Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men

Drug concentrations associated with protection from HIV-1 acquisition have not been determined. We evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial (1). In this randomized placebo-controlled trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was detected less frequently in blood plasma and in viable cryopreserved peripheral blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%; P < 0.001). An intracellular concentration of the active form of tenofovir, tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that, when analyzed according to the iPrEx model, corresponded to an HIV-1 risk reduction of 76% for two doses per week, 96% for four doses per week, and 99% for seven doses per week. Pro-phylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.

Frequency of subtype B and F1 dual infection in HIV-1 positive, Brazilian men who have sex with men

Background: Because various HIV vaccination studies are in progress, it is important to understand how often inter- and intra-subtype co/superinfection occurs in different HIV-infected high-risk groups. This knowledge would aid in the development of future prevention programs. In this cross-sectional study, we report the frequency of subtype B and F1 co-infection in a clinical group of 41 recently HIV-1 infected men who have sex with men (MSM) in Sao Paulo, Brazil. Methodology: Proviral HIV-1 DNA was isolated from subject's peripheral blood polymorphonuclear leukocytes that were obtained at the time of enrollment. Each subject was known to be infected with a subtype B virus as determined in a previous study. A small fragment of the integrase gene (nucleotide 4255-4478 of HXB2) was amplified by nested polymerase chain reaction (PCR) using subclade F1 specific primers. The PCR results were further confirmed by phylogenetic analysis. Viral load (VL) data were extrapolated from the medical records of each patient. Results: For the 41 samples from MSM who were recently infected with subtype B virus, it was possible to detect subclade F1 proviral DNA in five patients, which represents a co-infection rate of 12.2%. In subjects with dual infection, the median VL was 5.3 x 10(4) copies/ML, whereas in MSM that were infected with only subtype B virus the median VL was 3.8 x 10(4) copies/ML (p > 0.8). Conclusions: This study indicated that subtype B and F1 co-infection occurs frequently within the HIV-positive MSM population as suggested by large number of BF1 recombinant viruses reported in Brazil. This finding will help us track the epidemic and provide support for the development of immunization strategies against the HIV.

The contrasting role of heterochromatin in the differentiation of sex chromosomes: an overview from Neotropical fishes

During the evolutionary process of the sex chromosomes, a general principle that arises is that cessation or a partial restriction of recombination between the sex chromosome pair is necessary. Data from phylogenetically distinct organisms reveal that this phenomenon is frequently associated with the accumulation of heterochromatin in the sex chromosomes. Fish species emerge as excellent models to study this phenomenon because they have much younger sex chromosomes compared to higher vertebrates and many other organisms making it possible to follow their steps of differentiation. In several Neotropical fish species, the heterochromatinization, accompanied by amplification of tandem repeats, represents an important step in the morphological differentiation of simple sex chromosome systems, especially in the ZZ/ZW sex systems. In contrast, multiple sex chromosome systems have no additional increase of heterochromatin in the chromosomes. Thus, the initial stage of differentiation of the multiple sex chromosome systems seems to be associated with proper chromosomal rearrangements, whereas the simple sex chromosome systems have an accumulation of heterochromatin. In this review, attention has been drawn to this contrasting role of heterochromatin in the differentiation of simple and multiple sex chromosomes of Neotropical fishes, highlighting their surprising evolutionary dynamism.

The vulnerable male, or the sex ratio among fetal deaths in Brazil

Some studies indicate the existence of innate male vulnerabilities, especially during the perinatal period. The current study is a cross-sectional analysis of fetal mortality in Brazil according to sex from 2000 to 2009, stratified by maternal characteristics (age, schooling, and gestational age), using Ministry of Health data (DATASUS). The analysis included all fetal deaths from 2000 to 2009, except when the sex of the fetus was not recorded. The male/female sex ratio (SR) for all fetal deaths was 1.188. Analysis of maternal characteristics showed that the SR was statistically higher (p < 0.01) in mothers that were younger (10-14 years), had no formal schooling, and with gestational age < 22 weeks. The study showed a statistically higher-than-expected SR (p < 0.01) for 13 underlying causes of death and a lower SR for two others. The results suggest a potential innate male vulnerability.

