P = 0.019; adjusted HR for cT1c: 9.938; P &lt; 0.001) were independently associated with DFS. For the part-solid nodule subgroups, multivariable-adjusted HRs for CTR and TDR were not statistically significant (all P &gt; 0.05). CTR and TDR were not independent prognostic factors. Preoperative prognostication based on clinical T category would be sufficient without further stratification according to CTR or TDR.

pubmed23n0912_3520

The anti-inflammatory and antinociceptive activity of albumins from Crotalaria retusa seeds.

Seeds of Crotalaria retusa L. are used in popular medicine because of their pharmacological properties. The albumin fraction obtained from its seeds contains lectin, a protein known to have analgesic and anti-inflammatory properties. Thus, albumins extracted from C. retusa were investigated for their anti-inflammatory and antinociceptive effects. The intraperitoneal administration of different doses of albumins (5, 10 or 20mg/kg) significantly inhibited the mice paw edema induced by carrageenan (maximum inhibition rate of 80.9% at four hours, 20mg/kg), and this event was followed by diminishing paw myeloperoxidase measurements. Albumins (20mg/kg) also inhibited neutrophil migration into the peritoneal cavity induced by carrageenan. However, no effect was observed in the dextran-induced paw edema and abdominal contortions induced by acetic acid. Moreover, albumins (20mg/kg) significantly reduced the second (inflammatory) phase of the licking time induced by formalin. The detection of heammaglutinating activity against human erythrocytes in albumins evidences the presence of lectin in seeds of C. retusa. Our data showed that seeds of C. retusa had anti-inflammatory and antinociceptive properties and such activities are probably due to the inhibitory effect on neutrophil migration of lectin present in albumins.

The anti-inflammatory and antinociceptive activity of albumins from Crotalaria retusa seeds. Seeds of Crotalaria retusa L. are used in popular medicine because of their pharmacological properties. The albumin fraction obtained from its seeds contains lectin, a protein known to have analgesic and anti-inflammatory properties. Thus, albumins extracted from C. retusa were investigated for their anti-inflammatory and antinociceptive effects. The intraperitoneal administration of different doses of albumins (5, 10 or 20mg/kg) significantly inhibited the mice paw edema induced by carrageenan (maximum inhibition rate of 80.9% at four hours, 20mg/kg), and this event was followed by diminishing paw myeloperoxidase measurements. Albumins (20mg/kg) also inhibited neutrophil migration into the peritoneal cavity induced by carrageenan. However, no effect was observed in the dextran-induced paw edema and abdominal contortions induced by acetic acid. Moreover, albumins (20mg/kg) significantly reduced the second (inflammatory) phase of the licking time induced by formalin. The detection of heammaglutinating activity against human erythrocytes in albumins evidences the presence of lectin in seeds of C. retusa. Our data showed that seeds of C. retusa had anti-inflammatory and antinociceptive properties and such activities are probably due to the inhibitory effect on neutrophil migration of lectin present in albumins.

pubmed23n0845_17770

Termite Incidence on an Araucaria Plantation Forest in Teluk Bahang, Penang.

A study was carried out to evaluate the incidence of termite attack on an Araucaria cunninghamii plantation at Teluk Bahang Forest Park (TBFP), Penang. The hilly plantation area was surveyed to determine the diversity of termite species present. Termite specimens were collected from standin Araucaria trees, underground monitoring (aggregation) stations, fallen logs, forest litter and mounds (nests). Seven species of termites were identified from 6 genera; Coptotermes curvignathus, Schedorhinotermes medioobscurus, Schedorhinotermes malaccensis, Odontotermes sarawakensis Parrhinotermes aequalis, Macrotermes malaccensis and Hospitalitermes hospitalis. A total of 289 Araucaria trees were inspected for signs of termite attack. Termite infestation of trees was determined mainly by the presence of mud on the trunk, but particularly around their butts at ground line. The most dominant termite species discovered infesting the Araucaria trees was Coptotermes curvignathus; accountable for 74% of all infestations. Schedorhinotermes medioobscurus and Odontotermes sarawakensis were commonly found infesting dead trees and/or tree stumps. Approximately 21.5% of all Araucaria trees in the plantation forest at Teluk Bahang were infested by termites.

Termite Incidence on an Araucaria Plantation Forest in Teluk Bahang, Penang. A study was carried out to evaluate the incidence of termite attack on an Araucaria cunninghamii plantation at Teluk Bahang Forest Park (TBFP), Penang. The hilly plantation area was surveyed to determine the diversity of termite species present. Termite specimens were collected from standin Araucaria trees, underground monitoring (aggregation) stations, fallen logs, forest litter and mounds (nests). Seven species of termites were identified from 6 genera; Coptotermes curvignathus, Schedorhinotermes medioobscurus, Schedorhinotermes malaccensis, Odontotermes sarawakensis Parrhinotermes aequalis, Macrotermes malaccensis and Hospitalitermes hospitalis. A total of 289 Araucaria trees were inspected for signs of termite attack. Termite infestation of trees was determined mainly by the presence of mud on the trunk, but particularly around their butts at ground line. The most dominant termite species discovered infesting the Araucaria trees was Coptotermes curvignathus; accountable for 74% of all infestations. Schedorhinotermes medioobscurus and Odontotermes sarawakensis were commonly found infesting dead trees and/or tree stumps. Approximately 21.5% of all Araucaria trees in the plantation forest at Teluk Bahang were infested by termites.

pubmed23n0394_16001

Evaluation of the Tg.AC transgenic mouse assay for testing the human carcinogenic potential of pharmaceuticals--practical pointers, mechanistic clues, and new questions.

Transgenic mouse strains with genetic alterations known to play a role in the multistage process of carcinogenesis are being used increasingly as models for evaluating the human carcinogenic potential of chemicals and pharmaceuticals. The Tg.AC transgenic mouse is one of the strains currently being used in such alternative short-term carcinogenicity testing protocols. This review is focused on recent data from studies designed to evaluate this model's ability to discriminate carcinogens from noncarcinogens. Details relating to protocol design that can significantly impact study outcome are described. Data relating to mechanisms of chemical tumor induction in the Tg.AC model are reviewed, and questions have been formulated to encourage research to further guide appropriate future applications of this model.

Evaluation of the Tg.AC transgenic mouse assay for testing the human carcinogenic potential of pharmaceuticals--practical pointers, mechanistic clues, and new questions. Transgenic mouse strains with genetic alterations known to play a role in the multistage process of carcinogenesis are being used increasingly as models for evaluating the human carcinogenic potential of chemicals and pharmaceuticals. The Tg.AC transgenic mouse is one of the strains currently being used in such alternative short-term carcinogenicity testing protocols. This review is focused on recent data from studies designed to evaluate this model's ability to discriminate carcinogens from noncarcinogens. Details relating to protocol design that can significantly impact study outcome are described. Data relating to mechanisms of chemical tumor induction in the Tg.AC model are reviewed, and questions have been formulated to encourage research to further guide appropriate future applications of this model.

pubmed23n1023_1578

LncRNA LEF1-AS1 Promotes Ovarian Cancer Development Through Interacting with miR-1285-3p.

Growing evidence indicates that long noncoding RNA (lncRNA) is a group of important regulator in cancer development. However, the correlation between lncRNA and ovarian cancer remains elusive. Here, we aimed to investigate the roles of LEF1-AS1 in ovarian cancer progression. LEF1-AS1 expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Survival rate was analyzed by Kaplan-Meier method. Cell Counting Kit-8 (CCK8) and colony formation assays were used for proliferation analysis. Transwell assay was utilized for analyses of migration and invasion. Luciferase reporter assay was performed to test the interaction between LEF1-AS1 and miR-1285-3p. We showed that LEF1-AS1 expression was upregulated in ovarian cancer tissues compared with normal tissues. Besides, LEF1-AS1 level was positively correlated with lymph node metastasis and advanced stage. Enhanced expression of LEF1-AS1 may predict a poor prognosis. Moreover, LEF1-AS1 knockdown suppressed ovarian cancer cell proliferation, migration and invasion. Mechanistically, LEF1-AS1 exerted its oncogenic functions through interacting with miR-1285-3p to inhibit miRNA activity. Rescue assay validated that miR-1285-3p inhibitors abrogated LEF1-AS1-silencer-caused suppression of ovarian cancer progression. Our study revealed that LEF1-AS1 acts as a vital regulation in ovarian cancer progression.

LncRNA LEF1-AS1 Promotes Ovarian Cancer Development Through Interacting with miR-1285-3p. Growing evidence indicates that long noncoding RNA (lncRNA) is a group of important regulator in cancer development. However, the correlation between lncRNA and ovarian cancer remains elusive. Here, we aimed to investigate the roles of LEF1-AS1 in ovarian cancer progression. LEF1-AS1 expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Survival rate was analyzed by Kaplan-Meier method. Cell Counting Kit-8 (CCK8) and colony formation assays were used for proliferation analysis. Transwell assay was utilized for analyses of migration and invasion. Luciferase reporter assay was performed to test the interaction between LEF1-AS1 and miR-1285-3p. We showed that LEF1-AS1 expression was upregulated in ovarian cancer tissues compared with normal tissues. Besides, LEF1-AS1 level was positively correlated with lymph node metastasis and advanced stage. Enhanced expression of LEF1-AS1 may predict a poor prognosis. Moreover, LEF1-AS1 knockdown suppressed ovarian cancer cell proliferation, migration and invasion. Mechanistically, LEF1-AS1 exerted its oncogenic functions through interacting with miR-1285-3p to inhibit miRNA activity. Rescue assay validated that miR-1285-3p inhibitors abrogated LEF1-AS1-silencer-caused suppression of ovarian cancer progression. Our study revealed that LEF1-AS1 acts as a vital regulation in ovarian cancer progression.

pubmed23n0681_11600

Low prevalence of classical galactosemia in Korean population.

This study described the clinical and molecular genetic features of classical galactosemia in Korean population to contribute to the insight in the spectrum of galactosemia in the world, as little is known about the spectrum and incidence of galactosemia in Asia. During the 11-year study period, only three Korean children were identified as having classical galactosemia on the basis of the enzymatic and molecular genetic analysis. Asians have been reported to have mutations distinct from those of Caucasians and African Americans, indicating that galactose-1-phosphate uridyltransferase mutations are ethnically diverse. Our three patients had a total of three mutations (c.252+1G &gt; A, p.Q169H and p.E363K), two of which were novel (p.E363K and c.252+1G &gt; A) mutations. Interestingly, c.252+1G &gt; A, which leads to skipping of exon 2, was observed in all three patients (three of six alleles), indicating that this mutation may be common in Koreans with classical galactosemia. Screening for classical galactosemia in 158,126 Korean newborns identified no patient with classical galactosemia. In conclusion, our findings provide further evidence for the ethnic diversity of classical galactosemia, which may be as rare in Koreans as in other Asian populations.

Low prevalence of classical galactosemia in Korean population. This study described the clinical and molecular genetic features of classical galactosemia in Korean population to contribute to the insight in the spectrum of galactosemia in the world, as little is known about the spectrum and incidence of galactosemia in Asia. During the 11-year study period, only three Korean children were identified as having classical galactosemia on the basis of the enzymatic and molecular genetic analysis. Asians have been reported to have mutations distinct from those of Caucasians and African Americans, indicating that galactose-1-phosphate uridyltransferase mutations are ethnically diverse. Our three patients had a total of three mutations (c.252+1G &gt; A, p.Q169H and p.E363K), two of which were novel (p.E363K and c.252+1G &gt; A) mutations. Interestingly, c.252+1G &gt; A, which leads to skipping of exon 2, was observed in all three patients (three of six alleles), indicating that this mutation may be common in Koreans with classical galactosemia. Screening for classical galactosemia in 158,126 Korean newborns identified no patient with classical galactosemia. In conclusion, our findings provide further evidence for the ethnic diversity of classical galactosemia, which may be as rare in Koreans as in other Asian populations.

pubmed23n0374_23405

Intrapallidal dopamine restores motor deficits induced by 6-hydroxydopamine in the rat.

To explore whether dopamine deficits in the globus pallidus have a role in generating the motor symptoms of Parkinson's disease, we examined the effects of selective intrapallidal administration of dopamine or its antagonists in rats unilaterally lesioned with 6-hydroxydopamine into the medial forebrain bundle. Either the turning behavior induced by apomorphine or the deficit in the performance of a skilled forelimb-reaching task was used as assay for drug action. Microinjection of either the D2 receptor antagonist, sulpiride, or the D1 receptor antagonist, SCH-23390, into the dopamine-denervated pallidum significantly reduced apomorphine induced turning. In animals trained to perform a skilled forelimb-reaching task, 6-OHDA lesions caused a marked motor deficit in the contralateral forelimb. Intrapallidal dopamine applied either intermittently or continuously, restored up to 50% of the motor performance. Continuous application promoted a motor recovery that outlasted dopamine administration. These results show that lack of dopamine in the GP plays an important role in generating the motor symptoms caused by lesion of dopaminergic pathways. Moreover, motor recovery was produced by selectively injecting dopamine into the globus pallidus.

Intrapallidal dopamine restores motor deficits induced by 6-hydroxydopamine in the rat. To explore whether dopamine deficits in the globus pallidus have a role in generating the motor symptoms of Parkinson's disease, we examined the effects of selective intrapallidal administration of dopamine or its antagonists in rats unilaterally lesioned with 6-hydroxydopamine into the medial forebrain bundle. Either the turning behavior induced by apomorphine or the deficit in the performance of a skilled forelimb-reaching task was used as assay for drug action. Microinjection of either the D2 receptor antagonist, sulpiride, or the D1 receptor antagonist, SCH-23390, into the dopamine-denervated pallidum significantly reduced apomorphine induced turning. In animals trained to perform a skilled forelimb-reaching task, 6-OHDA lesions caused a marked motor deficit in the contralateral forelimb. Intrapallidal dopamine applied either intermittently or continuously, restored up to 50% of the motor performance. Continuous application promoted a motor recovery that outlasted dopamine administration. These results show that lack of dopamine in the GP plays an important role in generating the motor symptoms caused by lesion of dopaminergic pathways. Moreover, motor recovery was produced by selectively injecting dopamine into the globus pallidus.

pubmed23n0246_13527

Exercise testing before and after hip arthroplasty.

In 30 elderly women awaiting hip arthroplasty on account of unilateral osteoarthritis of the hip, walking speed and oxygen consumption were measured during a 12-minute test and the power output was calculated from the stair climbing rate. The results were compared with those for a group of 30 normal women of similar age. An age-related decline in maximal walking speed was observed in both groups. After arthroplasty there was a significant increase in maximal walking speed, particularly among the more disabled patients, with the major gain occurring by three months and a further slight increase by six months. Oxygen consumption returned towards normal values, and both stride length and cadence increased by a comparable degree. Mean power output during stair climbing doubled, and both before and after arthroplasty bore a linear relationship to the maximal walking speed.

Exercise testing before and after hip arthroplasty. In 30 elderly women awaiting hip arthroplasty on account of unilateral osteoarthritis of the hip, walking speed and oxygen consumption were measured during a 12-minute test and the power output was calculated from the stair climbing rate. The results were compared with those for a group of 30 normal women of similar age. An age-related decline in maximal walking speed was observed in both groups. After arthroplasty there was a significant increase in maximal walking speed, particularly among the more disabled patients, with the major gain occurring by three months and a further slight increase by six months. Oxygen consumption returned towards normal values, and both stride length and cadence increased by a comparable degree. Mean power output during stair climbing doubled, and both before and after arthroplasty bore a linear relationship to the maximal walking speed.

pubmed23n0297_20929

Management of speech and language disorders in a mental illness unit.

