Activation of peroxisome proliferator-activated receptors by chlorinated hydrocarbons and endogenous steroids.

Trichloroethylene (TCE) and related hydrocarbons constitute an important class of environmental pollutants whose adverse effects on liver, kidney, and other tissues may, in part, be mediated by peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors belonging to the steroid receptor superfamily. Activation of PPAR induces a dramatic proliferation of peroxisomes in rodent hepatocytes and ultimately leads to hepatocellular carcinoma. To elucidate the role of PPAR in the pathophysiologic effects of TCE and its metabolites, it is important to understand the mechanisms whereby PPAR is activated both by TCE and endogenous peroxisome proliferators. The investigations summarized in this article a) help clarify the mechanism by which TCE and its metabolites induce peroxisome proliferation and b) explore the potential role of the adrenal steroid and anticarcinogen dehydroepiandrosterone 3beta-sulfate (DHEA-S) as an endogenous PPAR activator. Transient transfection studies have demonstrated that the TCE metabolites trichloroacetate and dichloroacetate both activate PPAR alpha, a major liver-expressed receptor isoform. TCE itself was inactive when tested over the same concentration range, suggesting that its acidic metabolites mediate the peroxisome proliferative potential of TCE. Although DHEA-S is an active peroxisome proliferator in vivo, this steroid does not stimulate trans-activation of PPAR alpha or of two other PPAR isoforms, gamma and delta/Nuc1, when evaluated in COS-1 cell transfection studies. To test whether PPAR alpha mediates peroxisomal gene induction by DHEA-S in intact animals, DHEA-S has been administered to mice lacking a functional PPAR alpha gene. DHEA-S was thus shown to markedly increase hepatic expression of two microsomal P4504A proteins associated with the peroxisomal proliferative response in wild-type mice. In contrast, DHEA-S did not induce these hepatic proteins in PPAR alpha-deficient mice. Thus, despite its unresponsiveness to steroidal peroxisome proliferators in transfection assays, PPAR alpha is an obligatory mediator of DHEA-S-stimulated hepatic peroxisomal gene induction. DHEA-S, or one of its metabolites, may thus serve as an important endogenous regulator of liver peroxisomal enzyme expression

The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school

Determinants of career aspirations of medical students in southern China

<p>Abstract</p> <p>Background</p> <p>With recent changes in both the Chinese medical system and compensation of medical doctors, the career aspirations of Chinese medical students have become more diverse. Shantou University Medical College has conducted evaluations and instituted programs to enhance student preparedness to enter a variety of medical careers.</p> <p>Methods</p> <p>A survey was conducted with 85 students to evaluate medical career aspirations and their association with family background, personal skills, English language proficiency, and interest in biomedical research, which were considered as possible factors affecting their career interest.</p> <p>Results</p> <p>Chinese students aspire to traditional as well as nontraditional medical careers. A significant minority of students are now interested in nontraditional careers such as medical teaching or research. However, poor proficiency in the English language and lack of computer skills may limit their academic and career opportunities.</p> <p>Conclusion</p> <p>Career aspirations have changed among medical undergraduates. Although many wish to pursue a traditional clinical doctor career, many are interested in research and teaching careers. Factors such as family background, personal characteristics, school mentoring, and extracurricular support may play a role.</p

General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries

BACKGROUND: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada. METHODOLOGY/PRINCIPAL FINDINGS: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently. CONCLUSIONS: This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research

Decentralization's impact on the health workforce: Perspectives of managers, workers and national leaders

Designers and implementers of decentralization and other reform measures have focused much attention on financial and structural reform measures, but ignored their human resource implications. Concern is mounting about the impact that the reallocation of roles and responsibilities has had on the health workforce and its management, but the experiences and lessons of different countries have not been widely shared. This paper examines evidence from published literature on decentralization's impact on the demand side of the human resource equation, as well as the factors that have contributed to the impact. The elements that make such an impact analysis exceptionally complex are identified. They include the mode of decentralization that a country is implementing, the level of responsibility for the salary budget and pay determination, and the civil service status of transferred health workers. The main body of the paper is devoted to examining decentralization's impact on human resource issues from three different perspectives: that of local health managers, health workers themselves, and national health leaders. These three groups have different concerns in the human resource realm, and consequently, have been differently affected by decentralization processes. The paper concludes with recommendations regarding three key concerns that national authorities and international agencies should give prompt attention to. They are (1) defining the essential human resource policy, planning and management skills for national human resource managers who work in decentralized countries, and developing training programs to equip them with such skills; (2) supporting research that focuses on improving the knowledge base of how different modes of decentralization impact on staffing equity; and (3) identifying factors that most critically influence health worker motivation and performance under decentralization, and documenting the most cost-effective best practices to improve them. Notable experiences from South Africa, Ghana, Indonesia and Mexico are shared in an annex

Population dynamics of Neisseria gonorrhoeae in Shanghai, China: a comparative study

