Human vaginal microbiota colonization is regulated by female sex hormones in a mouse model.

Introduction: Clinically, a Lactobacillus rich vaginal microbiota (VMB) is considered optimal for reproductive outcomes, while a VMB populated by anaerobes is associated with dysbiosis and the clinical condition bacterial vaginosis (BV), which is linked to increased susceptibility to sexually transmitted infections and adverse reproductive outcomes. Mouse models that mimic eubiotic and dysbiotic VMB are currently lacking but could play a critical role in improving protective interventions. Methods: In this study, probiotic, eubiotic, and dysbiotic models were developed in C57BL/6 mice, using probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, eubiotic Lactobacillus crispatus, or dysbiotic Gardnerella vaginalis strains. Endogenous sex hormones were manipulated by either ovariectomizing (OVX) mice or administering 17ß-estradiol or progesterone pellets in OVX mice. Hormone-altered mice were inoculated with probiotic Lactobacillus species, L. crispatus, or G. vaginalis, and colonization was tracked using quantitative plating assays. Glycogen and MUC-1 levels in hormone-treated mice were determined with ELISA and MUC-1 staining. Results: Following a single administration, L. rhamnosus and L. reuteri persisted in the mouse vaginal tract for up to eight days, L. crispatus persisted for up to three days, and G. vaginalis persisted for up to two days, as measured by quantitative plating assays and qPCR. Colonization of G. vaginalis was facilitated by the presence of mucin. The lack of endogenous hormones in OVX mice dramatically decreased VMB bacterial load compared to normal mice. None of the exogenous bacteria including Lactobacilli could colonize OVX mice for more than 24 hours. Treatment with 17ß-estradiol but not progesterone restored the endogenous VMB and colonization with Lactobacilli and G. vaginalis. Interestingly, 17ß-estradiol treated mice had significantly increased levels of glycogen compared to OVX and progesterone-treated mice. Discussion: Based on the results, we have shown that estrogen played a significant role in the ability for human VMB species to colonize in our mouse models, potentially through a glycogen mediated mechanism. These results suggest there is a dynamic interaction between sex hormones and the VMB, which can affect bacterial diversity and the ability for a VMB to colonize.

Metabolic signature for a dysbiotic microbiome in the female genital tract: A systematic review and meta-analysis.

BACKGROUND: The vaginal microbiome (VMB) is a critical determinant of reproductive health, where a microbial shift towards a dysbiotic environment has implications for susceptibility to, and clinical presentation of sexually transmitted infections (STIs). Metabolomic profiling of the vaginal microenvironment has led to the identification of metabolic responses to clinical conditions of dysbiosis. However, no studies have examined metabolic markers that are common across conditions and can serve as a signature for vaginal dysbiosis. METHOD OF STUDY: We have conducted a comprehensive systematic review and meta-analysis to identify consistently deregulated metabolites along with their impact on host and microbial metabolism during dysbiosis. We employed two complementary approaches including a vote counting analysis for all eligible studies identified in the systematic review, in addition to a meta-analysis for a subset of studies with sufficient available data. Significantly deregulated metabolites were then selected for pathway enrichment analysis. RESULTS: Our results revealed a total of 502 altered metabolites reported across 10 dysbiotic conditions from 16 studies. Following a rigorous, collective analysis, six metabolites which were consistently downregulated and could be generalized to all dysbiotic conditions were identified. In addition, five downregulated and one upregulated metabolite was identified from a bacterial vaginosis (BV) focused sub-analysis. These metabolites have the potential to serve as a metabolic signature for vaginal dysbiosis. Their role in eight altered metabolic pathways indicates a disruption of amino acid, carbohydrate, and energy metabolism during dysbiosis. CONCLUSION: Based on this analysis, we propose a schematic model outlining the common metabolic perturbations associated with vaginal dysbiosis, which can be potential targets for therapeutics and prophylaxis.

Determinants of neural tube defect (NTD)-protective circulating concentrations of folate in women of child-bearing age in the US post-folic acid fortification era.

We evaluated folate status of child-bearing age women diagnosed with abnormal pap smear in the US post-folic acid (FA) fortification era and assessed the determinants of NTD-protective and supra-physiologic (SP) concentrations of folate. The distribution of 843 women according to NTD-protective concentrations of RBC folate, plasma folate and SP concentrations of plasma folate were tested in relation to demographic and life-style factors. Logistic regression models specified NTD-protective concentrations of RBC and plasma folate or SP concentrations of plasma folate as dependent variables and demographic and life-style factors as independent predictors of interest. More than 82% reached NTD-protective concentrations of RBC and plasma folate and ~30% reached SP concentrations of plasma folate. FA supplement use was associated with having SP concentrations of plasma folate rather than NTD-protective concentrations of folate. African American (AA) women and smokers were significantly less likely to achieve NTD-protective concentrations of RBC and plasma folate. A large majority of women reached NTD-protective concentrations of folate with the current level of FA fortification without using supplementary FA. Therefore, the remaining disparities in AA women and in smokers should be addressed by targeted individual improvements in folate intake.