Few speech and language therapists work with psychiatric patients. This study investigates how the specific communication problems of this population are addressed by care staff. Following a survey to determine the prevalence of speech and language problems in a psychiatric population, subjects assessed as having moderate or severe difficulties were selected for further study in order to investigate how they were currently being managed by the people responsible for their care. Key workers or charge nurses were interviewed, and ward and department nursing care plans were examined for mentions of speech and language problems, for aims in connection with these problems and for strategies to achieve these aims. Speech and language problems were not mentioned in 40% of the nursing care plans inspected. Where speech and language problems were mentioned there were aims in connection with half of these and strategies to achieve the aims in only 10% of the sample. The reasons for failure to mention speech and language in nursing care plans and for discrepancies between the results of speech and language therapy assessment and assessments of ward and department staff are discussed.

Management of speech and language disorders in a mental illness unit. Few speech and language therapists work with psychiatric patients. This study investigates how the specific communication problems of this population are addressed by care staff. Following a survey to determine the prevalence of speech and language problems in a psychiatric population, subjects assessed as having moderate or severe difficulties were selected for further study in order to investigate how they were currently being managed by the people responsible for their care. Key workers or charge nurses were interviewed, and ward and department nursing care plans were examined for mentions of speech and language problems, for aims in connection with these problems and for strategies to achieve these aims. Speech and language problems were not mentioned in 40% of the nursing care plans inspected. Where speech and language problems were mentioned there were aims in connection with half of these and strategies to achieve the aims in only 10% of the sample. The reasons for failure to mention speech and language in nursing care plans and for discrepancies between the results of speech and language therapy assessment and assessments of ward and department staff are discussed.

pubmed23n0275_12932

Characterization of the three-dimensional solution structure of human profilin: 1H, 13C, and 15N NMR assignments and global folding pattern.

Human profilin is a 15-kDa protein that plays a major role in the signaling pathway leading to cytoskeletal rearrangement. Essentially complete assignment of the 1H, 13C, and 15N resonances of human profilin have been made by analysis of multidimensional, double- and triple-resonance nuclear magnetic resonance (NMR) experiments. The deviation of the 13C alpha and 13C beta chemical shifts from their respective random coil values were analyzed and correlate well with the secondary structure determined from the NMR data. Twenty structures of human profilin were refined in the program X-PLOR using a total of 1186 experimentally derived conformational restraints. The structures converged to a root mean squared distance deviation of 1.5 A for the backbone atoms. The resultant conformational ensemble indicates that human profilin is an alpha/beta protein comprised of a seven-stranded, antiparallel beta-sheet and three helices. The secondary structure elements for human profilin are quite similar to those found in Acanthamoeba profilin I [Archer, S. J., Vinson, V. K., Pollard, T. D., &amp; Torchia, D. A. (1993), Biochemistry 32, 6680-6687], suggesting that the three-dimensional structure of Acanthamoeba profilin I should be analogous to that determined here for human profilin. The structure determination of human profilin has facilitated the sequence alignment of lower eukaryotic and human profilins and provides a framework upon which the various functionalities of profilin can be explored. At least one element of the actin-binding region of human profilin is an alpha-helix. Two mechanisms by which phosphatidylinositol 4,5-bisphosphate can interfere with actin-binding by human profilin are proposed.

Characterization of the three-dimensional solution structure of human profilin: 1H, 13C, and 15N NMR assignments and global folding pattern. Human profilin is a 15-kDa protein that plays a major role in the signaling pathway leading to cytoskeletal rearrangement. Essentially complete assignment of the 1H, 13C, and 15N resonances of human profilin have been made by analysis of multidimensional, double- and triple-resonance nuclear magnetic resonance (NMR) experiments. The deviation of the 13C alpha and 13C beta chemical shifts from their respective random coil values were analyzed and correlate well with the secondary structure determined from the NMR data. Twenty structures of human profilin were refined in the program X-PLOR using a total of 1186 experimentally derived conformational restraints. The structures converged to a root mean squared distance deviation of 1.5 A for the backbone atoms. The resultant conformational ensemble indicates that human profilin is an alpha/beta protein comprised of a seven-stranded, antiparallel beta-sheet and three helices. The secondary structure elements for human profilin are quite similar to those found in Acanthamoeba profilin I [Archer, S. J., Vinson, V. K., Pollard, T. D., &amp; Torchia, D. A. (1993), Biochemistry 32, 6680-6687], suggesting that the three-dimensional structure of Acanthamoeba profilin I should be analogous to that determined here for human profilin. The structure determination of human profilin has facilitated the sequence alignment of lower eukaryotic and human profilins and provides a framework upon which the various functionalities of profilin can be explored. At least one element of the actin-binding region of human profilin is an alpha-helix. Two mechanisms by which phosphatidylinositol 4,5-bisphosphate can interfere with actin-binding by human profilin are proposed.

pubmed23n1059_938

Impact of secondhand smoke exposure on cognitive function among middle-aged and older women in China: findings from three waves of the China Health and Retirement Longitudinal Study.

To examine the association between secondhand smoke (SSH) and women's global cognitive function and cognitive subdomains. Cohort study. Data for this study were obtained from the China Health and Retirement Longitudinal Study (2011-2013-2015), and pooled analysis was applied to wave 1 and wave 2 (2011-2013), wave 2 and wave 3 (2013-2015) and wave 1 and wave 3 (2011-2015). Data from a total of 6875 Chinese women with normal cognitive function at baseline were selected for analysis, including 2981 who were interviewed in 2011, 2471 in 2013, and 1894 in 2015. SHS was classified based on the number of exposed years (&lt;25 years, ≥25 years to &lt;30 years, ≥30 years to &lt;40 years, ≥40 years). Global cognitive function, visuospatial ability, orientation and attention, and episodic memory function were used as measures of cognitive function. Three waves of data were pooled using a dummy variable to differentiate between 2-year and 4-year groups. LDV models were used to examine independent associations between SHS and cognitive function. Demographic factors, socioeconomic factors, baseline cognitive functioning and health conditions were controlled for in our models. SSH was found to be inversely and significantly associated with cognitive function. Compared with those who had not been exposed to household SSH, women who had lived with a smoking husband had a significantly faster cognition decline, especially in global cognitive function (β=-0.33, 95% CI=-0.66 to -0.01, p&lt;0.01), visuospatial ability (β=-0.04, 95% CI=-0.08 to -0.01, p&lt;0.05) and episodic memory function (β=-0.16, 95% CI=-0.31 to -0.01, p=0.031). Household SSH exposure for more than 40 years was associated with a more significant decline in global cognitive function, visuospatial ability and episodic memory function, but not in orientation and attention function among older Chinese women.

Impact of secondhand smoke exposure on cognitive function among middle-aged and older women in China: findings from three waves of the China Health and Retirement Longitudinal Study. To examine the association between secondhand smoke (SSH) and women's global cognitive function and cognitive subdomains. Cohort study. Data for this study were obtained from the China Health and Retirement Longitudinal Study (2011-2013-2015), and pooled analysis was applied to wave 1 and wave 2 (2011-2013), wave 2 and wave 3 (2013-2015) and wave 1 and wave 3 (2011-2015). Data from a total of 6875 Chinese women with normal cognitive function at baseline were selected for analysis, including 2981 who were interviewed in 2011, 2471 in 2013, and 1894 in 2015. SHS was classified based on the number of exposed years (&lt;25 years, ≥25 years to &lt;30 years, ≥30 years to &lt;40 years, ≥40 years). Global cognitive function, visuospatial ability, orientation and attention, and episodic memory function were used as measures of cognitive function. Three waves of data were pooled using a dummy variable to differentiate between 2-year and 4-year groups. LDV models were used to examine independent associations between SHS and cognitive function. Demographic factors, socioeconomic factors, baseline cognitive functioning and health conditions were controlled for in our models. SSH was found to be inversely and significantly associated with cognitive function. Compared with those who had not been exposed to household SSH, women who had lived with a smoking husband had a significantly faster cognition decline, especially in global cognitive function (β=-0.33, 95% CI=-0.66 to -0.01, p&lt;0.01), visuospatial ability (β=-0.04, 95% CI=-0.08 to -0.01, p&lt;0.05) and episodic memory function (β=-0.16, 95% CI=-0.31 to -0.01, p=0.031). Household SSH exposure for more than 40 years was associated with a more significant decline in global cognitive function, visuospatial ability and episodic memory function, but not in orientation and attention function among older Chinese women.

pubmed23n0014_5671

Limbic and prefrontal contributions to somesthetic learning in monkeys.

Monkeys with forebrain commissurotomies and either lateral temporal, medial temporal, dorsal prefrontal, or ventral prefrontal removals from the right hemisphere were compared with control animals in learning tactual discriminations and reversal with the left hand. The lateral temporal removal yielded no effect, confirming the modality-specific roles of this sector in audition (superior temporal gyrus) and vision (inferior temporal gyrus). The dorsal prefrontal removed yielded a deficit in discrimination learning, possibly as a result of the contralateral sensory neglect or the spatial disorder produced by this lesion. Each of the two remaining lesions, medial temporal and ventral prefrontal, yielded deficits in both discrimination learning and reversal; and the effects of combined removal of these two limbic sectors appeared to be additive. Taken together with earlier findings in vision and audition, the results indicate that the two limbic sectors contribute to learning in all sensory modalities, and that they do so through cortico-cortical interaction with the sensory systems.

Limbic and prefrontal contributions to somesthetic learning in monkeys. Monkeys with forebrain commissurotomies and either lateral temporal, medial temporal, dorsal prefrontal, or ventral prefrontal removals from the right hemisphere were compared with control animals in learning tactual discriminations and reversal with the left hand. The lateral temporal removal yielded no effect, confirming the modality-specific roles of this sector in audition (superior temporal gyrus) and vision (inferior temporal gyrus). The dorsal prefrontal removed yielded a deficit in discrimination learning, possibly as a result of the contralateral sensory neglect or the spatial disorder produced by this lesion. Each of the two remaining lesions, medial temporal and ventral prefrontal, yielded deficits in both discrimination learning and reversal; and the effects of combined removal of these two limbic sectors appeared to be additive. Taken together with earlier findings in vision and audition, the results indicate that the two limbic sectors contribute to learning in all sensory modalities, and that they do so through cortico-cortical interaction with the sensory systems.

pubmed23n0269_19657

Comparative studies of Trypanosoma (Duttonella) vivax isolates from Colombia.

The characterization of four Trypanosoma vivax isolates from Colombia in South America showed that although minor phenotypic differences existed between them, these parasites are antigenically related and belong to a single serodeme. Characterization by isoenzyme assay, karyotyping and DNA probe analysis, showed the Colombian isolates to be more similar to the West African than to Kenyan T. vivax. There was, however, little serological cross-reactivity between South American and African groups of T. vivax. Although the T. vivax isolates from Colombia were pathogenic for dairy calves which showed the typical sign of progressive emaciation, these parasites failed to infect mice or tsetse and could not be cultivated as bloodstream forms in vitro. This study represents initial attempts to establish the phenotypic and serological diversity amongst T. vivax isolates from South America.

Comparative studies of Trypanosoma (Duttonella) vivax isolates from Colombia. The characterization of four Trypanosoma vivax isolates from Colombia in South America showed that although minor phenotypic differences existed between them, these parasites are antigenically related and belong to a single serodeme. Characterization by isoenzyme assay, karyotyping and DNA probe analysis, showed the Colombian isolates to be more similar to the West African than to Kenyan T. vivax. There was, however, little serological cross-reactivity between South American and African groups of T. vivax. Although the T. vivax isolates from Colombia were pathogenic for dairy calves which showed the typical sign of progressive emaciation, these parasites failed to infect mice or tsetse and could not be cultivated as bloodstream forms in vitro. This study represents initial attempts to establish the phenotypic and serological diversity amongst T. vivax isolates from South America.

pubmed23n1023_7816

Multidetector Computed Tomography in Traumatic and Nontraumatic Aortic Emergencies: Emphasis on Acute Aortic Syndromes.

Aortic emergencies comprise of a list of conditions which are uncommon but are potentially fatal. Prognosis is usually determined by emergent diagnosis and treatment and hence radiology plays a key role in patient management. In this article, we aim to review the various causes of aortic emergencies and the relevant imaging findings placing special emphasis on acute aortic syndromes.

Multidetector Computed Tomography in Traumatic and Nontraumatic Aortic Emergencies: Emphasis on Acute Aortic Syndromes. Aortic emergencies comprise of a list of conditions which are uncommon but are potentially fatal. Prognosis is usually determined by emergent diagnosis and treatment and hence radiology plays a key role in patient management. In this article, we aim to review the various causes of aortic emergencies and the relevant imaging findings placing special emphasis on acute aortic syndromes.

pubmed23n1109_8549

B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis.

We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA). We analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4<sup+</supIL23R<sup+</supIL17A<sup+</sup) and Treg cells (CD4<sup+</supCD25<suphi</supFoxP3<sup+</sup) were evaluated flow-cytometrically. Th17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4<sup+</sup cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (-) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033). RTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (-) patients with RA.

B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis. We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA). We analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4<sup+</supIL23R<sup+</supIL17A<sup+</sup) and Treg cells (CD4<sup+</supCD25<suphi</supFoxP3<sup+</sup) were evaluated flow-cytometrically. Th17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4<sup+</sup cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (-) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033). RTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (-) patients with RA.

pubmed23n1081_12049

Creating a platform to enable collaborative learning in One Health: The Joint Initiative for Teaching and Learning on Global Health Challenges and One Health experience.

The "Joint Initiative for Teaching and Learning on Global Health Challenges and One Health" targets education and training in Global Health Challenges and One Health, focusing on surpassing issues that affect One Health training programs. The present work describes the planning, implementation, and challenges to develop an international educational initiative among six partner institutions from four different countries, to build a collaborative teaching and learning environment. The course applies collaborative online international learning principles and is addressed to graduate students of universities from Brazil, Germany, Mozambique, and Kosovo. A pilot curriculum was developed with modules on intercultural competence, interprofessional and collaborative practice in One Health; One Health; healthcare, surveillance, and One Health; bioethics in One Health and careers in Global Health. The course combines synchronous and asynchronous activities developed in groups by mixing students from different institutions and countries. Forty-four experts from 22 institutions of the Americas, Africa, Europe, and Asia collaborated with the course content. Some challenges to implementing the course were the different criteria to assign credits across institutions, the lack of bibliographic material across all partners, limited overlap hours and periods for synchronous activities, and short semester overlap across institutions. Despite the challenges for implementation, the entire process of planning and delivering the course involves intense international collaboration, contributing to the curriculum internationalization, benefiting all institutions involved, promoting exchange even in the challenging scenario of the pandemic of coronavirus disease 2019 (COVID-19).

Creating a platform to enable collaborative learning in One Health: The Joint Initiative for Teaching and Learning on Global Health Challenges and One Health experience. The "Joint Initiative for Teaching and Learning on Global Health Challenges and One Health" targets education and training in Global Health Challenges and One Health, focusing on surpassing issues that affect One Health training programs. The present work describes the planning, implementation, and challenges to develop an international educational initiative among six partner institutions from four different countries, to build a collaborative teaching and learning environment. The course applies collaborative online international learning principles and is addressed to graduate students of universities from Brazil, Germany, Mozambique, and Kosovo. A pilot curriculum was developed with modules on intercultural competence, interprofessional and collaborative practice in One Health; One Health; healthcare, surveillance, and One Health; bioethics in One Health and careers in Global Health. The course combines synchronous and asynchronous activities developed in groups by mixing students from different institutions and countries. Forty-four experts from 22 institutions of the Americas, Africa, Europe, and Asia collaborated with the course content. Some challenges to implementing the course were the different criteria to assign credits across institutions, the lack of bibliographic material across all partners, limited overlap hours and periods for synchronous activities, and short semester overlap across institutions. Despite the challenges for implementation, the entire process of planning and delivering the course involves intense international collaboration, contributing to the curriculum internationalization, benefiting all institutions involved, promoting exchange even in the challenging scenario of the pandemic of coronavirus disease 2019 (COVID-19).

pubmed23n0636_12692

Review article: Effectiveness of patient care teams and the role of clinical expertise and coordination: a literature review.