STIM 1/Orai 1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats

Sex differences in Ca2+-dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca2+ entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca2+ mobilization due to diminished activation of Orai 1/STIM 1 (stromal interaction molecule I). In addition, we investigated whether ovariectomy in females affects the activation of the Orai 1/STIM 1 pathway. Endothelium-denuded aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive rats) and WKY (Wistar Kyoto) rats and from OVX (ovariectomized) or sham female SHRSP and WKY rats were used to functionally evaluate Ca2+ influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca2+-loading period; (ii) similar transient contraction during Ca2+ release from the intracellular stores; (iii) increased activation of STIM 1 and Orai1, as shown by the blockade of STIM 1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca2+-loading period; and (iv) increased expression of STIM I and Orai I. Additionally, we found that aortas from OVX-SHRSP showed increased contraction during the Ca2+-loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM I expression. These findings suggest that augmented activation of STIM 1/Orai 1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca2+ levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai 1 pathway, contributing to vascular protection observed in female rats.

The methylation patterns of the IGF2 and IGF2R genes in bovine spermatozoa are not affected by flow-cytometric sex sorting

The objectives of this study were to investigate the effect of sexing by flow cytometry on the methylation patterns of the IGF2 and IGF2R genes. Frozen-thawed, unsorted, and sex-sorted sperm samples from four Nellore bulls were used. Each ejaculate was separated into three fractions: non-sexed (NS), sexed for X-sperm (SX), and sexed for Y-sperm (SY). Sperm were isolated from the extender, cryoprotectant, and other cell types by centrifugation on a 40:70% Percoll gradient, and sperm pellets were used for genomic DNA isolation. DNA was used for analyses of the methylation patterns by bisulfite sequencing. Methylation status of the IGF2 and IGF2R genes were evaluated by sequencing 195 and 147 individual clones, respectively. No global differences in DNA methylation were found between NS, SX, and SY groups for the IGF2 (P=0.09) or IGF2R genes (P=0.38). Very specific methylation patterns were observed in the 25th and 26th CpG sites in the IGF2R gene. representing higher methylation in NS than in the SX and SY groups compared with the other CpG sites. Further, individual variation in methylation patterns was found among bulls. In conclusion, the sex-sorting procedure by flow cytometry did not affect the overall DNA methylation patterns of the IGF2 and IGF2R genes, although individual variation in their methylation patterns among bulls was observed. Mol. Reprod. Dev. 79:7784, 2012. (C) 2011 Wiley Periodicals, Inc.

Household income, sex and respiratory mortality in Sao Paulo, Brazil, 1996-2010

SETTING: Respiratory mortality rates are declining in several countries, including Brazil; however, the effect of socio-economic indicators and sex is unclear. OBJECTIVE: To identify differences in mortality trends according to income and sex in the city of Sao Paulo, Brazil. DESIGN: We performed a time-trend analysis of all respiratory diseases, including chronic obstructive pulmonary disease (COPD), lung cancer and tuberculosis, using Joinpoint regression comparing high, middle and low household income levels from 1996 to 2010. RESULTS: The annual per cent change (APC) and 95% confidence intervals (95%CIs) for death rates from all respiratory disease in men in high-income areas was -1.1 (95%CI -2.7 to 0.5) in 1996-2002 and -4.3 (95%CI -5.9 to -2.8) in 2003-2009. In middle- and low-income areas, the decline was respectively -1.5 (95%CI -2.2 to -0.7) and -1.4 (95%CI -1.9 to -0.8). For women, the APC declined in high-income (-1.0, 95%CI -1.9 to -0.2) and low-income areas (0.8, 95%CI -1.3 to -0.2), but not in middle-income areas (-0.5, 95%CI -1.4 to 0.3) from 1996 to 2010. CONCLUSION: Death rates due to COPD and all respiratory disease declined more consistently in men from high-income areas. Mortality due to lung cancer decreased in men, but increased in women in middle- and low-income areas.

Cuticular Hydrocarbon Variation of Castes and Sex in the Weaver Ant Camponotus textor (Hymenoptera: Formicidae)

Cuticular hydrocarbons play important roles as chemical signatures of individuals, castes, sex and brood. They also can mediate the regulation of egg laying in ants, by informing directly or indirectly the reproductive status of queens. In this study we asked whether cuticular hydrocarbon profiles are correlated with castes and sex of Camponotus textor. Cuticular hydrocarbons were extracted from part of a mature colony (80 workers, 27 major workers, 27 queens, 27 virgin queens and 27 males). Results showed that cuticular hydrocarbons varied quantitatively and qualitatively among the groups and this variation was sufficiently strong to allow separation of castes and genders. We discuss the specificity of some compounds as possible regulatory compounds of worker tasks and reproduction in C. textor.

