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Spermatogonial stem cells (SSCs) are the foundation for spermatogenesis and, thus, preservation of a species. Because of stem cell rarity, studying their self-renewal is greatly facilitated by in vitro culture of enriched biologically active cell populations. A recently developed culture method identified glial cell line-derived neurotrophic factor (GDNF) as the essential growth factor that supports in vitro self-renewal of SSC5 and results in an increase in their number. This system is a good model to study mechanisms of stem cell self-renewal because of the well defined culture conditions, enriched cell population, and available transplantation assay. By withdrawing and replacing GDNF in culture medium, we identified regulated expression of many genes by using microarray analysis. The expression levels of six of these genes were dramatically decreased by GDNF withdrawal and increased by GDNF replacement. To demonstrate the biological significance of the identified GDNF-regulated genes, we examined the importance of the most responsive of the six, bcl6b, a transcriptional repressor. By using siRNA to reduce transcript levels, Bcl6b was shown to be crucial for SSC maintenance in vitro. Moreover, evaluation of Bcl6b-null male testes revealed degeneration and/or absence of active spermatogenesis in 24 ± 7% of seminiferous tubules. These data suggest that Bcl6b is an important molecule in SSC self-renewal and validate the biological relevance of the GDNF-regulated genes identified through microarray analysis. In addition, comparison of data generated in this study to other stem cell types suggests that self-renewal in SSCs is regulated by distinctly different molecular mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: The goals of this study were to develop and determine the feasibility of interventions designed to increase both primary care physician implementation of and patient adherence to recommendations from ambulatory-based consultative comprehensive geriatric assessment (CGA), and to identify sociodemographic and intervention-related predictors of physician and patient adherence.Patients and Methods: One hundred thirty-nine community-dwelling older persons who failed a screen for functional impairment, depressive symptoms, falls, or urinary incontinence received outpatient CGA consultation. These patients and the 115 physicians who provided primary care for them received one of three adherence interventions, each of which had a physician education component and a patient education and empowerment component. Recommendations were classified as physician-initiated or self-care and as "major" or "minor"; one was deemed "most important". Adherence rates were determined on the basis of face-to-face interviews with patients.Results: Based on 528 recommendations for 139 subjects, physician implementation of "most important" recommendations was 83% and of major recommendations was 78.5%. Patient adherence with physician-initiated "most important" and "major" recommendations were 81.8% and 78.8% respectively. In multivariate models, only the status of the recommendation of "most important" (odds ratio 2.4, 95% CI [confidence interval] 1.3 to 4.5) and health maintenance organization (HMO) status of the patient (odds ratio 2.1, 95% CI 1.3 to 3.6) remained significant in predicting physician implementation. The logistic model predicting patient adherence to physician-initiated recommendations included male patient gender (odds ratio 3.1, 95% CI 1.3 to 7.0), the status of the recommendation of "most important" (odds ratio 1.9, 95% CI 1.0 to 3.8), total number of recommendations (odds ratio 0.7, 95% CI 0.5 to 0.9), and total number of problems identified by CGA (odds ratio 1.8, 95% CI 1.2 to 2.7).Conclusions: These findings indicate that relatively modest interventions strategies are feasible and lead to high levels of physician implementation of and patient adherence to physician-initiated CGA recommendations. These interventions appear to be particularly effective in HMO patients and for recommendations that were deemed to be "most important". [ABSTRACT FROM AUTHOR]

Background: Cardiovascular illness may partly explain why patients with schizophrenia die at least 20 years earlier than general population. Monitoring and screening for cardiovascular risk factors was recently recommended in schizophrenia treatment guidelines. High-sensitivity C-reactive protein (hsCRP) is one of the inflammation mediators that has been widely used as a biomarker for predicting the occurrence of future cardiovascular (incl. thromboembolism) events in somatic medicine, but not in psychiatry. Methods: In the prospective ANTRE (ANtipsychotics ThRombosis Embolism) study we investigated the plasma levels of hsCRP and lipids and measured weight and BMI (Body Mass Index) in a group of thirty patients (seventeen males and thirteen females) with newly diagnosed psychosis (mean age 28.2±8.0, range 18–52 years). Control group consisted of thirty-one healthy volunteers matched for age, gender and body mass index. We evaluated the haemostatic parameters at the time of admission and after three and twelve months during antipsychotic treatment. Results: Weight (mean 67.6 versus 77.2; P=0.00002), BMI (median 21.6 versus 26.1; P=0.001), hsCRP (median 1.0 versus 2.5; P=0.0009), total cholesterol (4.6 versus 5.3; P=0.016) and atherogenity index (2.1 versus 3.0; P=0.016) were significantly increased in the study group compared to controls. Conclusions: We found increased markers of cardiovascular risk in patients with psychosis during first year of treatment. Particularly increase of hsCRP may be associated with cardiovascular events in schizophrenia patients. [ABSTRACT FROM AUTHOR]

Introduction: Patients with schizophrenia have an increased risk of venous thromboembolism (VTE). The increased risk is more marked among new users and those prescribed atypical antipsychotic drugs. Platelet activation, changes of plasma coagulation, or fibrinolysis are likely to be responsible for the increase in thrombotic events. Methods: In the prospective ANTRE (ANtipsychotics ThRombosis Embolism) study we investigated the plasma levels of markers indicating activation of platelets (soluble P-selectin), coagulation (factor VIII) and fibrinolysis (D-dimers) in a group of thirty patients (seventeen males) with newly diagnosed psychosis (mean age 28.2, range 18–52 years) and in thirty-one healthy volunteers who were matched for age, gender and body mass index. We measured the haemostatic parameters at the time of patients’ admission) and after three and twelve months during outpatient antipsychotic treatment. Results: At baseline there were significantly increased plasma levels of sP-selectin (P=0.0003), D-dimers (P=0.0007) and factor VIII (P=0.0076) in the group of patients with acute psychosis as compared to healthy volunteers. After three and twelve months of patients’ follow up we still observed increased levels of sP-selectin and D-dimers. Plasma levels of factor VIII were significantly increased after 3 months, but decreased after 12 months. Conclusions: We found an increase in markers of activation of haemostasis in patients in acute as well as in chronic stage of psychosis. Our results could explain the possible pathological mechanisms of VTE that are independent from antipsychotic treatment and play a role mainly in the acute phase of the disease. [ABSTRACT FROM AUTHOR]