Health care is increasingly provided by teams of health professionals rather than by individual doctors. For decision makers, it is imperative to identify the critical elements for effective teams to transform health care workplaces into effective team-based environments. The authors reviewed the research literature published between 1990 and February 2008. The available research indicated that teams with enhanced clinical expertise improved professional performance and had mixed effects on patient outcomes. Teams with improved coordination had some positive effects on patient outcomes and limited effects on costs and resource utilization. The combination of enhanced expertise and coordination only showed some limited effect on patient outcomes. The authors conclude that enhancement of the clinical expertise is a potentially effective component of improving the impact of patient care teams. The added value of coordination functions remained unclear. Overall, current studies provide little insight into the underlying mechanisms of teamwork.

Review article: Effectiveness of patient care teams and the role of clinical expertise and coordination: a literature review. Health care is increasingly provided by teams of health professionals rather than by individual doctors. For decision makers, it is imperative to identify the critical elements for effective teams to transform health care workplaces into effective team-based environments. The authors reviewed the research literature published between 1990 and February 2008. The available research indicated that teams with enhanced clinical expertise improved professional performance and had mixed effects on patient outcomes. Teams with improved coordination had some positive effects on patient outcomes and limited effects on costs and resource utilization. The combination of enhanced expertise and coordination only showed some limited effect on patient outcomes. The authors conclude that enhancement of the clinical expertise is a potentially effective component of improving the impact of patient care teams. The added value of coordination functions remained unclear. Overall, current studies provide little insight into the underlying mechanisms of teamwork.

pubmed23n0878_5693

Wearable Sensors for eLearning of Manual Tasks: Using Forearm EMG in Hand Hygiene Training.

In this paper, we propose a novel approach to eLearning that makes use of smart wearable sensors. Traditional eLearning supports the remote and mobile learning of mostly theoretical knowledge. Here we discuss the possibilities of eLearning to support the training of manual skills. We employ forearm armbands with inertial measurement units and surface electromyography sensors to detect and analyse the user's hand motions and evaluate their performance. Hand hygiene is chosen as the example activity, as it is a highly standardized manual task that is often not properly executed. The World Health Organization guidelines on hand hygiene are taken as a model of the optimal hygiene procedure, due to their algorithmic structure. Gesture recognition procedures based on artificial neural networks and hidden Markov modeling were developed, achieving recognition rates of 98 . 30 % ( ± 1 . 26 % ) for individual gestures. Our approach is shown to be promising for further research and application in the mobile eLearning of manual skills.

Wearable Sensors for eLearning of Manual Tasks: Using Forearm EMG in Hand Hygiene Training. In this paper, we propose a novel approach to eLearning that makes use of smart wearable sensors. Traditional eLearning supports the remote and mobile learning of mostly theoretical knowledge. Here we discuss the possibilities of eLearning to support the training of manual skills. We employ forearm armbands with inertial measurement units and surface electromyography sensors to detect and analyse the user's hand motions and evaluate their performance. Hand hygiene is chosen as the example activity, as it is a highly standardized manual task that is often not properly executed. The World Health Organization guidelines on hand hygiene are taken as a model of the optimal hygiene procedure, due to their algorithmic structure. Gesture recognition procedures based on artificial neural networks and hidden Markov modeling were developed, achieving recognition rates of 98 . 30 % ( ± 1 . 26 % ) for individual gestures. Our approach is shown to be promising for further research and application in the mobile eLearning of manual skills.

pubmed23n0631_21668

Determination of tannic acid in industrial wastewater based on chemiluminescence system of KIO₄-H₂O₂-Tween40.

The oxidation reaction of H₂O₂ with KIO₄ can produce chemiluminescence (CL) in the presence of the surfactant Tween40 and the CL intensity of the CL system KIO₄-H₂O₂-Tween40 can be strikingly enhanced after injection of tannic acid. On this basis, a flow injection method with CL detection was established for the determination of tannic acid. The method is simple, rapid and effective to determine tannic acid in the range of 7.0 × 10(-9) to 1.0 × 10(-5) mol/L with a determination limit of 2.3 × 10(-9) mol/L. The relative standard deviation is 2.6% for the determination of 5.0 × 10(-6 )mol/L tannic acid (n = 11). The method has been applied to determine the content of tannic acid in industrial wastewater with satisfactory results. It is believed that the CL reaction formed singlet oxygen (1)O(2)* and the emission was from an excited oxygen molecular pair O₂(¹Δ(g))O₂(¹∑⁻(g)) in the KIO₄-H₂O₂-Tween40 reaction. Tween40 played an important role in enhancing stabilization of the excited oxygen molecular pair O₂(¹Δ(g))O₂(¹∑⁻(g)) and in increasing CL intensity.

Determination of tannic acid in industrial wastewater based on chemiluminescence system of KIO₄-H₂O₂-Tween40. The oxidation reaction of H₂O₂ with KIO₄ can produce chemiluminescence (CL) in the presence of the surfactant Tween40 and the CL intensity of the CL system KIO₄-H₂O₂-Tween40 can be strikingly enhanced after injection of tannic acid. On this basis, a flow injection method with CL detection was established for the determination of tannic acid. The method is simple, rapid and effective to determine tannic acid in the range of 7.0 × 10(-9) to 1.0 × 10(-5) mol/L with a determination limit of 2.3 × 10(-9) mol/L. The relative standard deviation is 2.6% for the determination of 5.0 × 10(-6 )mol/L tannic acid (n = 11). The method has been applied to determine the content of tannic acid in industrial wastewater with satisfactory results. It is believed that the CL reaction formed singlet oxygen (1)O(2)* and the emission was from an excited oxygen molecular pair O₂(¹Δ(g))O₂(¹∑⁻(g)) in the KIO₄-H₂O₂-Tween40 reaction. Tween40 played an important role in enhancing stabilization of the excited oxygen molecular pair O₂(¹Δ(g))O₂(¹∑⁻(g)) and in increasing CL intensity.

pubmed23n0857_8130

Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models.

suPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion. The current study was designed to investigate the roles of uPA and suPAR in FSGS in clinical and mouse models. Clinical subjects including those with biopsy-proven FSGS and MCD were enrolled. To verify the role of uPA in FSGS, Adriamycin was used to induce FSGS in uPA knockout (uPA(-/-)) and BALB/c (WT) mice. Proteinuria and suPAR, the cleaved/intact forms of the circulating suPAR, and possible proteases involving cleavage of the suPAR were also studied. FSGS clinical cases presented significantly higher serum levels of suPAR and Cr and lower serum levels of uPA. In the mice model, the uPA(-/-) group exhibited faster disease progression and worsening proteinuria than the WT group. In addition, the uPA(-/-) group had higher plasma suPAR levels, glomerular cell apoptosis, and dysregulation of the Th1/Th2 balance. In an analysis of suPAR variants in FSGS, both the intact and cleaved forms of the suPAR were higher in clinical subjects and the mouse model. However, the process of suPAR cleavage was not mediated by enzymatic activities of the uPA, elastase, or cathepsin G. A deficiency of uPA accelerated the progression of Adriamycin-induced mouse FSGS model. Decrease of serum uPA levels may be an indicator of the progression of FSGS in clinical subjects and animal models.

Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models. suPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion. The current study was designed to investigate the roles of uPA and suPAR in FSGS in clinical and mouse models. Clinical subjects including those with biopsy-proven FSGS and MCD were enrolled. To verify the role of uPA in FSGS, Adriamycin was used to induce FSGS in uPA knockout (uPA(-/-)) and BALB/c (WT) mice. Proteinuria and suPAR, the cleaved/intact forms of the circulating suPAR, and possible proteases involving cleavage of the suPAR were also studied. FSGS clinical cases presented significantly higher serum levels of suPAR and Cr and lower serum levels of uPA. In the mice model, the uPA(-/-) group exhibited faster disease progression and worsening proteinuria than the WT group. In addition, the uPA(-/-) group had higher plasma suPAR levels, glomerular cell apoptosis, and dysregulation of the Th1/Th2 balance. In an analysis of suPAR variants in FSGS, both the intact and cleaved forms of the suPAR were higher in clinical subjects and the mouse model. However, the process of suPAR cleavage was not mediated by enzymatic activities of the uPA, elastase, or cathepsin G. A deficiency of uPA accelerated the progression of Adriamycin-induced mouse FSGS model. Decrease of serum uPA levels may be an indicator of the progression of FSGS in clinical subjects and animal models.

pubmed23n1115_1367

Pan-cancer single-cell landscape of tumor-infiltrating T cells.

T cells play a central role in cancer immunotherapy, but we lack systematic comparison of the heterogeneity and dynamics of tumor-infiltrating T cells across cancer types. We built a single-cell RNA-sequencing pan-cancer atlas of T cells for 316 donors across 21 cancer types and revealed distinct T cell composition patterns. We found multiple state-transition paths in the exhaustion of CD8<sup+</sup T cells and the preference of those paths among different tumor types. Certain T cell populations showed specific correlation with patient properties such as mutation burden, shedding light on the possible determinants of the tumor microenvironment. T cell compositions within tumors alone could classify cancer patients into groups with clinical trait specificity, providing new insights into T cell immunity and precision immunotherapy targeting T cells.

Pan-cancer single-cell landscape of tumor-infiltrating T cells. T cells play a central role in cancer immunotherapy, but we lack systematic comparison of the heterogeneity and dynamics of tumor-infiltrating T cells across cancer types. We built a single-cell RNA-sequencing pan-cancer atlas of T cells for 316 donors across 21 cancer types and revealed distinct T cell composition patterns. We found multiple state-transition paths in the exhaustion of CD8<sup+</sup T cells and the preference of those paths among different tumor types. Certain T cell populations showed specific correlation with patient properties such as mutation burden, shedding light on the possible determinants of the tumor microenvironment. T cell compositions within tumors alone could classify cancer patients into groups with clinical trait specificity, providing new insights into T cell immunity and precision immunotherapy targeting T cells.

pubmed23n0289_3528

Body fluid overload and bioelectrical impedance analysis in renal patients.

Using a new bivariate vectorial approach to the standard bioimpedance analysis (tetrapolar, 50-kHz frequency), we evaluated the performance of a graphical method for the identification of patients with fluid overload. Two hundred and seventeen adult Caucasian subjects were divided into four classification groups: 86 healthy control subjects, 55 patients with mild-to-terminal chronic renal failure in conservative treatment (15% with apparent edema), 36 patients with idiopathic nephrotic proteinuria (58% with apparent edema), and 40 obese subjects. We found a bioimpedance threshold for apparent edema on the lower pole of the sex-specific 75% tolerance ellipse (bivariate tolerance interval) of the healthy population. This innovative graphical method allows identification, monitoring and therapy planning of patients with fluid overload using direct bioimpedance measurements without any assumption on body composition.

Body fluid overload and bioelectrical impedance analysis in renal patients. Using a new bivariate vectorial approach to the standard bioimpedance analysis (tetrapolar, 50-kHz frequency), we evaluated the performance of a graphical method for the identification of patients with fluid overload. Two hundred and seventeen adult Caucasian subjects were divided into four classification groups: 86 healthy control subjects, 55 patients with mild-to-terminal chronic renal failure in conservative treatment (15% with apparent edema), 36 patients with idiopathic nephrotic proteinuria (58% with apparent edema), and 40 obese subjects. We found a bioimpedance threshold for apparent edema on the lower pole of the sex-specific 75% tolerance ellipse (bivariate tolerance interval) of the healthy population. This innovative graphical method allows identification, monitoring and therapy planning of patients with fluid overload using direct bioimpedance measurements without any assumption on body composition.

pubmed23n0971_13154

Oxytocin Manipulation Alters Neural Activity in Response to Social Stimuli in Eusocial Naked Mole-Rats.

The social decision-making network (SDMN) is a conserved neural circuit that modulates a range of social behaviors via context-specific patterns of activation that may be controlled in part by oxytocinergic signaling. We have previously characterized oxytocin's (OT) influence on prosociality in the naked mole-rat, a eusocial mammalian species, and its altered neural distribution between animals of differing social status. Here, we asked two questions: (1) do patterns of activation in the SDMN vary by social context and (2) is functional connectivity of the SDMN altered by OT manipulation? Adult subordinate naked mole-rats were exposed to one of three types of stimuli (three behavioral paradigms: familiar adult conspecific, unfamiliar adult conspecific, or familiar pups) while manipulating OT (three manipulations: saline, OT, or OT antagonist). Immediate early gene c-Fos activity was quantified using immunohistochemistry across SDMN regions. Network analyses indicated that the SDMN is conserved in naked mole-rats and functions in a context-dependent manner. Specific brain regions were recruited with each behavioral paradigm suggesting a role for the nucleus accumbens in social valence and sociosexual interaction, the prefrontal cortex in assessing/establishing social dominance, and the hippocampus in pup recognition. Furthermore, while OT manipulation was generally disruptive to coordinated neural activity, the specific effects were context-dependent supporting the hypothesis that oxytocinergic signaling promotes context appropriate social behaviors by modulating co-ordinated activity of the SDMN.

Oxytocin Manipulation Alters Neural Activity in Response to Social Stimuli in Eusocial Naked Mole-Rats. The social decision-making network (SDMN) is a conserved neural circuit that modulates a range of social behaviors via context-specific patterns of activation that may be controlled in part by oxytocinergic signaling. We have previously characterized oxytocin's (OT) influence on prosociality in the naked mole-rat, a eusocial mammalian species, and its altered neural distribution between animals of differing social status. Here, we asked two questions: (1) do patterns of activation in the SDMN vary by social context and (2) is functional connectivity of the SDMN altered by OT manipulation? Adult subordinate naked mole-rats were exposed to one of three types of stimuli (three behavioral paradigms: familiar adult conspecific, unfamiliar adult conspecific, or familiar pups) while manipulating OT (three manipulations: saline, OT, or OT antagonist). Immediate early gene c-Fos activity was quantified using immunohistochemistry across SDMN regions. Network analyses indicated that the SDMN is conserved in naked mole-rats and functions in a context-dependent manner. Specific brain regions were recruited with each behavioral paradigm suggesting a role for the nucleus accumbens in social valence and sociosexual interaction, the prefrontal cortex in assessing/establishing social dominance, and the hippocampus in pup recognition. Furthermore, while OT manipulation was generally disruptive to coordinated neural activity, the specific effects were context-dependent supporting the hypothesis that oxytocinergic signaling promotes context appropriate social behaviors by modulating co-ordinated activity of the SDMN.

pubmed23n0699_6399

Rathke cleft cysts in pediatric patients: presentation, surgical management, and postoperative outcomes.

Rathke cleft cysts (RCC) are benign sellar lesions most often found in adults, and more infrequently in children. They are generally asymptomatic but sometimes require surgical treatment through a transsphenoidal corridor. The purpose of this study was to compare adult versus pediatric cases of RCC. The authors retrospectively reviewed presenting symptoms, MR imaging findings, laboratory study results, and pathological findings in 147 adult and 14 pediatric patients who underwent surgery for treatment of RCCs at the University of Californial at San Francisco between 1996 and 2008. In both the adult and pediatric groups, most patients were female (78% of adults, 79% of pediatric patients, p = 0.9). Headache was the most common symptom in both groups (reported by 50% of pediatric patients and 33% of adults, p = 0.2). Preoperative hypopituitarism occurred in 41% of adults and 45% of pediatric patients (p = 0.8). Growth delay, a uniquely pediatric finding, was a presenting sign in 29% of pediatric patients. Visual complaints were a presenting symptom in 16% of adult and 7% of pediatric patients (p = 0.4). There was no difference between median cyst size in adults versus pediatric patients (1.2 cm in both, p = 0.7). Temporary or permanent postoperative diabetes insipidus occurred in 12% of adults and 21% of pediatric patients (p = 0.4). Kaplan-Meier analysis revealed an 8% RCC recurrence rate at 2 years for each group (p = 0.5). The incidence of RCCs is much lower in the pediatric population; however, symptoms, imaging findings, and outcomes are similar, suggesting that pediatric RCCs arise from growth of remnants of the embryonic Rathke pouch earlier in life than adult RCCs but do not differ in any other way. It is important to consider RCCs in the differential diagnosis when pediatric patients present with visual impairment, unexplained headache, or hypopituitarism including growth delay. Although the average RCC size was similar in our pediatric and adult patient groups, the smaller size of the pituitary gland in pediatric patients suggests an increased relative RCC size.

