Ammonia toxicity to the brain: effects on creatine metabolism and transport and protective roles of creatine.

Hyperammonemia can provoke irreversible damage to the developing brain, with the formation of cortical atrophy, ventricular enlargement, demyelination or gray and white matter hypodensities. Among the various pathogenic mechanisms involved, alterations in cerebral energy have been demonstrated. In particular, we could show that ammonia exposure generates a secondary deficiency in creatine in brain cells, by altering the brain expression and activity of the genes allowing creatine synthesis (AGAT and GAMT) and transport (SLC6A8). On the other hand, it is known that creatine administration can exert protective effects in various neurodegenerative processes. We could also show that creatine co-treatment under ammonia exposure can protect developing brain cells from some of the deleterious effects of ammonia, in particular axonal growth impairment. This article focuses on the effects of ammonia exposure on creatine metabolism and transport in developing brain cells, and on the potential neuroprotective properties of creatine in the brain exposed to ammonium.

Geographic variation in sex-chromosome differentiation in the common frog (Rana temporaria).

In sharp contrast with birds and mammals, sex-determination systems in ectothermic vertebrates are often highly dynamic and sometimes multifactorial. Both environmental and genetic effects have been documented in common frogs (Rana temporaria). One genetic linkage group, mapping to the largest pair of chromosomes and harbouring the candidate sex-determining gene Dmrt1, associates with sex in several populations throughout Europe, but association varies both within and among populations. Here, we show that sex association at this linkage group differs among populations along a 1500-km transect across Sweden. Genetic differentiation between sexes is strongest (FST  = 0.152) in a northern-boreal population, where male-specific alleles and heterozygote excesses (FIS  = -0.418 in males, +0.025 in females) testify to a male-heterogametic system and lack of X-Y recombination. In the southernmost population (nemoral climate), in contrast, sexes share the same alleles at the same frequencies (FST  = 0.007 between sexes), suggesting unrestricted recombination. Other populations show intermediate levels of sex differentiation, with males falling in two categories: some cluster with females, while others display male-specific Y haplotypes. This polymorphism may result from differences between populations in the patterns of X-Y recombination, co-option of an alternative sex-chromosome pair, or a mixed sex-determination system where maleness is controlled either by genes or by environment depending on populations or families. We propose approaches to test among these alternative models, to disentangle the effects of climate and phylogeography on the latitudinal trend, and to sort out how this polymorphism relates to the 'sexual races' described in common frogs in the 1930s.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population (epublish)

BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. METHODS: We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS: The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Sex chromosomes and male functions: where do new genes go?

The position of a gene in the genome may have important consequences for its function. Therefore, when a new duplicate gene arises, its location may be critical in determining its fate. Our recent work in humans, mouse, and Drosophila provided a test by studying the patterns of duplication in sex chromosome evolution. We revealed a bias in the generation and recruitment of new gene copies involving the X chromosome that has been shaped largely by selection for male germline functions. The gene movement patterns we observed reflect an ongoing process as some of the new genes are very young while others were present before the divergence of humans and mouse. This suggests a continuing redistribution of male-related genes to achieve a more efficient allocation of male functions. This notion should be further tested in organisms employing other sex determination systems or in organisms differing in germline sex chromosome inactivation. It is likely that the selective forces that were detected in these studies are also acting on other types of duplicate genes. As a result, future work elucidating sex chromosome differentiation by other mutational mechanisms will shed light on this important process.