PubMed-based quantitative analysis of biomedical publications in the SAARC countries: 1985-2009.

OBJECTIVE: To conduct a geographical analysis of biomedical publications from the South Asian Association for Regional Cooperation (SAARC) countries over the past 25 years (1985-2009) using the PubMed database. STUDY DESIGN: A qualitative study. PLACE AND DURATION OF STUDY: Web-based search during September 2010. METHODOLOGY: A data extraction program, developed by one of the authors (SFS), was used to extract the raw publication counts from the downloaded PubMed data. A search of PubMed was performed for all journals indexed by selecting the advanced search option and entering the country name in the 'affiliation' field. The publications were normalized by total population, adult illiteracy rate, gross domestic product (GDP), secondary school enrollment ratio and Internet usage rate. RESULTS: The number of PubMed-listed papers published by the SAARC countries over the last 25 years totalled 141,783, which is 1.1% of the total papers indexed by PubMed in the same period. India alone produced 90.5% of total publications generated by SAARC countries. The average number of papers published per year from 1985 to 2009 was 5671 and number of publication increased approximately 242-fold. Normalizing by the population (per million) and GDP (per billion), India (133, 27.6%) and Nepal (323, 37.3%) had the highest publications respectively. CONCLUSION: There was a marked imbalance among the SAARC countries in terms of biomedical research and publication. Because of huge population and the high disease burden, biomedical research and publication output should receive special attention to formulate health policies, re-orient medical education curricula, and alleviate diseases and poverty.

Career choices among medical students in Bangladesh.

INTRODUCTION: Information regarding career choices of medical students is important to plan human resources for health, design need-based educational programs, and ensure equitable and quality health care services in a country. AIM: The aim of the study is to identify career choices, nature of career, intended practice locations, and reasons for career choices of Bangladesh medical students. METHOD: First-, third-, and fifth-year students of Bangladesh Medical College and Uttara Adhunik Medical College completed a self-report questionnaire on career choices, nature of career, intended practice locations, and reasons for career choices. The students were requested to choose three long-term choices from the given specialties. RESULTS: A total of 132 students responded (46 males and 86 females) and response rate was 75%. The popular choices (first choice) among males and females were medical specialty, surgical specialty, obstetrics and gynecology, and general practice. For first, second, and third choices altogether, male students chose surgical specialties and female students preferred medical specialties. The leading reasons for selecting a specialty were personal interest and wide job opportunity. More than 67% of respondents wanted to join private services and about 90% chose major cities as practice locations. About 43% of respondents expressed willingness to practice medicine in Bangladesh, whereas 51% of total respondents wanted to practice abroad. DISCUSSION: Majority of students intended to specialize in established clinical specialties and subsequently practice in major cities, and more than half wanted to immigrate to other countries. Basic medical subjects and service-oriented (lifestyle-related) and preventive/social medical specialties were found to be less attractive. If this pattern continues, Bangladesh will suffer a chronic shortage of health personnel in certain specialties and in rural areas. CONCLUSIONS: Reorientation of health care and medical education is needed along with policy settings to attract doctors to the scarcity and high-priority disciplines so that imbalances encountered would be minimal in future.

Physician participation in clinical research and trials: issues and approaches.

The rapid development of new drugs, therapies, and devices has created a dramatic increase in the number of clinical research studies that highlights the need for greater participation in research by physicians as well as patients. Furthermore, the potential of clinical research is unlikely to be reached without greater participation of physicians in research. Physicians face a variety of barriers with regard to participation in clinical research. These barriers are system-or organization-related as well as research-and physician-related. To encourage physician participation, appropriate organizational and operational infrastructures are needed in health care institutes to support research planning and management. All physicians should receive education and training in the fundamentals of research design and methodology, which need to be incorporated into undergraduate medical education and postgraduate training curricula and then reinforced through continuing medical education. Medical schools need to analyze current practices of teaching-learning and research, and reflect upon possible changes needed to develop a 'student-focused teaching-learning and research culture'. This article examines the barriers to and benefits of physician participation in clinical research as well as interventions needed to increase their participation, including the specific role of undergraduate medical education. The main challenge is the unwillingness of many physicians and patients to participate in clinical trials. Barriers to participation include lack of time, lack of resources, trial-specific issues, communication difficulties, conflicts between the role of clinician and scientist, inadequate research experience and training for physicians, lack of rewards and recognition for physicians, and sometimes a scientifically uninteresting research question, among others. Strategies to encourage physician participation in clinical research include financial and nonfinancial incentives, adequate training, research questions that are in line with physician interests and have clear potential to improve patient care, and regular feedback. Finally, encouraging research culture and fostering the development of inquiry and research-based learning among medical students is now a high priority in order to develop more and better clinician-researchers.