Rathke cleft cysts in pediatric patients: presentation, surgical management, and postoperative outcomes. Rathke cleft cysts (RCC) are benign sellar lesions most often found in adults, and more infrequently in children. They are generally asymptomatic but sometimes require surgical treatment through a transsphenoidal corridor. The purpose of this study was to compare adult versus pediatric cases of RCC. The authors retrospectively reviewed presenting symptoms, MR imaging findings, laboratory study results, and pathological findings in 147 adult and 14 pediatric patients who underwent surgery for treatment of RCCs at the University of Californial at San Francisco between 1996 and 2008. In both the adult and pediatric groups, most patients were female (78% of adults, 79% of pediatric patients, p = 0.9). Headache was the most common symptom in both groups (reported by 50% of pediatric patients and 33% of adults, p = 0.2). Preoperative hypopituitarism occurred in 41% of adults and 45% of pediatric patients (p = 0.8). Growth delay, a uniquely pediatric finding, was a presenting sign in 29% of pediatric patients. Visual complaints were a presenting symptom in 16% of adult and 7% of pediatric patients (p = 0.4). There was no difference between median cyst size in adults versus pediatric patients (1.2 cm in both, p = 0.7). Temporary or permanent postoperative diabetes insipidus occurred in 12% of adults and 21% of pediatric patients (p = 0.4). Kaplan-Meier analysis revealed an 8% RCC recurrence rate at 2 years for each group (p = 0.5). The incidence of RCCs is much lower in the pediatric population; however, symptoms, imaging findings, and outcomes are similar, suggesting that pediatric RCCs arise from growth of remnants of the embryonic Rathke pouch earlier in life than adult RCCs but do not differ in any other way. It is important to consider RCCs in the differential diagnosis when pediatric patients present with visual impairment, unexplained headache, or hypopituitarism including growth delay. Although the average RCC size was similar in our pediatric and adult patient groups, the smaller size of the pituitary gland in pediatric patients suggests an increased relative RCC size.

pubmed23n0562_20637

In vivo vasculogenic potential of human blood-derived endothelial progenitor cells.

Vascularization of tissues is a major challenge of tissue engineering (TE). We hypothesize that blood-derived endothelial progenitor cells (EPCs) have the required proliferative and vasculogenic activity to create vascular networks in vivo. To test this, EPCs isolated from human umbilical cord blood or from adult peripheral blood, and human saphenous vein smooth muscle cells (HSVSMCs) as a source of perivascular cells, were combined in Matrigel and implanted subcutaneously into immunodeficient mice. Evaluation of implants at one week revealed an extensive network of human-specific lumenal structures containing erythrocytes, indicating formation of functional anastomoses with the host vasculature. Quantitative analyses showed the microvessel density was significantly superior to that generated by human dermal microvascular endothelial cells (HDMECs) but similar to that generated by human umbilical vein endothelial cells (HUVECs). We also found that as EPCs were expanded in culture, their morphology, growth kinetics, and proliferative responses toward angiogenic factors progressively resembled those of HDMECs, indicating a process of in vitro maturation. This maturation correlated with a decrease in the degree of vascularization in vivo, which could be compensated for by increasing the number of EPCs seeded into the implants. Our findings strongly support the use of human EPCs to form vascular networks in engineered organs and tissues.

In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Vascularization of tissues is a major challenge of tissue engineering (TE). We hypothesize that blood-derived endothelial progenitor cells (EPCs) have the required proliferative and vasculogenic activity to create vascular networks in vivo. To test this, EPCs isolated from human umbilical cord blood or from adult peripheral blood, and human saphenous vein smooth muscle cells (HSVSMCs) as a source of perivascular cells, were combined in Matrigel and implanted subcutaneously into immunodeficient mice. Evaluation of implants at one week revealed an extensive network of human-specific lumenal structures containing erythrocytes, indicating formation of functional anastomoses with the host vasculature. Quantitative analyses showed the microvessel density was significantly superior to that generated by human dermal microvascular endothelial cells (HDMECs) but similar to that generated by human umbilical vein endothelial cells (HUVECs). We also found that as EPCs were expanded in culture, their morphology, growth kinetics, and proliferative responses toward angiogenic factors progressively resembled those of HDMECs, indicating a process of in vitro maturation. This maturation correlated with a decrease in the degree of vascularization in vivo, which could be compensated for by increasing the number of EPCs seeded into the implants. Our findings strongly support the use of human EPCs to form vascular networks in engineered organs and tissues.

pubmed23n0732_7971

Sulfation of fulvestrant by human liver cytosols and recombinant SULT1A1 and SULT1E1.

Fulvestrant (Faslodex™) is a pure antiestrogen that is approved to treat hormone receptor-positive metastatic breast cancer in postmenopausal women. Previous studies have demonstrated that fulvestrant metabolism in humans involves cytochromes P450 and UDP-glucuronosyltransferases (UGTs). To date, fulvestrant sulfation has not been characterized. This study examined fulvestrant sulfation with nine recombinant sulfotransferases and found that only SULT1A1 and SULT1E1 displayed catalytic activity toward this substrate, with K(m) of 4.2 ± 0.99 and 0.2 ± 0.16 μM, respectively. In vitro assays of 104 human liver cytosols revealed marked individual variability that was highly correlated with β-naphthol sulfation (SULT1A1 diagnostic substrate; r = 0.98, P &lt; 0.0001), but not with 17β-estradiol sulfation (SULT1E1 diagnostic substrate; r = 0.16, P = 0.10). Fulvestrant sulfation was correlated with both SULT1A1*1/2 genotype (P value = 0.023) and copy number (P &lt; 0.0001). These studies suggest that factors influencing SULT1A1/1E1 tissue expression and/or enzymatic activity could influence the efficacy of fulvestrant therapy.

Sulfation of fulvestrant by human liver cytosols and recombinant SULT1A1 and SULT1E1. Fulvestrant (Faslodex™) is a pure antiestrogen that is approved to treat hormone receptor-positive metastatic breast cancer in postmenopausal women. Previous studies have demonstrated that fulvestrant metabolism in humans involves cytochromes P450 and UDP-glucuronosyltransferases (UGTs). To date, fulvestrant sulfation has not been characterized. This study examined fulvestrant sulfation with nine recombinant sulfotransferases and found that only SULT1A1 and SULT1E1 displayed catalytic activity toward this substrate, with K(m) of 4.2 ± 0.99 and 0.2 ± 0.16 μM, respectively. In vitro assays of 104 human liver cytosols revealed marked individual variability that was highly correlated with β-naphthol sulfation (SULT1A1 diagnostic substrate; r = 0.98, P &lt; 0.0001), but not with 17β-estradiol sulfation (SULT1E1 diagnostic substrate; r = 0.16, P = 0.10). Fulvestrant sulfation was correlated with both SULT1A1*1/2 genotype (P value = 0.023) and copy number (P &lt; 0.0001). These studies suggest that factors influencing SULT1A1/1E1 tissue expression and/or enzymatic activity could influence the efficacy of fulvestrant therapy.

pubmed23n0237_6971

Platysma musculocutaneous flap: clinical and anatomic considerations in head and neck reconstruction.

The platysma musculocutaneous flap was used in 14 patients for reconstruction of the oral lining and external skin coverage in the head and neck area. Complications occurred in five patients. Only one patient, however, required further surgery and this was for correction of a poor cosmetic result. The skin and subjacent muscle are supplied by a major vascular pedicle from the facial artery and vein and a minor pedicle from the transverse cervical artery and vein. Either pedicle can be used as the pivot for the flap's arc of rotation. The donor defect can be closed primarily and did not present any problems. The flap can be raised with both its motor and sensory supply intact. The thinness and pliability, color match, and proximity make this flap a useful adjunct in head and neck surgery.

Platysma musculocutaneous flap: clinical and anatomic considerations in head and neck reconstruction. The platysma musculocutaneous flap was used in 14 patients for reconstruction of the oral lining and external skin coverage in the head and neck area. Complications occurred in five patients. Only one patient, however, required further surgery and this was for correction of a poor cosmetic result. The skin and subjacent muscle are supplied by a major vascular pedicle from the facial artery and vein and a minor pedicle from the transverse cervical artery and vein. Either pedicle can be used as the pivot for the flap's arc of rotation. The donor defect can be closed primarily and did not present any problems. The flap can be raised with both its motor and sensory supply intact. The thinness and pliability, color match, and proximity make this flap a useful adjunct in head and neck surgery.

pubmed23n0954_26264

An extension of the RiMAX multipath estimation algorithm for ultra-wideband channel modeling.

This work presents an extension of the high-resolution RiMAX multipath estimation algorithm, enabling the analysis of frequency-dependent propagation parameters for ultra-wideband (UWB) channel modeling. Since RiMAX is a narrowband algorithm, it does not account for the frequency-dependency of the radio channel or the environment. As such, the impact of certain materials in which these systems operate can no longer be considered constant with respect to frequency, preventing an accurate estimation of multipath parameters for UWB communication. In order to track both the specular and dense multipath components (SMC and DMC) over frequency, an extension to the RiMAX algorithm was developed that can process UWB measurement data. The advantage of our approach is that geometrical propagation parameters do not appear or disappear from one sub-band onto the next. The UWB-RiMAX algorithm makes it possible to re-evaluate common radio channel parameters for DMC in the wideband scenario, and to extend the well-known deterministic propagation model comprising of SMC alone, towards a more hybrid model containing the stochastic contributions from the DMC's distributed diffuse scattering as well. Our algorithm was tested with synthetic radio channel models in an indoor environment, which show that our algorithm can match up to 99% of the SMC parameters according to the multipath component distance (MCD) metric and that the DMC reverberation time known from the theory of room electromagnetics can be estimated on average with an error margin of less than 2 ns throughout the UWB frequency band. We also present some preliminary results in an indoor environment, which indicate a strong presence of DMC and thus diffuse scattering. The DMC power represents up to 50% of the total measured power for the lower UWB frequencies and reduces to around 30% for the higher UWB frequencies.

An extension of the RiMAX multipath estimation algorithm for ultra-wideband channel modeling. This work presents an extension of the high-resolution RiMAX multipath estimation algorithm, enabling the analysis of frequency-dependent propagation parameters for ultra-wideband (UWB) channel modeling. Since RiMAX is a narrowband algorithm, it does not account for the frequency-dependency of the radio channel or the environment. As such, the impact of certain materials in which these systems operate can no longer be considered constant with respect to frequency, preventing an accurate estimation of multipath parameters for UWB communication. In order to track both the specular and dense multipath components (SMC and DMC) over frequency, an extension to the RiMAX algorithm was developed that can process UWB measurement data. The advantage of our approach is that geometrical propagation parameters do not appear or disappear from one sub-band onto the next. The UWB-RiMAX algorithm makes it possible to re-evaluate common radio channel parameters for DMC in the wideband scenario, and to extend the well-known deterministic propagation model comprising of SMC alone, towards a more hybrid model containing the stochastic contributions from the DMC's distributed diffuse scattering as well. Our algorithm was tested with synthetic radio channel models in an indoor environment, which show that our algorithm can match up to 99% of the SMC parameters according to the multipath component distance (MCD) metric and that the DMC reverberation time known from the theory of room electromagnetics can be estimated on average with an error margin of less than 2 ns throughout the UWB frequency band. We also present some preliminary results in an indoor environment, which indicate a strong presence of DMC and thus diffuse scattering. The DMC power represents up to 50% of the total measured power for the lower UWB frequencies and reduces to around 30% for the higher UWB frequencies.

pubmed23n1002_7254

Vapor-Transport Synthesis and Annealing Study of Zn _<i>x</i> Mg_1-<i>x</i> O Nanowire Arrays for Selective, Solar-Blind UV-C Detection.

This work uniquely reports the synthesis of Zn <sub<ix</i</sub Mg<sub1-<ix</i</sub O nanowires and submicron columns by utilizing a traditional carbothermal reduction process toward forming ZnO nanowire ultraviolet detectors, while simultaneously utilizing Mg<sub3</subN<sub2</sub as the source of Mg. To investigate the relationship between Mg content in the ZnO lattice and the cutoff wavelength for high spectral responsivity, the nanowires were annealed in a series of designed conditions, whereas chemical, nanostructural, and optoelectronic characteristics were compared before and after treatment. Postanneal scanning electron micrographs revealed a reduction of the average ensemble nanowire dimensions, which was correlated to the modification of ZnO lattice parameters stemming from Zn<sup2+</sup dissociation and Mg<sup2+</sup substitution (confirmed via Raman spectroscopy). The analysis of cathodoluminescence spectra revealed a blueshift of the peak alloy band-edge emission along with a redshift of the ZnO band-edge emission; and both were found to be strong functions of the annealing temperature. The conversion of Zn<sub2</subSiO<sub4</sub to Mg<sub2</subSiO<sub4</sub (in O<sub2</sub) and MgSiO<sub3</sub (in Ar) was found to correspond to transformations (shifting and scaling) of high-energy luminescence peaks and was confirmed with X-ray diffraction analysis. The tunability of the cutoff photodetection wavelength was evaluated as the nanowire arrays exhibited selective absorption by retaining elevated conduction under high-energy UV-C irradiation after thermal treatment but exhibiting suppressed conductivity and a single order of magnitude reduction in both spectral responsivity (<iR</i <subλ</sub) and photoconductive gain (<iG</i) under UV-A illumination. Noise analysis revealed that the variation of detectivity (<iD</i*) depended on the regime of ultraviolet irradiation, and that these variations are related to thermal noise resulting from oxygen-related defects on both nanowire and substrate surfaces. These results suggest a minor design tradeoff between the noise characteristics of thermally treated ZnMgO nanowire array UV detectors and the tunability of their spectral sensitivity.

Vapor-Transport Synthesis and Annealing Study of Zn _<i>x</i> Mg_1-<i>x</i> O Nanowire Arrays for Selective, Solar-Blind UV-C Detection. This work uniquely reports the synthesis of Zn <sub<ix</i</sub Mg<sub1-<ix</i</sub O nanowires and submicron columns by utilizing a traditional carbothermal reduction process toward forming ZnO nanowire ultraviolet detectors, while simultaneously utilizing Mg<sub3</subN<sub2</sub as the source of Mg. To investigate the relationship between Mg content in the ZnO lattice and the cutoff wavelength for high spectral responsivity, the nanowires were annealed in a series of designed conditions, whereas chemical, nanostructural, and optoelectronic characteristics were compared before and after treatment. Postanneal scanning electron micrographs revealed a reduction of the average ensemble nanowire dimensions, which was correlated to the modification of ZnO lattice parameters stemming from Zn<sup2+</sup dissociation and Mg<sup2+</sup substitution (confirmed via Raman spectroscopy). The analysis of cathodoluminescence spectra revealed a blueshift of the peak alloy band-edge emission along with a redshift of the ZnO band-edge emission; and both were found to be strong functions of the annealing temperature. The conversion of Zn<sub2</subSiO<sub4</sub to Mg<sub2</subSiO<sub4</sub (in O<sub2</sub) and MgSiO<sub3</sub (in Ar) was found to correspond to transformations (shifting and scaling) of high-energy luminescence peaks and was confirmed with X-ray diffraction analysis. The tunability of the cutoff photodetection wavelength was evaluated as the nanowire arrays exhibited selective absorption by retaining elevated conduction under high-energy UV-C irradiation after thermal treatment but exhibiting suppressed conductivity and a single order of magnitude reduction in both spectral responsivity (<iR</i <subλ</sub) and photoconductive gain (<iG</i) under UV-A illumination. Noise analysis revealed that the variation of detectivity (<iD</i*) depended on the regime of ultraviolet irradiation, and that these variations are related to thermal noise resulting from oxygen-related defects on both nanowire and substrate surfaces. These results suggest a minor design tradeoff between the noise characteristics of thermally treated ZnMgO nanowire array UV detectors and the tunability of their spectral sensitivity.

pubmed23n1005_6114

The effects of serum levels, and alterations in the genes of binding protein and receptor of vitamin D on gastric cancer.