Sex differences: From mental rotation to object location memory, an ERP study

Sex differences in cognition have been largely investigated. The most consistent sex differences favoring females are observed in object location memory involving the left hemisphere whereas the most consistent sex differences favoring males are observed in tasks that require mental rotation involving the right hemisphere. Here we used a task involving these two abilities to see the impact of mental rotation on object location memory. To that end we used a combination of behavioral and event-related potential (ERP) electroencephalography (EEG) measures.A computer screen displayed a square frame of 4 pairs of images (a "teddy" bear, a shoe, an umbrella and a lamp) randomly arranged around a central fixation cross. After a 10-second interval for memorization, images disappeared and were replaced by a test frame with no image but a random pair of two locations marked in black. In addition, this test frame was randomly displayed either in the original orientation (0° rotation) or in the rotated one (90° clockwise - CW - or 90° counterclockwise - CCW). Preceding the test frame, an arrow indicating the presence or the absence of rotation of the frame was displayed on the screen. The task of the participants (15 females and 15 males) was to determine if two marked locations corresponded or not to a pair of identical images. Each response was followed by feedback.Findings showed no significant sex differences in the performance of the original orientation. In comparison with this position, the rotation of the frame produced an equal decrease of male and female performance. In addition, this decrease was significantly higher when the rotation of the frame was in a CCW direction. We further assessed the ERP when the arrow indicated the direction of rotation as stimulus-onset, during four time windows representing major components C1, P1, N1 and N2. Although no sex differences were observed in performance, brain activities differed according to sex. Enhanced amplitudes were found for the CCW compared to CW rotation over the right posterior areas for the P1, N1 and N2 components for men as well as for women. Major topographical differences related to sex were measured for the CW rotation condition as marked lateralized amplitude: left-hemisphere amplitude larger than right one was measured during P1 time range for men. These similar patterns prolonged from P1 to N1 for women. Early distinctions were found in interaction with sex between CCW and CW waveform amplitudes, expressing over anterior electrode sites during C1 time range (0-50 ms post-stimulus).In conclusion (i) women do not outperform men in object location memory in this study (absence of rotation condition); (ii) mental rotation, in particular the direction of rotation, influences performance on object location memory; (iii) CCW rotation is associated with activity in the right parietal hemisphere whereas the CW rotation involves the left parietal hemisphere; (iv) this last effect is less pronounced in males, which could explain why greater involvement of right parietal areas in men and of bilateral posterior areas in women is generally reported in mental rotation tasks; and (v) the early distinctions between both directions of rotation located over anterior sites could be related to sex differences in their respective involvement of control mechanisms.

Unwanted sexual experiences among adolescents: shedding light on the gray zone between consensual and non-consensual sex.

This study aimed at exploring adolescents' perceptions of unwanted sexual experiences (USE) in order to set up definitions, categories, and boundaries on the continuum between consensual and non-consensual sex. METHODS: We conducted a qualitative thematic analysis of four focus group discussions gathering a total of 29 male and female adolescents aged 16-20 years. RESULTS: Analysis of participants' discourse revealed three main characteristics that define USE, namely, regret, as most situations discussed were said to be acceptable or not in terms of whether there were regrets after the fact; misperception of sexual intent; and lack of communication between partners. CONCLUSIONS: Our findings revealed that health professionals should be aware of the subtle aspects identifying USE when screening for situations that can have adverse psychological consequences. Where prevention is concerned, it appears important to address these aspects of USE in sex education classes.

Inverse association between circulating vitamin D and mortality-dependent on sex and cause of death?

BACKGROUND AND AIMS: In various populations, vitamin D deficiency is associated with chronic diseases and mortality. We examined the association between concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and all-cause as well as cause-specific mortality. METHODS AND RESULTS: The study included 3404 participants of the general adult Swiss population, who were recruited between November 1988 and June 1989 and followed-up until the end of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox proportional hazards regression was used to examine the association between 25(OH)D concentration and all-cause and cause-specific mortality adjusting for sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10 ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D concentration was inversely associated with cancer mortality in men (HR = 0.72, 95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93-1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality association. CONCLUSION: 25(OH)D was similarly inversely related to all-cause mortality in men and women. However, we observed opposite effects in women and men with respect to cardiovascular and cancer mortality.

Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report.

BACKGROUND: Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. METHOD: This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. RESULT: We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. CONCLUSION: This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.

Risk reduction practices in men who have sex with men in Switzerland: serosorting, strategic positioning, and withdrawal before ejaculation.