Women's Poorer Satisfaction With Their Sex Lives Following Gynecologic Cancer Treatment

Gynecologic cancer treatment can lead to anatomical changes in the genitalia that may impair sexual response. As a result, the authors aimed to assess women's self-perceptions of their sex lives following gynecologic cancer treatment and the impact of such treatment on sexual function. Thirty sexually active women were examined. At the first meeting with a physician sex therapist, women were asked about their satisfaction with their sexual activities prior to and after gynecologic cancer treatment, either with a partner or alone, and how many times per month they had sexual intercourse prior to the cancer diagnosis and after treatment. Women reported significantly worse sex lives and a significantly lower frequency of sexual relations following cancer treatment. All participants reported pain on vaginal penetration and feeling uncomfortable in discussing their sexual difficulties with the oncologist. The findings show that women experienced impaired sexual function, as well as poorer quality of sexual function, following gynecologic cancer treatment. Nurses should provide basic guidelines about sexual function to all patients who undergo treatment for gynecologic cancer.

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Abstract Background Melatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation. Methods Twenty-four adult Wistar rats, 60 days old (+/- 250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [100 μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m. Results Melatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated. Conclusions We suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.

Pain in preterm infants: effects of sex, gestational age, and neonatal illness severity

Neonates hospitalized in a neonatal intensive care unit are exposed to many painful and stressful procedures. Biobehavioral pain reactivity in preterm infants during the neonatal period may reflect the capacity of the central nervous system to regulate arousal and neurobiological organization. We review empirical studies on the effects of sex, gestational age, and neonatal illness severity on pain reactivity in children born preterm. A literature search was conducted using PubMed, Institute of Scientific Information Web of Science, PsycINFO, Latin American and Caribbean Health Sciences Literature, and Scientific Electronic Library Online databases. Additionally, a special search was performed in online journals that publish pain studies including Pain, Early Human Development, European Journal of Pain, and Pain Management Nursing. The literature search covered the period from 2004 to 2009. Data were extracted according to predefined inclusion and exclusion criteria. Of the 18 studies reviewed, 16 analyzed gestational age, 13 examined neonatal illness severity, and eight focused on sex. Most of the studies analyzed more than one of these three variables. The majority of the studies found effects of gestational age (n = 14) and neonatal illness severity (n = 11) on pain responses. Only two studies found an influence of sex on infant pain responses. In conclusion, gestational age and neonatal illness severity influence pain responses in infants born preterm. Further studies should be conducted to examine the influence of sex on pain responses.

No evidence of predation causing female-biased sex ratios in marine pelagic copepods

Although sex ratios close to unity are expected in dioecious species, biased sex ratios are common in nature. It is essential to understand causes of skewed sex ratios in situ, as they can lead to mate limitation and have implications for the success of natural populations. Female-skewed sex ratios are commonly observed in copepods in situ. Here we discuss the challenges of copepod sex ratio research and provide a critical review of factors determining copepod sex ratios, focusing on 2 main objectives. The first is a critique of the male predation theory, which is currently the main process thought to be responsible for female-skewed sex ratios. It assumes that males have higher mortality because of increased vulnerability to predation during their search for mates. We show that there is little support for the male predation theory, that sex ratios skewed toward females occur in the absence of predation, that sex ratios are not related to predation pressure, and that where sex-skewed predation does occur, it is biased toward females. Our second objective is to suggest alternative hypotheses regarding the determination of sex ratios. We demonstrate that environmental factors, environmental sex determination and sex change have strong effects on copepod sex ratios, and suggest that differential physiological longevity of males and females may be more important in determining sex ratios than previously thought. We suggest that copepod sex ratios are the result of a mixture of factors.

Female-biased sex ratios in marine pelagic copepods: Response to Hirst et al. (2013)

Hirst et al. (2013; Mar Ecol Prog Ser 489:297-298) suggest that Gusmão et al. (2013; Mar Ecol Prog Ser 482:279-298) misinterpreted the findings of Hirst et al. (2010; Limnol Oceanogr 55:2193-2206). They restate that the major factors determining sex ratio in pelagic copepods act upon the adult stage, but they place less emphasis on the idea that predation on male copepods is a likely determinant, and highlight the role of physiological longevity. Here we reconsider the data and confirm our position that at present there is limited evidence to support the theory of male-skewed predation. However, we agree that sex determination is governed by a combination of factors, with the relative emphasis being the main point of contention between the 2 parties.