Due to many biological cell functions of vitamin D including regulation of cell survival, proliferation and differentiation, the metabolism of itself gains importance in the development of several types of cancer. This case-control study was designed to evaluate the risk of gastric cancer development in terms of VDR rs2228570 &amp; rs731236, and VDBP rs7041 polymorphisms, and serum levels of vitamin D. The study consists of 77 gastric cancer patients and 84 healthy individuals. VDR and VDBP gene polymorphisms and vitamin D levels were determined by using PCR-RFLP and HPLC methods. The distribution of VDR or VDBP gene variants were not different in study groups. The serum level of 25-hydroxyvitamin D was significantly lower in gastric cancer patients versus controls (16 ± 6 → 11 ± 6 ng/ml) in which male patients have higher levels than females. Although the whole study population lacks normal levels of 25-hydroxyvitamin D, it was found that the risk of the development of gastric cancer was approximately fourfold higher in cases with severe vitamin D (&lt; 10 ng/ml) deficiency. Our results indicate that VDR rs731236 &amp; rs2228570 or VDBP rs7041 polymorphisms were not risk factors for the development of gastric cancer individually, however, lower serum levels of vitamin D may be a contributory risk for both predisposition and development of gastric cancer.

The effects of serum levels, and alterations in the genes of binding protein and receptor of vitamin D on gastric cancer. Due to many biological cell functions of vitamin D including regulation of cell survival, proliferation and differentiation, the metabolism of itself gains importance in the development of several types of cancer. This case-control study was designed to evaluate the risk of gastric cancer development in terms of VDR rs2228570 &amp; rs731236, and VDBP rs7041 polymorphisms, and serum levels of vitamin D. The study consists of 77 gastric cancer patients and 84 healthy individuals. VDR and VDBP gene polymorphisms and vitamin D levels were determined by using PCR-RFLP and HPLC methods. The distribution of VDR or VDBP gene variants were not different in study groups. The serum level of 25-hydroxyvitamin D was significantly lower in gastric cancer patients versus controls (16 ± 6 → 11 ± 6 ng/ml) in which male patients have higher levels than females. Although the whole study population lacks normal levels of 25-hydroxyvitamin D, it was found that the risk of the development of gastric cancer was approximately fourfold higher in cases with severe vitamin D (&lt; 10 ng/ml) deficiency. Our results indicate that VDR rs731236 &amp; rs2228570 or VDBP rs7041 polymorphisms were not risk factors for the development of gastric cancer individually, however, lower serum levels of vitamin D may be a contributory risk for both predisposition and development of gastric cancer.

pubmed23n1160_25238

Different Gene Sets Are Associated With Azacitidine Response In Vitro Versus in Myelodysplastic Syndrome Patients.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders characterized by dysplasia, ineffective hematopoiesis, and predisposition to secondary acute myeloid leukemias (sAML). Azacitidine (AZA) is the standard care for high-risk MDS patients not eligible for allogenic bone marrow transplantation. However, only half of the patients respond to AZA and eventually all patients relapse. Response-predicting biomarkers and combinatorial drugs targets enhancing therapy response and its duration are needed. Here, we have taken a dual approach. First, we have evaluated genes encoding chromatin regulators for their capacity to modulate AZA response. We were able to validate several genes, whose genetic inhibition affected the cellular AZA response, including 4 genes encoding components of Imitation SWItch chromatin remodeling complex pointing toward a specific function and co-vulnerability. Second, we have used a classical cohort analysis approach measuring the expression of a gene panel in bone marrow samples from 36 MDS patients subsequently receiving AZA. The gene panel included the identified AZA modulators, genes known to be involved in AZA metabolism and previously identified candidate modulators. In addition to confirming a number of previously made observations, we were able to identify several new associations, such as <iNSUN3</i that correlated with increased overall survival. Taken together, we have identified a number of genes associated with AZA response in vitro and in patients. These groups of genes are largely nonoverlapping suggesting that different gene sets need to be exploited for the development of combinatorial drug targets and response-predicting biomarkers.

Different Gene Sets Are Associated With Azacitidine Response In Vitro Versus in Myelodysplastic Syndrome Patients. Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders characterized by dysplasia, ineffective hematopoiesis, and predisposition to secondary acute myeloid leukemias (sAML). Azacitidine (AZA) is the standard care for high-risk MDS patients not eligible for allogenic bone marrow transplantation. However, only half of the patients respond to AZA and eventually all patients relapse. Response-predicting biomarkers and combinatorial drugs targets enhancing therapy response and its duration are needed. Here, we have taken a dual approach. First, we have evaluated genes encoding chromatin regulators for their capacity to modulate AZA response. We were able to validate several genes, whose genetic inhibition affected the cellular AZA response, including 4 genes encoding components of Imitation SWItch chromatin remodeling complex pointing toward a specific function and co-vulnerability. Second, we have used a classical cohort analysis approach measuring the expression of a gene panel in bone marrow samples from 36 MDS patients subsequently receiving AZA. The gene panel included the identified AZA modulators, genes known to be involved in AZA metabolism and previously identified candidate modulators. In addition to confirming a number of previously made observations, we were able to identify several new associations, such as <iNSUN3</i that correlated with increased overall survival. Taken together, we have identified a number of genes associated with AZA response in vitro and in patients. These groups of genes are largely nonoverlapping suggesting that different gene sets need to be exploited for the development of combinatorial drug targets and response-predicting biomarkers.

pubmed23n0631_9988

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities.

The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities. We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency. We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%). The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities. The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities. We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency. We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%). The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.

pubmed23n0548_7864

[Current possibilities of using antimyocotic drugs in the treatment of various skin disorders].

Current possibilities of using antimycotic drugs in the treatment of various skin disorders. The purpose of this article is to review the literature data on the therapeutic protocols and the results of using some antimycotics in different skin diseases. In addition to the antimycotic action, particular antifungal drugs such as itraconazole, ketoconazole and terbinafine exhibit anti-inflammatory activity by inhibiting the synthesis of 5-lipooxygenase metabolites. As these metabolites are involved in a number of inflammatory and immunoreactive processes the dual action of the drugs may be suitably exploited in the treatment of some skin diseases which are otherwise difficult to cure. Another rationale for the use of antimycotics in certain skin disorders is their action against Malassezia. It has been recently demonstrated that Malassezia, present as a commensal in the epidermis, may play an important role in inducing certain inflammatory processes by stimulating cytokine production by keratinocytes. The antimycotics proved to be useful in the therapy of the following skin conditions: seborrheic dermatitis, Malassezia folliculitis, perioral dermatitis and papulopustular rosacea, as well as adult atopic dermatitis. The use of antimycotic drugs in amicrobial palmoplantar pustulosis and sebopsoriasis remains controversial. These medications are also an alternative in the treatment of leishmaniosis.

[Current possibilities of using antimyocotic drugs in the treatment of various skin disorders]. Current possibilities of using antimycotic drugs in the treatment of various skin disorders. The purpose of this article is to review the literature data on the therapeutic protocols and the results of using some antimycotics in different skin diseases. In addition to the antimycotic action, particular antifungal drugs such as itraconazole, ketoconazole and terbinafine exhibit anti-inflammatory activity by inhibiting the synthesis of 5-lipooxygenase metabolites. As these metabolites are involved in a number of inflammatory and immunoreactive processes the dual action of the drugs may be suitably exploited in the treatment of some skin diseases which are otherwise difficult to cure. Another rationale for the use of antimycotics in certain skin disorders is their action against Malassezia. It has been recently demonstrated that Malassezia, present as a commensal in the epidermis, may play an important role in inducing certain inflammatory processes by stimulating cytokine production by keratinocytes. The antimycotics proved to be useful in the therapy of the following skin conditions: seborrheic dermatitis, Malassezia folliculitis, perioral dermatitis and papulopustular rosacea, as well as adult atopic dermatitis. The use of antimycotic drugs in amicrobial palmoplantar pustulosis and sebopsoriasis remains controversial. These medications are also an alternative in the treatment of leishmaniosis.

pubmed23n0865_10946

Film offers insights into living with dementia.

Former psychiatric nurse Zarreen Jahanpour will attend a movie premiere this week to watch a film about her experience of dementia.

Film offers insights into living with dementia. Former psychiatric nurse Zarreen Jahanpour will attend a movie premiere this week to watch a film about her experience of dementia.

pubmed23n1076_7343

Differential diagnosis of memory impairment in areas affected by a natural disaster:a case report.

We treated a man with a chief complaint of memory impairment after the Great East Japan Earthquake. Initially, he was diagnosed with dementia. However, after several tests, neither could a definitive diagnosis of dementia be reached, nor was there any apparent evidence for depression, epilepsy, delirium, or internal medicine diseases. During the earthquake, the patient experienced the severe trauma of watching his wife being swept away by a tsunami. Furthermore, he experienced separation from his family. Because of this traumatic experience, we suspected that dissociative disorder was involved in the development of the memory impairment and thus, we switched to treatments focusing on emotional support. Subsequently, the patient's memory impairment gradually improved. The present case demonstrates the importance of considering dissociative disorders when examining a patient with memory impairment in areas affected by disasters.

Differential diagnosis of memory impairment in areas affected by a natural disaster:a case report. We treated a man with a chief complaint of memory impairment after the Great East Japan Earthquake. Initially, he was diagnosed with dementia. However, after several tests, neither could a definitive diagnosis of dementia be reached, nor was there any apparent evidence for depression, epilepsy, delirium, or internal medicine diseases. During the earthquake, the patient experienced the severe trauma of watching his wife being swept away by a tsunami. Furthermore, he experienced separation from his family. Because of this traumatic experience, we suspected that dissociative disorder was involved in the development of the memory impairment and thus, we switched to treatments focusing on emotional support. Subsequently, the patient's memory impairment gradually improved. The present case demonstrates the importance of considering dissociative disorders when examining a patient with memory impairment in areas affected by disasters.

pubmed23n0126_14610

Vernier acuity in the cat: its relation to hyperacuity.

Vernier thresholds were measured behaviourally in five cats using offsets in gratings of two spatial frequencies and in single lines. Thresholds ranged from 2.2 to 6.7', and no threshold differences were found across stimuli. These results are discussed in relationships with published spatial resolution data and are related to the optical and neural characteristics of the cat's visual system. It is concluded that if vernier acuity is a hyperacuity in cats, the improvement in grain is not of the same magnitude as it is in humans.

Vernier acuity in the cat: its relation to hyperacuity. Vernier thresholds were measured behaviourally in five cats using offsets in gratings of two spatial frequencies and in single lines. Thresholds ranged from 2.2 to 6.7', and no threshold differences were found across stimuli. These results are discussed in relationships with published spatial resolution data and are related to the optical and neural characteristics of the cat's visual system. It is concluded that if vernier acuity is a hyperacuity in cats, the improvement in grain is not of the same magnitude as it is in humans.

pubmed23n0636_20577

Dravet syndrome: from electroclinical characteristics to molecular biology.

The onset of Dravet syndrome typically occurs within the first year, with prolonged, generalized, or unilateral clonic seizures triggered by fever. In the early stages, other types of refractory seizures usually present that include myoclonic seizures, atypical absences, and partial seizures. Electroencephalography (EEG) findings are not pathognomonic, and signs of cognitive arrest or deterioration progressively appear. In contrast, in adults, myoclonic seizures, atypical absences, and focal seizures tend to disappear, and short tonic-clonic seizures, often associating a focal component, persist particularly during sleep. The sensitivity to fever persists into adulthood, and although mental deterioration occurs in infancy, usually leaving patients with severe mental impairment, further deterioration does not occur. The identification of genes associated with Dravet syndrome and related syndromes hints at the complexity of the etiology of such epilepsies. Identifying SCN1A mutations has become useful as a means to support an early diagnosis of Dravet syndrome, to benefit counseling, and to avoid use of antiepileptic drugs (AEDs) that may have adverse effects. However, the defining characteristics of seizure type and EEG patterns initially identified by Dravet remain fundamental to diagnosis.

Dravet syndrome: from electroclinical characteristics to molecular biology. The onset of Dravet syndrome typically occurs within the first year, with prolonged, generalized, or unilateral clonic seizures triggered by fever. In the early stages, other types of refractory seizures usually present that include myoclonic seizures, atypical absences, and partial seizures. Electroencephalography (EEG) findings are not pathognomonic, and signs of cognitive arrest or deterioration progressively appear. In contrast, in adults, myoclonic seizures, atypical absences, and focal seizures tend to disappear, and short tonic-clonic seizures, often associating a focal component, persist particularly during sleep. The sensitivity to fever persists into adulthood, and although mental deterioration occurs in infancy, usually leaving patients with severe mental impairment, further deterioration does not occur. The identification of genes associated with Dravet syndrome and related syndromes hints at the complexity of the etiology of such epilepsies. Identifying SCN1A mutations has become useful as a means to support an early diagnosis of Dravet syndrome, to benefit counseling, and to avoid use of antiepileptic drugs (AEDs) that may have adverse effects. However, the defining characteristics of seizure type and EEG patterns initially identified by Dravet remain fundamental to diagnosis.

pubmed23n0668_24061

The relative contributions of fear and disgust reductions to improvements in spider phobia following exposure-based treatment.

The present study examines the relative contributions of changes in state fear and disgust emotions to improvements in spider phobia observed with exposure-based treatment. Sixty-one treatment-seeking spider fearful individuals underwent a one-session exposure in vivo treatment. Growth curve analyses indicated that treatment was associated with significant improvements in state fear and disgust reactions to a live spider and self-reported trait spider phobia symptoms. Mediation analyses demonstrated that changes over time in state fear and disgust each explained unique variance in improvements in phobic symptoms over time. Examination of the effect size of the mediated pathways suggests that changes in fear and changes in disgust are important to reductions in the severity of spider phobia symptoms during exposure-based treatment. The implications of these findings for conceptualizing the role of fear and disgust emotions in the maintenance and treatment of spider phobia are discussed.

The relative contributions of fear and disgust reductions to improvements in spider phobia following exposure-based treatment. The present study examines the relative contributions of changes in state fear and disgust emotions to improvements in spider phobia observed with exposure-based treatment. Sixty-one treatment-seeking spider fearful individuals underwent a one-session exposure in vivo treatment. Growth curve analyses indicated that treatment was associated with significant improvements in state fear and disgust reactions to a live spider and self-reported trait spider phobia symptoms. Mediation analyses demonstrated that changes over time in state fear and disgust each explained unique variance in improvements in phobic symptoms over time. Examination of the effect size of the mediated pathways suggests that changes in fear and changes in disgust are important to reductions in the severity of spider phobia symptoms during exposure-based treatment. The implications of these findings for conceptualizing the role of fear and disgust emotions in the maintenance and treatment of spider phobia are discussed.

pubmed23n1122_17550

Vascular Complications Among Patients Undergoing Trans-femoral Transcatheter Aortic Valve Implantation: Prostar <i>vs</i> ProGlide Parallel Technique.

