Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men

The effect of physical activity on psychological distress, cortisol and obesity: results of the farming fit intervention program

Background:Rural and regional Australians have a higher likelihood of mental illness throughout their lifetime than people living in major cities, although the underlying reasons are not yet well defined. Additionally, rural populations experience more lifestyle associated co-morbidities including obesity, diabetes and cardiovascular disease. Research conducted by the National Centre for Farmer Health between 2004 and 2009 revealed a positive correlation between obesity and psychological distress among the farming community. Chronic stress is known to overstimulate the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol secretion which are associated with abdominal adiposity. Increasing physical activity may normalise cortisol secretion and thereby positively impact both physical and mental health. This paper assesses the effects of increasing physical activity on obesity, health behaviors and mental health in Victorian farming men and women.Methods:Farming Fit was a six month quasi-experimental (convenience sample) longitudinal design control-intervention study. Overweight or obese (BMI ?25?kg/m2) farm men (n?=?43) and women (n?=?29) were recruited with demographic, health behaviors, anthropometric, blood pressure and biochemistry data collected at baseline and at a six months. Salivary cortisol and depression anxiety stress scale results were collected at baseline, three and six months. The intervention group (n?=?37) received a personalized exercise program and regular phone coaching to promote physical activity.Results:The intervention group showed significant reductions in body weight and waist circumference. Results indicated that following the six month exercise program, the intervention group were 2.64???0.65?kg lighter (p?<?0.001), had reduced waist circumference by 2.01???0.86?cm (p?=?0.02) and BMI by 0.97???0.22?kg/m2 (p?<?0.001) relative to the control group.Conclusion:Increasing physical activity altered measures of obesity in farm men and women but did not affect mental health measures or cortisol secretion levels

Reducing psychological distress and obesity in Australian farmers by promoting physical activity

Background: Studies have confirmed that the rate of mental illness is no higher in rural Australians than that of urban Australians. However, the rate of poor mental health outcomes, and in particular suicide, is significantly raised in rural populations. This is thought to be due to lack of early diagnosis, health service access, the distance-decay effect, poor physical health determinants and access to firearms. Research conducted by the National Centre for Farmer Health between 2004 and 2009 reveals that there is a correlation between obesity and psychological distress among the farming community where suicide rates are recognised as high. Chronic stress overstimulates the regulation of the hypothalamic-pituitary-adrenal (HPA) axis that is associated with abdominal obesity. Increasing physical activity may block negative thoughts, increase social contact, positively influence brain chemistry and improve both physical and mental health. This paper describes the design of the Farming Fit study that aims to identify the effect of physical activity on psychological distress, obesity and health behaviours such as diet patterns and smoking in farm men and women.Methods/Design: For this quasi-experimental (convenience sample) control-intervention study, overweight (Body Mass Index &ge;25 kg/m2) farm men and women will be recruited from Sustainable Farm Families&trade; (SFF) programs held across Victoria, Australia. Baseline demographic data, health data, depression anxiety stress scale (DASS) scores, dietary information, physical activity data, anthropometric data, blood pressure and biochemical analysis of plasma and salivary cortisol levels will be collected. The intervention group will receive an exercise program and regular phone coaching in order to increase their physical activity. Analysis will evaluate the impact of the intervention by longitudinal data (baseline and post intervention) comparison of intervention and control groups.Discussion: This study is designed to examine the effect of physical activity on psychological health and other comorbidities such as obesity, impaired glucose tolerance, hypertension and dyslipidaemia within a high-risk cohort. The outcomes of this research will be relevant to further research and service delivery programs, in particular those tailored to rural communities.<br /

Widening access to medicine: A realist review Journal: Medical Education

While medical school selection research has largely focused on the validity of tools and processes, less attention has been paid to the quality and impact of widening access (WA) pathways. Existing studies are often limited in scope, focusing on single institutions or interventions. This study aimed to develop transferable insights into WA selection practices through a realist evaluation across four Australian medical schools.MethodsBuilding on a prior realist review, we employed the RAMSES II protocol to explore how contextual factors and mechanisms interact to influence WA outcomes through case studies at four medical schools. Data collection included institutional document and website reviews, semi-structured interviews and focus groups with 41 staff and 17 first-year students. The evaluation framework examined Context (diversity within sociocultural settings), Interventions (targeted pathways, adjusted selection scores), Mechanisms (institutional, dispositional, situational), and Outcomes (applicant diversity, selection success).ResultsTwo key interventions were identified as successful across all sites: (1) targeted pathways with selection score adjustments for under-represented groups (e.g., Indigenous, rural, low socio-economic backgrounds), and (2) sustained partnerships with these communities to raise awareness of medicine as a viable career. These partnerships aimed to enhance applicants’ dispositions and readiness for selection.DiscussionThe resulting programme theory identified five main mechanisms underpinning effective WA: visionary leadership, Indigenous cultural safety, longitudinal relational engagement, tailored applicant support, and preparation for selection processes. While demographic shifts, particularly in rural and Indigenous representation, were observed over a 12-year period, the scope of WA remains narrow. Structural changes within institutions pose significant risks to the sustainability of these efforts. ConclusionWe argue for a national, coordinated approach to WA in medical education, underpinned by long-term investment, robust evaluation, and a broader conceptualisation of equity in access. WA must be embedded as a core institutional commitment rather than a peripheral initiative. <br/