<p>Abstract</p> <p>Background</p> <p>Gonorrhea is a major sexually transmitted disease (STD) in many countries worldwide. The emergence of fluoroquinolone resistance has complicated efforts to control and treat this disease. We report the first study of the evolutionary processes acting on transmission dynamics of a resistant gonococcal population from Shanghai, China. We compare these findings with our previous study of the evolution of a fluoroquinolone sensitive gonococcal population from Baltimore, MD.</p> <p>Methods</p> <p>Ninety six gonococcal samples were collected from male patients in Shanghai, China. All samples were fluoroquinolone resistant. Seven MLST housekeeping genes, two fluoroquinolone resistance genes (<it>gyrA </it>and <it>parC</it>) and the <it>porB </it>gene were sequenced and subjected to population genetic and evolutionary analyses. We estimated genetic diversity, recombination, growth, and selective pressure. The evolutionary history and population dynamics of the Shanghai population were also inferred and compared with that observed in a fluoroquinolone sensitive gonococcal population from Baltimore.</p> <p>Results</p> <p>For both populations, mutation plays a larger role than recombination in the evolution of the <it>porB </it>gene, whereas the latter seems to be the main force driving the evolution of housekeeping and fluoroquinolone resistance genes. In both populations there was evidence for positively selected sites in all genes analyzed. The phylogenetic analyses showed no temporal clustering in the Shanghai gonococcal population, nor did we detect shared allelic profiles between the Shanghai and the Baltimore populations. Past population dynamics of gonococcal strains from Shanghai showed a rising relative effective population size (Ne) in MLST genes with a declining relative Ne for <it>gyrA </it>and <it>parC</it>, whereas among sensitive strains from Baltimore we previously observed concordance among these genes. In both Shanghai and Baltimore, the past population dynamics of gonococcal strains tracked changes in the prevalence of gonorrhea.</p> <p>Conclusions</p> <p>Our study illustrates both similarities and differences in the evolutionary processes acting on gonococcal populations in different geographic areas. An explanation of this pattern that may apply in China is the continued use of quinolone antibiotics despite widespread resistance. Population genetic analysis of gonococcal strains in conjunction with epidemiological surveillance may provide insights into the epidemic behavior of antibiotic resistant strains and help to design control measures.</p

DreamTel; Diabetes risk evaluation and management tele-monitoring study protocol

<p>Abstract</p> <p>Background</p> <p>The rising prevalence of type 2 diabetes underlines the importance of secondary strategies for the prevention of target organ damage. While access to diabetes education centers and diabetes intensification management has been shown to improve blood glucose control, these services are not available to all that require them, particularly in rural and northern areas. The provision of these services through the Home Care team is an advance that can overcome these barriers. Transfer of blood glucose data electronically from the home to the health care provider may improve diabetes management.</p> <p>Methods and design</p> <p>The study population will consist of patients with type 2 diabetes with uncontrolled A1c levels living on reserve in the Battlefords region of Saskatchewan, Canada. This pilot study will take place over three phases. In the first phase over three months the impact of the introduction of the Bluetooth enabled glucose monitor will be assessed. In the second phase over three months, the development of guidelines based treatment algorithms for diabetes intensification will be completed. In the third phase lasting 18 months, study subjects will have diabetes intensification according to the algorithms developed.</p> <p>Discussion</p> <p>The first phase will determine if the use of the Bluetooth enabled blood glucose devices which can transmit results electronically will lead to changes in A1c levels. It will also determine the feasibility of recruiting subjects to use this technology. The rest of the Diabetes Risk Evaluation and Management Tele-monitoring (DreamTel) study will determine if the delivery of a diabetes intensification management program by the Home Care team supported by the Bluetooth enabled glucose meters leads to improvements in diabetes management.</p> <p>Trial Registration</p> <p>Protocol NCT00325624</p

Risk Behaviors for Reproductive Tract Infection in Women Who Have Sex with Women in Beijing, China

OBJECTIVES: To assess risk behaviors for reproductive tract infections (RTI) including sexually transmitted infections (STI) among women who have sex with women (WSW) in Beijing, China. METHODS: A cross-sectional study of women recruited from venues and internet outreach analyzed using interviews. RESULTS: We recruited 224 WSW, among whom were 37 couples. The average age of participants was 25.6 years. Sex with men in the past year was reported by 10.7% of participants. During the past year, 34.3% (77/224) had had >1 sexual partner and 72.4% (162/224) had ever had >1 sexual partner. Condom use in the last sex with a man was reported by 54.2% (13/24) of women; 12.5% (3/24) reported never having used a condom with a man in the past year. In the past year, 13.4% (30/224) reported using sex toys with their female partners; of these, 43.3% (13/30) reported consistent condom use with the sex toys and 36.7% (11/30) had shared sex toys. Among participants 65.2% (120/184) reported that their "G-spot" had been stimulated during sex, 49.2% (59/120) of whom reported bleeding during or after sex. Only 12.5% (8/64) of those never reporting "G spot" stimulation reported bleeding during or after sex (P<0.001). CONCLUSIONS: WSW in Beijing engaged in high-risk sexual behaviors that may carry a substantial risk of being infected with STI/RTI. To implement STI/RTI prevention and intervention among women, women-women sexual behavior should be considered when doing research and intervention programs