Reliable femoral artery closure devices are essential for the success of trans-femoral Transcatheter Aortic Valve Implantation (TAVI) procedures. Accordingly, device choice might affect vascular complications and bleeding rates. This was a retrospective analysis, comparing vascular complication rates among patients who underwent trans-femoral TAVI with vascular access closure using either the ProGlide parallel suture or Prostar closure devices. We included 191 patients: 106 were treated with Prostar and 85 with ProGlide. The ProGlide group had higher rate of diabetes, chronic kidney disease, peripheral arterial disease, and significantly smaller femoral arteries that were treated via larger sheaths. Valve Academic Research Consortium (VARC)-2 major complications were similar between the groups. (4.7% for ProGlide vs 3.8% for Prostar, P=1), with similar incidence of closure device failure (2 vs 3, P=1). No differences were found after univariant analysis and propensity-score matching in the incidence of major and minor bleeding nor in the rate of in-hospital mortality between ProGlide and Prostar (4.7 vs 2.8%, P=.7, 1.2 vs 2.8%, P=.63, and 1.2 vs .0%, P=.45, respectively). Parallel suture technique using two ProGlide sutures showed comparable rates of vascular complications to the Prostar closure device in higher risk population of TAVI patients.

Vascular Complications Among Patients Undergoing Trans-femoral Transcatheter Aortic Valve Implantation: Prostar <i>vs</i> ProGlide Parallel Technique. Reliable femoral artery closure devices are essential for the success of trans-femoral Transcatheter Aortic Valve Implantation (TAVI) procedures. Accordingly, device choice might affect vascular complications and bleeding rates. This was a retrospective analysis, comparing vascular complication rates among patients who underwent trans-femoral TAVI with vascular access closure using either the ProGlide parallel suture or Prostar closure devices. We included 191 patients: 106 were treated with Prostar and 85 with ProGlide. The ProGlide group had higher rate of diabetes, chronic kidney disease, peripheral arterial disease, and significantly smaller femoral arteries that were treated via larger sheaths. Valve Academic Research Consortium (VARC)-2 major complications were similar between the groups. (4.7% for ProGlide vs 3.8% for Prostar, P=1), with similar incidence of closure device failure (2 vs 3, P=1). No differences were found after univariant analysis and propensity-score matching in the incidence of major and minor bleeding nor in the rate of in-hospital mortality between ProGlide and Prostar (4.7 vs 2.8%, P=.7, 1.2 vs 2.8%, P=.63, and 1.2 vs .0%, P=.45, respectively). Parallel suture technique using two ProGlide sutures showed comparable rates of vascular complications to the Prostar closure device in higher risk population of TAVI patients.

pubmed23n0863_741

Deglycosylation of Tropheryma whipplei biofilm and discrepancies between diagnostic results during Whipple's disease progression.

Whipple's disease is a systemic infectious disease associated with the bacterium Tropheryma whipplei. Numerous reports have presented puzzling discrepancies between diagnosis methods. We addressed this confusion using fluorescent in situ hybridization and immunofluorescence assays to evaluate 34 duodenal biopsies and 1 lymph node biopsy from Whipple's patients. We showed the presence of bacteria in both CK20(+) epithelial cells and CD68(+) macrophages. Bacteria are found embedded in a biofilm hindering the detection of T. whipplei. Only after treatment of biopsies by glycosidases, co-localization of T. whipplei RNA/DNA with bacterial proteins was restored. Moreover, using 13 bronchoalveolar lavages and 7 duodenal biopsies, we found that hydrolysis of the biofilm weakened the bacteria, facilitated bacterial DNA extraction and improved the sensitivity of qPCR detection by up to 1000x opening new perspectives for diagnostic and scientific approaches.

Deglycosylation of Tropheryma whipplei biofilm and discrepancies between diagnostic results during Whipple's disease progression. Whipple's disease is a systemic infectious disease associated with the bacterium Tropheryma whipplei. Numerous reports have presented puzzling discrepancies between diagnosis methods. We addressed this confusion using fluorescent in situ hybridization and immunofluorescence assays to evaluate 34 duodenal biopsies and 1 lymph node biopsy from Whipple's patients. We showed the presence of bacteria in both CK20(+) epithelial cells and CD68(+) macrophages. Bacteria are found embedded in a biofilm hindering the detection of T. whipplei. Only after treatment of biopsies by glycosidases, co-localization of T. whipplei RNA/DNA with bacterial proteins was restored. Moreover, using 13 bronchoalveolar lavages and 7 duodenal biopsies, we found that hydrolysis of the biofilm weakened the bacteria, facilitated bacterial DNA extraction and improved the sensitivity of qPCR detection by up to 1000x opening new perspectives for diagnostic and scientific approaches.

pubmed23n0581_12846

Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis.

In a cohort study, ovarian cancer (280 cases) showed no significant association with tea or coffee, the multivariable rate ratios being 0.94 (95% confidence interval (CI): 0.89, 1.00) and 1.04 (95% CI: 0.97, 1.12) per cup per day, respectively. A meta-analysis also produced no significant findings overall, though the cohort studies showed a significant inverse association for tea.

Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis. In a cohort study, ovarian cancer (280 cases) showed no significant association with tea or coffee, the multivariable rate ratios being 0.94 (95% confidence interval (CI): 0.89, 1.00) and 1.04 (95% CI: 0.97, 1.12) per cup per day, respectively. A meta-analysis also produced no significant findings overall, though the cohort studies showed a significant inverse association for tea.

pubmed23n0383_16

Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts.

Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that transplantation of VEGF-expressing myoblasts could effectively treat acute myocardial infarction by providing VEGF-induced cardioprotection through vasodilatation in the early phase, followed by angiogenesis effects in salvaging ischemic host myocardium combined with the functional benefits of newly formed, skeletal myoblast-derived muscle in the later phase. Primary rat skeletal myoblasts were transfected with the human VEGF(165) gene using hemagglutinating virus of Japan-liposome with &gt;95% transfection efficiency. Four million of these myoblasts (VEGF group), control-transfected myoblasts (control group), or medium only (medium group) was injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. Myocardial VEGF-expression increased for 2 weeks in the VEGF group, resulting in enhanced angiogenesis without the formation of tumors. Grafted myoblasts had differentiated into multinucleated myotubes within host myocardium. Infarct size (33.3+/-1.4%, 38.1+/-1.4%, and 43.7+/-1.6% for VEGF, control, and medium groups, respectively; P=0.0005) was significantly reduced with VEGF treatment, and cardiac function improved in the VEGF group (maximum dP/dt: 4072.0+/-93.6, 3772.5+/-101.1, and 3482.5+/-90.6 mm Hg/s in the 3 groups, respectively; P=0.0011; minimum dP/dt: -504.2+/-68.5, -2311.3+/-57.0, and -2124.0+/-57.9 mm Hg/s, respectively; P=0.0008). This combined strategy of cell transplantation with gene therapy could be of importance for the treatment of acute myocardial infarction.

Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts. Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that transplantation of VEGF-expressing myoblasts could effectively treat acute myocardial infarction by providing VEGF-induced cardioprotection through vasodilatation in the early phase, followed by angiogenesis effects in salvaging ischemic host myocardium combined with the functional benefits of newly formed, skeletal myoblast-derived muscle in the later phase. Primary rat skeletal myoblasts were transfected with the human VEGF(165) gene using hemagglutinating virus of Japan-liposome with &gt;95% transfection efficiency. Four million of these myoblasts (VEGF group), control-transfected myoblasts (control group), or medium only (medium group) was injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. Myocardial VEGF-expression increased for 2 weeks in the VEGF group, resulting in enhanced angiogenesis without the formation of tumors. Grafted myoblasts had differentiated into multinucleated myotubes within host myocardium. Infarct size (33.3+/-1.4%, 38.1+/-1.4%, and 43.7+/-1.6% for VEGF, control, and medium groups, respectively; P=0.0005) was significantly reduced with VEGF treatment, and cardiac function improved in the VEGF group (maximum dP/dt: 4072.0+/-93.6, 3772.5+/-101.1, and 3482.5+/-90.6 mm Hg/s in the 3 groups, respectively; P=0.0011; minimum dP/dt: -504.2+/-68.5, -2311.3+/-57.0, and -2124.0+/-57.9 mm Hg/s, respectively; P=0.0008). This combined strategy of cell transplantation with gene therapy could be of importance for the treatment of acute myocardial infarction.

pubmed23n0298_13336

[Non-Hodgkin gastric lymphoma in a 14-year-old boy].

Lymphomas of the gastrointestinal tract in children are localized most often in the ileocoecal region. We described a rare case of gastric lymphoma in 14-year-old boy.

[Non-Hodgkin gastric lymphoma in a 14-year-old boy]. Lymphomas of the gastrointestinal tract in children are localized most often in the ileocoecal region. We described a rare case of gastric lymphoma in 14-year-old boy.

pubmed23n0228_8320

Presynaptic inhibition, EPSP amplitude, and motor-unit type in triceps surae motoneurons in the cat.

1. Composite group Ia excitatory postsynaptic potentials (EPSPs) produced by heteronymous nerve stimulation were recorded from triceps surae motoneurons of barbiturate-anesthetized cats. Motoneuron rheobase, input resistance, and axonal conduction velocity were measured, and motor units were classified on the basis of the mechanical responses of their muscle units. 2. The amplitude of EPSPs recorded from 33 medial gastrocnemius (MG) motoneurons ranged from 0.6 to 4.3 mV. The mean EPSP amplitude differed among the major MG motor-unit types, increasing in the order fast twitch, fast fatiguing (FF); fast twitch, fatigue resistant (FR); slow twitch, fatigue resistant (S) (FF less than FR less than S). The amplitude of EPSPs recorded from 15 soleus motoneurons ranged from 0.3 to 3.4 mV, with a mean of 1.4 mV. 3. Presynaptic inhibition of EPSPs was produced by trains of conditioning volleys in the posterior biceps-semitendinosus (PBST) nerve. In 33 MG cells PBST conditioning stimulation reduced the amplitude of EPSPs by 11-50%, with a mean inhibition of 27%. The amplitude of EPSPs in 15 soleus motoneurons was decreased by 5-84%, with a mean inhibition of 37%. 4. When the magnitude of presynaptic inhibition was expressed as percent inhibition, there was no relation between presynaptic inhibition and either motor-unit type or the amplitude of the EPSP. However, when presynaptic inhibition was expressed as the absolute amount of inhibition in millivolts, the magnitude of inhibition was highly correlated with EPSP amplitude both across the entire triceps surae population (MG, lateral gastrocnemius, soleus) as well as within each muscle population. This correlation was also significant within the MG FF and FR motor-unit populations. 5. We conclude that EPSP amplitude and not motor-unit type is the major determinant of the magnitude of presynaptic inhibition. However, because of the effect of motor-unit type on EPSP amplitude, the net effect is that presynaptic inhibition increases in the order FF less than FR less than S.

Presynaptic inhibition, EPSP amplitude, and motor-unit type in triceps surae motoneurons in the cat. 1. Composite group Ia excitatory postsynaptic potentials (EPSPs) produced by heteronymous nerve stimulation were recorded from triceps surae motoneurons of barbiturate-anesthetized cats. Motoneuron rheobase, input resistance, and axonal conduction velocity were measured, and motor units were classified on the basis of the mechanical responses of their muscle units. 2. The amplitude of EPSPs recorded from 33 medial gastrocnemius (MG) motoneurons ranged from 0.6 to 4.3 mV. The mean EPSP amplitude differed among the major MG motor-unit types, increasing in the order fast twitch, fast fatiguing (FF); fast twitch, fatigue resistant (FR); slow twitch, fatigue resistant (S) (FF less than FR less than S). The amplitude of EPSPs recorded from 15 soleus motoneurons ranged from 0.3 to 3.4 mV, with a mean of 1.4 mV. 3. Presynaptic inhibition of EPSPs was produced by trains of conditioning volleys in the posterior biceps-semitendinosus (PBST) nerve. In 33 MG cells PBST conditioning stimulation reduced the amplitude of EPSPs by 11-50%, with a mean inhibition of 27%. The amplitude of EPSPs in 15 soleus motoneurons was decreased by 5-84%, with a mean inhibition of 37%. 4. When the magnitude of presynaptic inhibition was expressed as percent inhibition, there was no relation between presynaptic inhibition and either motor-unit type or the amplitude of the EPSP. However, when presynaptic inhibition was expressed as the absolute amount of inhibition in millivolts, the magnitude of inhibition was highly correlated with EPSP amplitude both across the entire triceps surae population (MG, lateral gastrocnemius, soleus) as well as within each muscle population. This correlation was also significant within the MG FF and FR motor-unit populations. 5. We conclude that EPSP amplitude and not motor-unit type is the major determinant of the magnitude of presynaptic inhibition. However, because of the effect of motor-unit type on EPSP amplitude, the net effect is that presynaptic inhibition increases in the order FF less than FR less than S.

pubmed23n0022_4849

Morphologic evidence for retrovirus production by epithelial cells derived from a human testicular tumor metastasis.

Ultrastructural examination of primary and subcultured epithelial cells established in vitro from an abdominal metastasis of a human testicular tumor revealed particles with the morphology of retroviruses. These structures, found only after extensive scanning of the cells, were observed budding from microvilli and from the outer cell membrane and as extracellular particles. Production of these virus particles was stimulated by the incubation of cells in culture medium containing 5-iodo-2'-deoxyuridine and dexamethasone.

Morphologic evidence for retrovirus production by epithelial cells derived from a human testicular tumor metastasis. Ultrastructural examination of primary and subcultured epithelial cells established in vitro from an abdominal metastasis of a human testicular tumor revealed particles with the morphology of retroviruses. These structures, found only after extensive scanning of the cells, were observed budding from microvilli and from the outer cell membrane and as extracellular particles. Production of these virus particles was stimulated by the incubation of cells in culture medium containing 5-iodo-2'-deoxyuridine and dexamethasone.

pubmed23n1090_16050

One-Year Outcomes in a Large Series of Patients Following Implantation of an Extended Depth of Focus Intraocular Lens.

To evaluate clinical outcomes 1 year after implantation of an extended depth of focus intraocular lens (IOL) in a large series of patients. Outcomes of patients who underwent refractive lens exchange or cataract surgery with the implantation of the AT LARA 829MP IOL (Carl Zeiss Meditec AG) were retrospectively reviewed. The near (40 cm), intermediate (66 cm), and distance visual acuity, refractive outcomes, and cumulative rate of adverse events and secondary procedures were evaluated at 12 months postoperatively. A total of 1,894 eyes of 977 patients were implanted with the AT LARA 829MP IOL, with 62.1% of eyes available for the 12-month visit. The overall secondary procedure rate for the whole cohort was: Nd:YAG = 7.8%, laser vision correction = 7.5%, and IOL explantation = 0.63%. The reasons for IOL exchange were intraoperative complications (3 eyes/0.16%) and quality of vision issues (9 eyes/0.48%). Of all eyes available for the 12-month visit that did not undergo laser vision correction or an IOL exchange, 72.0% had monocular uncorrected distance visual acuity of 20/20 or better and the percentage of eyes with monocular uncorrected intermediate and near visual acuity of 20/50 or better was 96.2% and 81.0%, respectively. At 12 months postoperatively, 87.6% of eyes were within ±0.50 diopters of emmetropia. No change in refraction occurred between the 6- and 12-month postoperative visits. The AT LARA 829MP extended depth of focus IOL is able to provide functional distance, intermediate, and near visual acuity. Complications related to the platform of the IOL were uncommon. <b[<iJ Refract Surg</i. 2021;37(6):380-388.]</b.