Manipulation of the periovulatory sex steroidal milieu affects endometrial but not luteal gene expression in early diestrus Nelore cows

In beef cattle, the ability to conceive has been associated positively with size of the preovulatory follicle (POF). Proestrus estradiol and subsequent progesterone concentrations can regulate the endometrium to affect receptivity and fertility. The aim of the present study was to verify the effect of the size of the POF on luteal and endometrial gene expression during subsequent early diestrus in beef cattle. Eighty-three multiparous, nonlactating, presynchronized Nelore cows received a progesterone-releasing device and estradiol benzoate on Day–10 (D 10). Animals received cloprostenol (large follicle-large CL group; LF-LCL; N ¼ 42) or not (small follicle-small CL group; SF-SCL; N ¼ 41) on D 10. Progesterone devices were withdrawn and cloprostenol administered 42 to 60 hours (LF-LCL) or 30 to 36 hours (SF-SCL) before GnRH treatment (D0). Tissues were collected at slaughter on D7. The LF-LCL group had larger (P < 0.0001) POF (13.24 0.33 mm vs. 10.76 0.29 mm), greater (P < 0.0007) estradiol concentrations on D0 (2.94 0.28 pg/mL vs. 1.27 0.20 pg/mL), and greater (P < 0.01) progesterone concentrations on D7 (3.71 0.25 ng/mL vs. 2.62 0.26 ng/mL) compared with the SF-SCL group. Luteal gene expression of vascular endothelial growth factor A, kinase insert domain receptor, fms-related tyrosine kinase 1, steroidogenic acute regulatory protein, cytochrome P450, family 11, subfamily A, polypeptide 1, and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid deltaisomerase 7 was similar between groups. Endometrial gene expression of oxytocin receptor and peptidase inhibitor 3, skin-derived was reduced, and estrogen receptor alpha 2, aldo-keto reductase family 1, member C4, and lipoprotein lipase expression was increased in LF-LCL versus SF-SCL. Results support the hypothesis that the size of the POF alters the periovulatory endocrine milieu (i.e., proestrus estradiol and diestrus progesterone concentrations) and acts on the uterus to alter endometrial gene expression. It is proposed that the uterine environment and receptivity might also be modulated. Additionally, it is suggested that increased progesterone secretion of cows ovulating larger follicles is likely due to increased CL size rather than increased luteal expression of steroidogenic genes.

Kännbara förändringar : En kvalitativ studie om sex ungdomars upplevelser och tankar kring att erhålla MST

Studiens syfte är att studera hur ungdomar som genomgått Multisystemisk Terapi, MST, upplever denna behandling. Författarna avser således ge en bild av och få en djupare förståelse av deras tankar kring denna behandlingsform. MST är en öppenvårdsbehandling som vänder sig till antisociala ungdomar och deras familjer. Det har visat sig att institutionsplacering av ungdomar många gånger inte leder till önskvärda resultat. Metoden, som grundar sig på systemteori och socialekologiska teorier, utvecklades som ett alternativ till dessa ofta kostsamma placeringar. MST bygger även på kunskaper om vad som orsakar antisocialt beteende hos ungdomar. Studien utfördes genom kvalitativa intervjuer med sex ungdomar som själva genomgått och avslutat MST-behandling. Dessa intervjuer sammanställdes och analyserades utifrån följande teman: Inställning till insatsen, Upplevelse av insatsen och Upplevt resultat. Resultatet visade att ungdomarna upplevde MST på olika sätt, det vill säga både positivt och negativt. Det som förenade ungdomarna var att samtliga tyckte att det var mer eller mindre jobbigt att erhålla MST. Analysen visade bland annat att en fungerande kommunikation under behandlingen, mellan så många delar av nätverket som möjligt, är viktigt för ett lyckat behandlingsresultat och att en fungerande MST-insats minskar riskfaktorerna kring den unge. Slutligen diskuterades de funna resultaten, MST som metod samt vikten av att oberoende forskare genomför, både kvantitativa och kvalitativa, utvärderingar av nya behandlingsmetoder.