Objectives: Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism (VTE) in schizophrenia. The aim of the study was to ascertain whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication. Methods: We investigated plasma levels of markers indicating activation of coagulation (D-dimers) and platelets (solubile P-selectin, sP-selectin) in a group of nine men and nine women with acute schizophrenia who had not yet been treated with antipsychotics (age 29.8±9.1 years; body mass index 23.3±5.1), and eighteen healthy volunteers matched for age, gender and body mass index. Results: D-dimers (median 0.38 vs 0.22 mg/l; P=0.049) as well as sP-selectin (median 195.9 vs 111.9 ng/ml; P=0.008) plasma levels were significantly increased in the group of patients with acute schizophrenia as compared to healthy volunteers. Conclusions: The results suggest that at least a part of venous thromboembolic events in patients with schizophrenia may rather be induced by pathogenetic mechanisms related to psychosis than caused by antipsychotic treatment. Finding an exact cause of VTE in schizophrenia is necessary for its efficient treatment and prevention. We are aware of the pilot character of our data, and continue to involve more patients and healthy volunteers into the research. [Copyright &y& Elsevier]

Introduction: Patients with schizophrenia have at least 20 years shorter life spam compared with general population that is primarily caused by their cardiovascular morbidity. Aims: The aim of this cross-sectional study was to assess the prevalence of cardiometabolic risk factors in a sample of Czech patients with schizophrenia and related diseases and to predict a risk of premature cardiovascular mortality in this population. Methods: We reviewed data from 129 outpatients treated in specialized outpatient clinic for psychoses. The main collected variables included basic physical parameters (height, weight, waist circumference, blood pressure), smoking habits, laboratory data (glucose level, serum lipids levels) and ECG. Finally, we compared the studied group with a matched sample from general population in Czech Republic regarding the cardiovascular risk factors. Results: Our results show that the most prevalent risk factors are overweight (70% of patients have BMI over 25), dyslipidaemia (70% of patients) and smoking (43% of patients). According to SCORE diagram, there is a high risk of fatal cardiovascular event in ten years in 10% of the study group. The percentage gets even higher (up to 24%) when the latest European guidelines for cardiovascular disease prevention were used to calculate the risk. Conclusions: Our outcomes indicate even higher cardiometabolic morbidity in patients with psychoses than referred in literature. [ABSTRACT FROM AUTHOR]

Viewing primary care as a niche in a medical system is incorrect for the US. Its role should be as a system filter, to be cost-effective, and to be accessible to people. Its position should be as a central hub in healthcare systems. It is important that health systems realize the essential integrative function of primary care. [ABSTRACT FROM AUTHOR]

Purpose: To identify and examine religious and spiritual coping strategies among elderly women with newly diagnosed breast cancer.Methods: A convenience sample of 33 women age 65 years was recruited within 6 months of diagnosis. Respondents participated in a structured interview with open-ended questions. Transcripts of the interviews were analysed independently by three researchers and themes were discussed until consensus was reached.Results: Participants' religious background was varied: 17 Protestant, five Catholic, six Jews, and four Other. There was great variation in the frequency of religious service attendance. Religious and/or spiritual belief either increased or stayed the same during the time of health crisis. Analysis of transcripts revealed three themes. Religious and spiritual faith provided respondents with the emotional support necessary to deal with their breast cancer (91%), with social support (70%), and with the ability to make meaning in their everyday life, particularly during their cancer experience (64%).Conclusions: Religious and spiritual faith provides elderly women newly diagnosed with breast cancer with important tools for coping with their illness and should be recognized by diagnosing physicians. It may be important to encourage these patients to seek religious support and/or to reconnect with their religious community. [ABSTRACT FROM AUTHOR]

Background: In consultative models of Comprehensive Geriatric Assessment (CGA), lack of implementation of CGA recommendations is well documented and appears to be a potential explanation for negative findings. The purpose of this study is to identify patient determinants of adherence to recommendations received from a community-based CGA consultative model program.Methods: Subjects (N = 139) received self-care and/or physician-initiated CGA recommendations and were interviewed three months later to determine adherence with the most important recommendation, and health belief, communication, and social support factors associated with adherence. Independent variables were organized into the Andersen Behavioral Model for analysis.Results: At the bivariate level, one predisposing factor (intention) and six enabling factors (low difficulty level, high support, high utility, high self-efficacy, agreement on the importance of the recommendation and good specific communication about the recommendation) were significant determinants of adherence. Two functional health measures and seriousness of the target condition of the recommendation were significant need factors. In the final logistic regression model, one predisposing variable (intention), one enabling variable (utility), and one need factor (high functional status), and two interaction terms significantly predicted adherence.Conclusion: CGA recommendations that are seen as worthwhile, not too much trouble, and able to be accomplished are the most likely to be initiated. Older adults with relatively higher functional levels are also more likely to follow through with CGA recommendations even though their needs may be lower. We found the Andersen Behavioral Model useful in the analysis of factors associated with adherence behavior to consultative CGA recommendations. [ABSTRACT FROM AUTHOR]