One-Year Outcomes in a Large Series of Patients Following Implantation of an Extended Depth of Focus Intraocular Lens. To evaluate clinical outcomes 1 year after implantation of an extended depth of focus intraocular lens (IOL) in a large series of patients. Outcomes of patients who underwent refractive lens exchange or cataract surgery with the implantation of the AT LARA 829MP IOL (Carl Zeiss Meditec AG) were retrospectively reviewed. The near (40 cm), intermediate (66 cm), and distance visual acuity, refractive outcomes, and cumulative rate of adverse events and secondary procedures were evaluated at 12 months postoperatively. A total of 1,894 eyes of 977 patients were implanted with the AT LARA 829MP IOL, with 62.1% of eyes available for the 12-month visit. The overall secondary procedure rate for the whole cohort was: Nd:YAG = 7.8%, laser vision correction = 7.5%, and IOL explantation = 0.63%. The reasons for IOL exchange were intraoperative complications (3 eyes/0.16%) and quality of vision issues (9 eyes/0.48%). Of all eyes available for the 12-month visit that did not undergo laser vision correction or an IOL exchange, 72.0% had monocular uncorrected distance visual acuity of 20/20 or better and the percentage of eyes with monocular uncorrected intermediate and near visual acuity of 20/50 or better was 96.2% and 81.0%, respectively. At 12 months postoperatively, 87.6% of eyes were within ±0.50 diopters of emmetropia. No change in refraction occurred between the 6- and 12-month postoperative visits. The AT LARA 829MP extended depth of focus IOL is able to provide functional distance, intermediate, and near visual acuity. Complications related to the platform of the IOL were uncommon. <b[<iJ Refract Surg</i. 2021;37(6):380-388.]</b.

pubmed23n1162_19175

A Comparative Study of Mesoporous Silica and Mesoporous Bioactive Glass Nanoparticles as Non-Viral MicroRNA Vectors for Osteogenesis.

Micro-ribonucleic acid (miRNA)-based therapies show advantages for bone regeneration but need efficient intracellular delivery methods. Inorganic nanoparticles such as mesoporous bioactive glass nanoparticles (MBGN) and mesoporous silica nanoparticles (MSN) have received growing interest in the intracellular delivery of nucleic acids. This study explores the capacity of MBGN and MSN for delivering miRNA to bone marrow mesenchymal stem cells (BMSC) for bone regenerative purposes, with a focus on comparing the two in terms of cell viability, transfection efficiency, and osteogenic actions. Spherical MBGN and MSN with a particle size of ~200 nm and small-sized mesopores were prepared using the sol-gel method, and then the surface was modified with polyethyleneimine for miRNA loading and delivery. The results showed miRNA can be loaded into both nanoparticles within 2 h and was released sustainedly for up to 3 days. Confocal laser scanning microscopy and flow cytometry analysis indicated a high transfection efficiency (&amp;gt;64%) of both nanoparticles without statistical difference. Compared with MSN, MBGN showed stronger activation of alkaline phosphatase and activation of osteocalcin genes. This translated to a greater osteogenic effect of MBGN on BMSC, with Alizarin red staining showing greater mineralization compared with the MSN group. These findings show the potential for MBGN to be used in bone tissue engineering.

A Comparative Study of Mesoporous Silica and Mesoporous Bioactive Glass Nanoparticles as Non-Viral MicroRNA Vectors for Osteogenesis. Micro-ribonucleic acid (miRNA)-based therapies show advantages for bone regeneration but need efficient intracellular delivery methods. Inorganic nanoparticles such as mesoporous bioactive glass nanoparticles (MBGN) and mesoporous silica nanoparticles (MSN) have received growing interest in the intracellular delivery of nucleic acids. This study explores the capacity of MBGN and MSN for delivering miRNA to bone marrow mesenchymal stem cells (BMSC) for bone regenerative purposes, with a focus on comparing the two in terms of cell viability, transfection efficiency, and osteogenic actions. Spherical MBGN and MSN with a particle size of ~200 nm and small-sized mesopores were prepared using the sol-gel method, and then the surface was modified with polyethyleneimine for miRNA loading and delivery. The results showed miRNA can be loaded into both nanoparticles within 2 h and was released sustainedly for up to 3 days. Confocal laser scanning microscopy and flow cytometry analysis indicated a high transfection efficiency (&amp;gt;64%) of both nanoparticles without statistical difference. Compared with MSN, MBGN showed stronger activation of alkaline phosphatase and activation of osteocalcin genes. This translated to a greater osteogenic effect of MBGN on BMSC, with Alizarin red staining showing greater mineralization compared with the MSN group. These findings show the potential for MBGN to be used in bone tissue engineering.

pubmed23n1160_2754

Squared Energy-Resolved Mass Spectrometry Advances Quantitative Bile Acid Submetabolome Characterization.

The bile acid (BA) submetabolome can partially reflect either physiological or pathological status of vertebrates. The structural diversity, however, extensively hinders BA submetabolome clarification. Here, efforts were primarily devoted to enhance structural annotation confidences of BAs, in particular the conjugated BAs, through fortifying a new technology, namely, squared energy-resolved mass spectrometry (ER<sup2</sup-MS), to traditional liquid chromatography with tandem mass spectrometry (LC-MS/MS). Because of possessing two tandem-in-space collision cells, namely, q2 and linear ion trap (LIT) chambers, Qtrap-MS was employed as the fit-for-purpose tool to conduct ER<sup2</sup-MS measurements. The first ER-MS was undertaken in a q2 cell to gain first-generation breakdown graphs to disclose conjugation sites <ivia</i applying the multiple-reaction monitoring (MRM) program, and the second ER-MS was accomplished in a LIT chamber through programming MRM cubed to acquire second-generation breakdown graphs of concerned ions for scaffold characterization. An authentic BA library consisting of commercial BAs together with their <iin vitro</i metabolites was built to record a reference breakdown graph set. Moreover, the so-called universal metabolome standard sample that was prepared by pooling diverse BA-enriched matrices was applied for structural deciphering potential evaluation and quasi-quantitative analysis of all detected BAs as well, according to applying a well-defined quasi-content concept. High-confidence structural analysis was achieved for as many as 201 BAs, and significant impacts occurred for the BA submetabolome of HepG2 cells after lithocholic acid treatment. Together, ER<sup2</sup-MS provides a promising tool to promote, although not limited to, LC-MS/MS-based BA-targeted metabolomics.

Squared Energy-Resolved Mass Spectrometry Advances Quantitative Bile Acid Submetabolome Characterization. The bile acid (BA) submetabolome can partially reflect either physiological or pathological status of vertebrates. The structural diversity, however, extensively hinders BA submetabolome clarification. Here, efforts were primarily devoted to enhance structural annotation confidences of BAs, in particular the conjugated BAs, through fortifying a new technology, namely, squared energy-resolved mass spectrometry (ER<sup2</sup-MS), to traditional liquid chromatography with tandem mass spectrometry (LC-MS/MS). Because of possessing two tandem-in-space collision cells, namely, q2 and linear ion trap (LIT) chambers, Qtrap-MS was employed as the fit-for-purpose tool to conduct ER<sup2</sup-MS measurements. The first ER-MS was undertaken in a q2 cell to gain first-generation breakdown graphs to disclose conjugation sites <ivia</i applying the multiple-reaction monitoring (MRM) program, and the second ER-MS was accomplished in a LIT chamber through programming MRM cubed to acquire second-generation breakdown graphs of concerned ions for scaffold characterization. An authentic BA library consisting of commercial BAs together with their <iin vitro</i metabolites was built to record a reference breakdown graph set. Moreover, the so-called universal metabolome standard sample that was prepared by pooling diverse BA-enriched matrices was applied for structural deciphering potential evaluation and quasi-quantitative analysis of all detected BAs as well, according to applying a well-defined quasi-content concept. High-confidence structural analysis was achieved for as many as 201 BAs, and significant impacts occurred for the BA submetabolome of HepG2 cells after lithocholic acid treatment. Together, ER<sup2</sup-MS provides a promising tool to promote, although not limited to, LC-MS/MS-based BA-targeted metabolomics.

pubmed23n0991_9619

<i>MYD88</i> mutations identify a molecular subgroup of diffuse large B-cell lymphoma with an unfavorable prognosis.

The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of <iMYC/BCL2/BCL6</i as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in <iMYD88/CD79B</i We investigated whether <iMYD88/CD79B</i mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, <iMYD88/CD79B</i mutations were identified by allele-specific polymerase chain reaction or next-generation-sequencing, <iMYC/BCL2/BCL6</i rearrangements were analyzed by fluorescence <iin situ</i hybridization, and EBV was studied by EBV-encoded RNA <iin situ</i hybridization. Associations of molecular features with clinicopathologic characteristics, outcome, and prognosis according to the International Prognostic Index (IPI) were investigated. <iMYD88</i and <iCD79B</i mutations were identified in 29.6% and 12.3%, <iMYC, BCL2</i, and <iBCL6</i rearrangements in 10.6%, 13.6%, and 20.3%, and EBV in 11.7% of DLBCL, respectively. Prominent mutual exclusivity between EBV positivity, rearrangements, and <iMYD88/CD79B</i mutations established the value of molecular markers for the recognition of biologically distinct DLBCL subtypes. <iMYD88</i-mutated DLBCL had a significantly inferior 5-year overall survival than wild-type <iMYD88</i DLBCL (log-rank; <iP</i=0.019). DLBCL without any of the studied aberrations had superior overall survival compared to cases carrying ≥1 aberrancy (log-rank; <iP</i=0.010). <iMYD88</i mutations retained their adverse prognostic impact upon adjustment for other genetic and clinical variables by multivariable analysis and improved the prognostic performance of the IPI. This study demonstrates the clinical utility of defining <iMYD88</i-mutated DLBCL as a distinct molecular subtype with adverse prognosis. Our data call for sequence analysis of <iMYD88</i in routine diagnostics of DLBCL to optimize classification and prognostication, and to guide the development of improved treatment strategies.

<i>MYD88</i> mutations identify a molecular subgroup of diffuse large B-cell lymphoma with an unfavorable prognosis. The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of <iMYC/BCL2/BCL6</i as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in <iMYD88/CD79B</i We investigated whether <iMYD88/CD79B</i mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, <iMYD88/CD79B</i mutations were identified by allele-specific polymerase chain reaction or next-generation-sequencing, <iMYC/BCL2/BCL6</i rearrangements were analyzed by fluorescence <iin situ</i hybridization, and EBV was studied by EBV-encoded RNA <iin situ</i hybridization. Associations of molecular features with clinicopathologic characteristics, outcome, and prognosis according to the International Prognostic Index (IPI) were investigated. <iMYD88</i and <iCD79B</i mutations were identified in 29.6% and 12.3%, <iMYC, BCL2</i, and <iBCL6</i rearrangements in 10.6%, 13.6%, and 20.3%, and EBV in 11.7% of DLBCL, respectively. Prominent mutual exclusivity between EBV positivity, rearrangements, and <iMYD88/CD79B</i mutations established the value of molecular markers for the recognition of biologically distinct DLBCL subtypes. <iMYD88</i-mutated DLBCL had a significantly inferior 5-year overall survival than wild-type <iMYD88</i DLBCL (log-rank; <iP</i=0.019). DLBCL without any of the studied aberrations had superior overall survival compared to cases carrying ≥1 aberrancy (log-rank; <iP</i=0.010). <iMYD88</i mutations retained their adverse prognostic impact upon adjustment for other genetic and clinical variables by multivariable analysis and improved the prognostic performance of the IPI. This study demonstrates the clinical utility of defining <iMYD88</i-mutated DLBCL as a distinct molecular subtype with adverse prognosis. Our data call for sequence analysis of <iMYD88</i in routine diagnostics of DLBCL to optimize classification and prognostication, and to guide the development of improved treatment strategies.

pubmed23n0851_5536

Metabolism pathways in chronic lymphocytic leukemia.

Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

Metabolism pathways in chronic lymphocytic leukemia. Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

pubmed23n0865_7339

Dispersion of Nanocrystalline Fe3O4 within Composite Electrodes: Insights on Battery-Related Electrochemistry.

Aggregation of nanosized materials in composite lithium-ion-battery electrodes can be a significant factor influencing electrochemical behavior. In this study, aggregation was controlled in magnetite, Fe3O4, composite electrodes via oleic acid capping and subsequent dispersion in a carbon black matrix. A heat treatment process was effective in the removal of the oleic acid capping agent while preserving a high degree of Fe3O4 dispersion. Electrochemical testing showed that Fe3O4 dispersion is initially beneficial in delivering a higher functional capacity, in agreement with continuum model simulations. However, increased capacity fade upon extended cycling was observed for the dispersed Fe3O4 composites relative to the aggregated Fe3O4 composites. X-ray absorption spectroscopy measurements of electrodes post cycling indicated that the dispersed Fe3O4 electrodes are more oxidized in the discharged state, consistent with reduced reversibility compared with the aggregated sample. Higher charge-transfer resistance for the dispersed sample after cycling suggests increased surface-film formation on the dispersed, high-surface-area nanocrystalline Fe3O4 compared to the aggregated materials. This study provides insight into the specific effects of aggregation on electrochemistry through a multiscale view of mechanisms for magnetite composite electrodes.

Dispersion of Nanocrystalline Fe3O4 within Composite Electrodes: Insights on Battery-Related Electrochemistry. Aggregation of nanosized materials in composite lithium-ion-battery electrodes can be a significant factor influencing electrochemical behavior. In this study, aggregation was controlled in magnetite, Fe3O4, composite electrodes via oleic acid capping and subsequent dispersion in a carbon black matrix. A heat treatment process was effective in the removal of the oleic acid capping agent while preserving a high degree of Fe3O4 dispersion. Electrochemical testing showed that Fe3O4 dispersion is initially beneficial in delivering a higher functional capacity, in agreement with continuum model simulations. However, increased capacity fade upon extended cycling was observed for the dispersed Fe3O4 composites relative to the aggregated Fe3O4 composites. X-ray absorption spectroscopy measurements of electrodes post cycling indicated that the dispersed Fe3O4 electrodes are more oxidized in the discharged state, consistent with reduced reversibility compared with the aggregated sample. Higher charge-transfer resistance for the dispersed sample after cycling suggests increased surface-film formation on the dispersed, high-surface-area nanocrystalline Fe3O4 compared to the aggregated materials. This study provides insight into the specific effects of aggregation on electrochemistry through a multiscale view of mechanisms for magnetite composite electrodes.

pubmed23n0952_20045

[Fanconi anemia at the University Hospital (CHU) Hassan II of Fez: about 6 cases].

Fanconi anemia is a recessive disorder associated with chromosomal instability. It is marked by phenotypical heterogeneity which includes medullary deficiency, a variable malformation syndrome, a predisposition to develop acute leukaemias myéloïdes (ALM) and a cellular over-sensitiveness with the agents bridging the ADN. The diagnosis is based on the abnormal increase in the rate of spontaneous breaks chromosomal but especially and in a specific way, on a clear increase in these chromosomal breaks in the presence of bifunctional alkylating agents, which is the case in our six patients. Genetic counseling is that available for autosomal recessive diseases. We report our initial observations conducted at the University Hospital (CHU) Hassan II of Fez confirmed by the detection of a large chromosomal instability after culture with Mitomycin C compared to a normal control group. The purpose of this study was to update our knowledge of Fanconi anemia genes and to highlight the role of cytogenetics in its diagnosis and the genetic counseling for better management of affected children and their families.

[Fanconi anemia at the University Hospital (CHU) Hassan II of Fez: about 6 cases]. Fanconi anemia is a recessive disorder associated with chromosomal instability. It is marked by phenotypical heterogeneity which includes medullary deficiency, a variable malformation syndrome, a predisposition to develop acute leukaemias myéloïdes (ALM) and a cellular over-sensitiveness with the agents bridging the ADN. The diagnosis is based on the abnormal increase in the rate of spontaneous breaks chromosomal but especially and in a specific way, on a clear increase in these chromosomal breaks in the presence of bifunctional alkylating agents, which is the case in our six patients. Genetic counseling is that available for autosomal recessive diseases. We report our initial observations conducted at the University Hospital (CHU) Hassan II of Fez confirmed by the detection of a large chromosomal instability after culture with Mitomycin C compared to a normal control group. The purpose of this study was to update our knowledge of Fanconi anemia genes and to highlight the role of cytogenetics in its diagnosis and the genetic counseling for better management of affected children and their families.

pubmed23n0210_11527

Two site-specific endonucleases BinSI and BinSII from Bifidobacterium infantis.