The aim of this study was to identify predictors of intentional use of the HIV risk reduction practices of serosorting, strategic positioning, and withdrawal before ejaculation during unprotected anal intercourse (UAI) with casual partners. A cross-sectional survey pertaining to the Swiss HIV behavioral surveillance system, using an anonymous self-administered questionnaire, was conducted in 2007 in a self-selected sample of men having sex with other men (MSM). Analysis was restricted to participants with UAI with casual partner(s) (N = 410). Logistic regression was used to estimate factors associated with intentional use of serosorting, strategic positioning, and withdrawal before ejaculation. In the previous 12 months, 71% of participants reported having UAI with a casual partner of different or unknown HIV-status. Of these, 47% reported practicing withdrawal, 38% serosorting, and 25% strategic positioning. In the 319 participants with known HIV-status, serosorting was associated with frequent Internet use to find partners (OR = 2.32), STI (OR = 2.07), and HIV testing in the past 12 months (OR = 1.81). Strategic positioning was associated with HIV-status (OR = 0.13) and having UAI with a partner of different or unknown HIV-status (OR = 3.57). Withdrawal was more frequently practiced by HIV-negative participants or participants reporting high numbers of sexual partners (OR = 2.48) and having UAI with a partner of unknown or different serostatus (OR = 2.08). Risk reduction practices are widely used by MSM, each practice having its own specificities. Further research is needed to determine the contextual factors surrounding harm reduction practices, particularly the strategic or opportunistic nature of their use.

Sex differences in the neurobiology of fear conditioning and extinction: a preliminary fMRI study of shared sex differences with stress-arousal circuitry.

BACKGROUND: The amygdala, hippocampus, medial prefrontal cortex (mPFC) and brain-stem subregions are implicated in fear conditioning and extinction, and are brain regions known to be sexually dimorphic. We used functional magnetic resonance imaging (fMRI) to investigate sex differences in brain activity in these regions during fear conditioning and extinction. METHODS: Subjects were 12 healthy men comparable to 12 healthy women who underwent a 2-day experiment in a 3 T MR scanner. Fear conditioning and extinction learning occurred on day 1 and extinction recall occurred on day 2. The conditioned stimuli were visual cues and the unconditioned stimulus was a mild electric shock. Skin conductance responses (SCR) were recorded throughout the experiment as an index of the conditioned response. fMRI data (blood-oxygen-level-dependent [BOLD] signal changes) were analyzed using SPM8. RESULTS: Findings showed no significant sex differences in SCR during any experimental phases. However, during fear conditioning, there were significantly greater BOLD-signal changes in the right amygdala, right rostral anterior cingulate (rACC) and dorsal anterior cingulate cortex (dACC) in women compared with men. In contrast, men showed significantly greater signal changes in bilateral rACC during extinction recall. CONCLUSIONS: These results indicate sex differences in brain activation within the fear circuitry of healthy subjects despite similar peripheral autonomic responses. Furthermore, we found that regions where sex differences were previously reported in response to stress, also exhibited sex differences during fear conditioning and extinction.

Host sex and ectoparasites choice: preference for, and higher survival on female hosts.

1. Sex differences in levels of parasite infection are a common rule in a wide range of mammals, with males usually more susceptible than females. Sex-specific exposure to parasites, e.g. mediated through distinct modes of social aggregation between and within genders, as well as negative relationships between androgen levels and immune defences are thought to play a major role in this pattern. 2. Reproductive female bats live in close association within clusters at maternity roosts, whereas nonbreeding females and males generally occupy solitary roosts. Bats represent therefore an ideal model to study the consequences of sex-specific social and spatial aggregation on parasites' infection strategies. 3. We first compared prevalence and parasite intensities in a host-parasite system comprising closely related species of ectoparasitic mites (Spinturnix spp.) and their hosts, five European bat species. We then compared the level of parasitism between juvenile males and females in mixed colonies of greater and lesser mouse-eared bats Myotis myotis and M. blythii. Prevalence was higher in adult females than in adult males stemming from colonial aggregations in all five studied species. Parasite intensity was significantly higher in females in three of the five species studied. No difference in prevalence and mite numbers was found between male and female juveniles in colonial roosts. 4. To assess whether observed sex-biased parasitism results from differences in host exposure only, or, alternatively, from an active, selected choice made by the parasite, we performed lab experiments on short-term preferences and long-term survival of parasites on male and female Myotis daubentoni. When confronted with adult males and females, parasites preferentially selected female hosts, whereas no choice differences were observed between adult females and subadult males. Finally, we found significantly higher parasite survival on adult females compared with adult males. 5. Our study shows that social and spatial aggregation favours sex-biased parasitism that could be a mere consequence of an active and adaptive parasite choice for the more profitable host.

Resurgence of HIV infection among men who have sex with men in Switzerland: mathematical modelling study.

BACKGROUND: New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. METHODOLOGY/PRINCIPAL FINDINGS: The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. CONCLUSIONS/SIGNIFICANCE: The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.