Widening access to medicine: A realist review

The under-participation of students from disadvantaged population groups in medical education reflects broader complex structural and societal issues, highlighting that widening access (WA) selection pathways into medicine are highly context dependent. While much literature on WA pathways exists, to date this is limited to small, mostly descriptive, single-site studies; hence there is a need for more robust and theory-driven approaches to yield transferable findings. This realist review sought to develop explanatory theory on designing and implementing selection pathways that successfully widen access to medicine and increase cohort diversity.A realist approach to evidence synthesis identified the mechanisms (M) of action underpinning WA interventions for selection into medical school. We examined how these mechanisms triggered outcomes (O) related to increasing cohort diversity within different contexts (C). Our research design was informed by Pawson’s five iterative strategies for realist review: (1) locate existing theories, (2) search for evidence, (3) select articles, (4) extract and organise data and (5) synthesise the evidence and draw conclusions.Of the 6300 studies identified and screened in the main search, 32 met the inclusion criteria. Five types of WA interventions were reported across the 32 papers:(1) Minimising Bias(2) Modifying selection criteria(3) Collaborating with community(4) Preparing applicants for selection and studying medicine(5) Combining College with Medical SchoolOur realist analysis developed and refined 19 context-intervention-mechanism-outcome (CIMO) configurations. Mechanisms were categorised as addressing institutional, situational, or dispositional barriers to selection into medicine. While situational factors were often the impetus for implementing a WA intervention, the interventions themselves were developed with either an institutional or dispositional focus.There are several known situational barriers that influence the decision of individuals from under-represented minority groups just to apply to medical school. The reviewed studies reported on interventions that demonstrated positive gains in increasing applicants, offers and matriculants in several under-represented populations. More research is needed around mitigating barriers earlier in the journey to medical school (pre-application) through to supportive interventions provided once accepted (post-admission, retention, and graduation) to fully diversify the health workforce.This review highlights how institutions all use demographic characteristics to identify under-represented students, but these demographics are usually blunt one-dimensional measures of disadvantage and therefore limited. This review highlights how sociocultural conditions and policy, either external or within an institution, will drive the commitment and resources made available for a WA intervention. Based on the findings of the review reported here, the review team were left wondering if the interventions being applied are genuinely widening access for disadvantaged applicants to medical education

Male Circumcision and HIV Prevention: Looking to the Future

Now that male circumcision has been shown to have a protective effect for men against HIV infection when engaging in vaginal intercourse with HIV-infected women, the research focus needs to shift towards the operational studies that can pave the way for effective implementation of circumcision programs. Behavioral research is needed to find out how people perceive the procedure and the barriers to and facilitators of uptake. It should also assess the risk of an increase in unsafe sex after circumcision. Social research must examine cultural perceptions of the practice, in Africa and beyond, including how likely uncircumcised communities are to access surgery and what messages are needed to persuade them. Advocates of male circumcision would benefit from research on how to influence health policy-makers, how best to communicate the benefits to the public, and how to design effective delivery models

Farming fit? Dispelling the Australian agrarian myth

Background: Rural Australians face a higher mental health and lifestyle disease burden (obesity, diabetes andcardiovascular disease) than their urban counterparts. Our ongoing research reveals that the Australian farmingcommunity has even poorer physical and mental health outcomes than rural averages. In particular, farm men andwomen have high rates of overweightness, obesity, abdominal adiposity, high blood pressure and psychologicaldistress when compared against Australian averages. Within our farming cohort we observed a significantassociation between psychological distress and obesity, abdominal adiposity and body fat percentage in thefarming population.Presentation of hypothesis: This paper presents a hypothesis based on preliminary data obtained from anongoing study that could potentially explain the complex correlation between obesity, psychological distress andphysical activity among a farming population. We posit that spasmodic physical activity, changing farm practicesand climate variability induce prolonged stress in farmers. This increases systemic cortisol that, in turn, promotesabdominal adiposity and weight gain.Testing the hypothesis: The hypothesis will be tested by anthropometric, biochemical and psychological analysismatched against systemic cortisol levels and the physical activity of the subjects.Implications of the hypothesis tested: Previous studies indicate that farming populations have elevated rates ofpsychological distress and high rates of suicide. Australian farmers have recently experienced challenging climaticconditions including prolonged drought, floods and cyclones. Through our interactions and through the media it isnot uncommon for farmers to describe the effect of this long-term stress with feelings of &lsquo;defeat&rsquo;. By gaining agreater understanding of the role cortisol and physical activity have on mental and physical health we maypositively impact the current rates of psychological distress in farmers.<br /

Topical Oestrogen Keratinises The Human Foreskin and May Help Prevent HIV Infection

With the growing incidence of HIV, there is a desperate need to develop simple, cheap and effective new ways of preventing HIV infection. Male circumcision reduces the risk of infection by about 60%, probably because of the removal of the Langerhans cells which are abundant in the inner foreskin and are the primary route by which HIV enters the penis. Langerhans cells form a vital part of the body's natural defence against HIV and only cause infection when they are exposed to high levels of HIV virions. Rather than removing this natural defence mechanism by circumcision, it may be better to enhance it by thickening the layer of keratin overlying the Langerhans cells, thereby reducing the viral load to which they are exposed. We have investigated the ability of topically administered oestrogen to induce keratinization of the epithelium of the inner foreskin. Histochemically, the whole of the foreskin is richly supplied with oestrogen receptors. The epithelium of the inner foreskin, like the vagina, responds within 24 hours to the topical administration of oestriol by keratinization, and the response persists for at least 5 days after the cessation of the treatment. Oestriol, a cheap, readily available natural oestrogen metabolite, rapidly keratinizes the inner foreskin, the site of HIV entry into the penis. This thickening of the overlying protective layer of keratin should reduce the exposure of the underlying Langerhans cells to HIV virions. This simple treatment could become an adjunct or alternative to surgical circumcision for reducing the incidence of HIV infection in men

Male Circumcision for Prevention of HIV Transmission: What the New Data Mean for HIV Prevention in the United States

Recent clinical trials in Africa found that male circumcision reduces the risk of acquiring HIV from heterosexual sex--what are the implications of these studies for the United States