Two site-specific endonucleases, BinSI and BinSII, were isolated from Bifidobacterium infantis S76e. BinSI was found to be an isoschizomer of EcoRII, while BinSII was shown to have the same sequence and cutting specificity as BbeI, 5'-GGCGC decreases C-3'. Both BinSII- and BbeI-generated DNA fragments could be ligated with HaeII-generated DNA fragments.

Two site-specific endonucleases BinSI and BinSII from Bifidobacterium infantis. Two site-specific endonucleases, BinSI and BinSII, were isolated from Bifidobacterium infantis S76e. BinSI was found to be an isoschizomer of EcoRII, while BinSII was shown to have the same sequence and cutting specificity as BbeI, 5'-GGCGC decreases C-3'. Both BinSII- and BbeI-generated DNA fragments could be ligated with HaeII-generated DNA fragments.

pubmed23n0647_1428

Effect of equine chorionic gonadotropin on the efficiency of superovulation induction for in vivo and in vitro embryo production in the cat.

The effects of various dosages of equine chorionic gonadotropin (eCG) on superovulation induction for in vivo and in vitro embryo production were examined in stray cats (Felis catus). Cats (n=286) were allocated into five treatment groups with 0, 50, 100, 200, or 400 IU eCG, followed by 100 IU human chorionic gonadotropin (hCG). In vivo- and in vitro-produced blastocysts were obtained by artificial insemination (AI) and in vitro fertilization (IVF), somatic cell nucleus transfer (SCNT), or parthenogenetic activation (PA). The percentage of cats that developed mature follicles, the percentage of cats with collected embryos, and the mean number of in vivo blastocysts per cat were higher in the 200 IU treatment group (43.9%, 31.8%, and 1.53, respectively) compared with those of the other groups (P&lt;0.05). The percentage of follicular developed cats, the percentage of cumulus-expanded oocytes, and the mean number of collected cumulus-oocyte complexes per cat in the 200 IU (56.7%, 67.8%, and 26.2, respectively) and 400 IU (53.3%, 64.2%, and 26.7, respectively) groups were higher than those in the other groups (P&lt;0.05). Furthermore, the percentage of in vitro-produced blastocyst per cleaved embryos and the average cell number of the blastocysts from IVF (52.7% and 125.8, respectively) was higher than those of the blastocysts from PA (30.1% and 85.2) and higher than those of the blastocysts from SCNT (15.3% and 37.5; P&lt;0.05). In conclusion, the current study demonstrated that in vivo and in vitro embryo production were affected by the dosage of eCG; the best results were obtained with 200 IU.

Effect of equine chorionic gonadotropin on the efficiency of superovulation induction for in vivo and in vitro embryo production in the cat. The effects of various dosages of equine chorionic gonadotropin (eCG) on superovulation induction for in vivo and in vitro embryo production were examined in stray cats (Felis catus). Cats (n=286) were allocated into five treatment groups with 0, 50, 100, 200, or 400 IU eCG, followed by 100 IU human chorionic gonadotropin (hCG). In vivo- and in vitro-produced blastocysts were obtained by artificial insemination (AI) and in vitro fertilization (IVF), somatic cell nucleus transfer (SCNT), or parthenogenetic activation (PA). The percentage of cats that developed mature follicles, the percentage of cats with collected embryos, and the mean number of in vivo blastocysts per cat were higher in the 200 IU treatment group (43.9%, 31.8%, and 1.53, respectively) compared with those of the other groups (P&lt;0.05). The percentage of follicular developed cats, the percentage of cumulus-expanded oocytes, and the mean number of collected cumulus-oocyte complexes per cat in the 200 IU (56.7%, 67.8%, and 26.2, respectively) and 400 IU (53.3%, 64.2%, and 26.7, respectively) groups were higher than those in the other groups (P&lt;0.05). Furthermore, the percentage of in vitro-produced blastocyst per cleaved embryos and the average cell number of the blastocysts from IVF (52.7% and 125.8, respectively) was higher than those of the blastocysts from PA (30.1% and 85.2) and higher than those of the blastocysts from SCNT (15.3% and 37.5; P&lt;0.05). In conclusion, the current study demonstrated that in vivo and in vitro embryo production were affected by the dosage of eCG; the best results were obtained with 200 IU.

pubmed23n1025_20332

Uncovering lead formate crystallization in oil-based paintings.

Lead carboxylates are an extensive group of compounds studied for their promising industrial applications and for their risky behavior when they are formed in oil paintings as corrosion products of lead-based pigments, leading to serious deterioration of paintings. Although the processes leading to the formation of aggregates, protrusions or inclusions, affecting undesirably the appearance of paintings, are assumed to be long term, neo-formed lead carboxylates are detectable in the early stage of paint drying. To uncover the chemical changes in lead pigments during the drying of oil paint films, model systems consisting of minium (Pb3O4) and four common drying oils were studied by X-ray powder diffraction (XRPD), 13C and 207Pb solid state NMR (ssNMR) spectroscopy and Fourier-transformed infrared spectroscopy (FTIR). For the first time, a degradation mechanism of Pb3O4via the crystallization of lead formate (Pb(HCOO)2), at the end of oxidative polymerization of oil paint films, was uncovered. The formation of formic acid in oils was proved by gas chromatography-mass spectrometry (GC-MS). Vapor experiments evidenced the susceptibility of Pb3O4 to react with volatile formic acid released during the autoxidation of oils comparably to the direct pigment-binder interactions in paint films. The investigation of the local environment of lead atoms in the paint film by 207Pb WURST-CPMG NMR spectroscopy showed that Pb(ii) atoms reacted with linseed oil preferentially to form highly crystalline Pb(HCOO)2, while the local chemical environment of Pb(iv) atoms did not change. The results proved the co-existence of (i) highly crystalline Pb(HCOO)2, (ii) a highly mobile amorphous phase corresponding to free carboxylic acids or a nascent lead soap phase and (iii) the remaining Pb3O4 in the polymeric/ionomeric network. Pb(HCOO)2 is assumed to be an intermediate for the conversion of Pb3O4 to lead soaps and/or lead carbonates.

Uncovering lead formate crystallization in oil-based paintings. Lead carboxylates are an extensive group of compounds studied for their promising industrial applications and for their risky behavior when they are formed in oil paintings as corrosion products of lead-based pigments, leading to serious deterioration of paintings. Although the processes leading to the formation of aggregates, protrusions or inclusions, affecting undesirably the appearance of paintings, are assumed to be long term, neo-formed lead carboxylates are detectable in the early stage of paint drying. To uncover the chemical changes in lead pigments during the drying of oil paint films, model systems consisting of minium (Pb3O4) and four common drying oils were studied by X-ray powder diffraction (XRPD), 13C and 207Pb solid state NMR (ssNMR) spectroscopy and Fourier-transformed infrared spectroscopy (FTIR). For the first time, a degradation mechanism of Pb3O4via the crystallization of lead formate (Pb(HCOO)2), at the end of oxidative polymerization of oil paint films, was uncovered. The formation of formic acid in oils was proved by gas chromatography-mass spectrometry (GC-MS). Vapor experiments evidenced the susceptibility of Pb3O4 to react with volatile formic acid released during the autoxidation of oils comparably to the direct pigment-binder interactions in paint films. The investigation of the local environment of lead atoms in the paint film by 207Pb WURST-CPMG NMR spectroscopy showed that Pb(ii) atoms reacted with linseed oil preferentially to form highly crystalline Pb(HCOO)2, while the local chemical environment of Pb(iv) atoms did not change. The results proved the co-existence of (i) highly crystalline Pb(HCOO)2, (ii) a highly mobile amorphous phase corresponding to free carboxylic acids or a nascent lead soap phase and (iii) the remaining Pb3O4 in the polymeric/ionomeric network. Pb(HCOO)2 is assumed to be an intermediate for the conversion of Pb3O4 to lead soaps and/or lead carbonates.

pubmed23n0045_10934

Asthma in the 1990s. A new approach to therapy.

Asthma has been shown to be an inflammatory disease. Therefore, it makes sense to base treatment strategies on the selection of an appropriate anti-inflammatory agent, with bronchodilators being used as effective rescue medications. Because of recent concerns raised in the literature about the safety of long-term use of beta 2 agonists, early and appropriate medication in the form of inhaled corticosteroids or cromolyn sodium is recommended for daily control of asthma symptoms, long-term patient management, and prevention of acute exacerbations.

Asthma in the 1990s. A new approach to therapy. Asthma has been shown to be an inflammatory disease. Therefore, it makes sense to base treatment strategies on the selection of an appropriate anti-inflammatory agent, with bronchodilators being used as effective rescue medications. Because of recent concerns raised in the literature about the safety of long-term use of beta 2 agonists, early and appropriate medication in the form of inhaled corticosteroids or cromolyn sodium is recommended for daily control of asthma symptoms, long-term patient management, and prevention of acute exacerbations.

pubmed23n1009_600

[Stereotactic Biopsy in the Lateral Position Using a Neuronavigation System].

Stereotactic brain biopsy using a navigation system is minimally invasive because it can be performed under local anesthesia. However, there are problems due to the localization and accessibility of the tumor and instability of the airway under sedation. This study aimed to examine the differences in safety and surgical time between the supine and lateral position. This study included 25 cases which underwent navigation-guided brain biopsies from May 2015 to March 2018 in the Kanazawa University Hospital. We compared tumor localization, operation time, standby time, intraoperative difficulties, and final diagnosis acquisition rates between the supine and lateral positions. Puncture sites were then examined by visualizing all biopsy trajectories simultaneously on a three-dimensional cerebral template. Biopsies of the tumor in all cerebrum lobes were possible in the lateral position. There were no significant differences in operating time or standby time between the supine and lateral positions. One case in the spine position required sedation by an anesthesiologist due to body movement, but there were no difficulties in any cases of lateral positioning. The final diagnosis acquisition rate was 100% in all cases. In the lateral position, stable breathing was maintained because the head and the trunk axes remined in the same line. Stereotactic brain biopsy in the lateral position can be safer and more useful than in the supine position under local anesthesia.

[Stereotactic Biopsy in the Lateral Position Using a Neuronavigation System]. Stereotactic brain biopsy using a navigation system is minimally invasive because it can be performed under local anesthesia. However, there are problems due to the localization and accessibility of the tumor and instability of the airway under sedation. This study aimed to examine the differences in safety and surgical time between the supine and lateral position. This study included 25 cases which underwent navigation-guided brain biopsies from May 2015 to March 2018 in the Kanazawa University Hospital. We compared tumor localization, operation time, standby time, intraoperative difficulties, and final diagnosis acquisition rates between the supine and lateral positions. Puncture sites were then examined by visualizing all biopsy trajectories simultaneously on a three-dimensional cerebral template. Biopsies of the tumor in all cerebrum lobes were possible in the lateral position. There were no significant differences in operating time or standby time between the supine and lateral positions. One case in the spine position required sedation by an anesthesiologist due to body movement, but there were no difficulties in any cases of lateral positioning. The final diagnosis acquisition rate was 100% in all cases. In the lateral position, stable breathing was maintained because the head and the trunk axes remined in the same line. Stereotactic brain biopsy in the lateral position can be safer and more useful than in the supine position under local anesthesia.

pubmed23n0610_11773

Early perceptions of an epidemic.

This article surveys some descriptions of the Fore people made on early contact in the 1950s by patrol officers, social anthropologists and medical doctors. Sorcery accusations and cannibalism initially impressed these outside observers, though gradually they came to realize that a strange and fatal condition called kuru was a major affliction of the Fore, especially women and children. Fore attributed kuru to sorcery, anthropologists speculated on psychosomatic causes and medical officers began to wonder if it was a mysterious encephalitis.

Early perceptions of an epidemic. This article surveys some descriptions of the Fore people made on early contact in the 1950s by patrol officers, social anthropologists and medical doctors. Sorcery accusations and cannibalism initially impressed these outside observers, though gradually they came to realize that a strange and fatal condition called kuru was a major affliction of the Fore, especially women and children. Fore attributed kuru to sorcery, anthropologists speculated on psychosomatic causes and medical officers began to wonder if it was a mysterious encephalitis.

pubmed23n0529_13405

Effects of in vitro preculture on in vivo development of human engineered cartilage in an ectopic model.

We investigated whether, and under which conditions (i.e., cell-seeding density, medium supplements), in vitro preculture enhances in vivo development of human engineered cartilage in an ectopic nude mouse model. Monolayer-expanded adult human articular chondrocytes (AHACs) were seeded into Hyalograft C disks at 1.3 x 10(7) cells/cm3 (low density) or 7.6 x 10(7) cells/cm3 (high density). Constructs were directly implanted subcutaneously in nude mice for up to 8 weeks or precultured for 2 weeks before implantation. Preculture medium contained either transforming growth factor-beta1 (TGF-beta1, 1 ng/mL), fibroblast growth factor-2, and platelet-derived growth factor (proliferating medium) or TGF-beta1 (10 ng/mL) and insulin (differentiating medium). Both in vitro and after in vivo implantation, constructs derived by cell seeding at high versus low density and precultured in differentiating versus proliferating medium generated more cartilaginous tissues containing higher amounts of glycosaminoglycan and collagen type II and lower amounts of collagen type I, and with higher equilibrium moduli. As compared with direct implantation of freshly seeded scaffolds, preculture of AHAC-Hyalograft C constructs in differentiating medium, but not in proliferating medium, supported enhanced in vivo development of engineered cartilage. The effect of preculture was more pronounced when constructs were seeded at low density as compared with high density. This study indicates that preculture of human engineered cartilage in differentiating medium has the potential to provide grafts with higher equilibrium moduli and enhanced in vivo developmental capacity than freshly seeded scaffolds. These findings need to be validated in an orthotopic model system.

Effects of in vitro preculture on in vivo development of human engineered cartilage in an ectopic model. We investigated whether, and under which conditions (i.e., cell-seeding density, medium supplements), in vitro preculture enhances in vivo development of human engineered cartilage in an ectopic nude mouse model. Monolayer-expanded adult human articular chondrocytes (AHACs) were seeded into Hyalograft C disks at 1.3 x 10(7) cells/cm3 (low density) or 7.6 x 10(7) cells/cm3 (high density). Constructs were directly implanted subcutaneously in nude mice for up to 8 weeks or precultured for 2 weeks before implantation. Preculture medium contained either transforming growth factor-beta1 (TGF-beta1, 1 ng/mL), fibroblast growth factor-2, and platelet-derived growth factor (proliferating medium) or TGF-beta1 (10 ng/mL) and insulin (differentiating medium). Both in vitro and after in vivo implantation, constructs derived by cell seeding at high versus low density and precultured in differentiating versus proliferating medium generated more cartilaginous tissues containing higher amounts of glycosaminoglycan and collagen type II and lower amounts of collagen type I, and with higher equilibrium moduli. As compared with direct implantation of freshly seeded scaffolds, preculture of AHAC-Hyalograft C constructs in differentiating medium, but not in proliferating medium, supported enhanced in vivo development of engineered cartilage. The effect of preculture was more pronounced when constructs were seeded at low density as compared with high density. This study indicates that preculture of human engineered cartilage in differentiating medium has the potential to provide grafts with higher equilibrium moduli and enhanced in vivo developmental capacity than freshly seeded scaffolds. These findings need to be validated in an orthotopic model system.