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The outbreak of Covid-19 negatively affected mental health and increased loneliness. The subjective feeling of loneliness is influenced by genetic and social factors and has a negative impact on mental health. From March 2020 to June 2021 loneliness was investigated in N = 517 individuals using monthly acquired questionnaire data and Latent Growth Curve Analysis. Associations of social factors and polygenic risk scores (PRSs, n = 361) with class membership were investigated. Three classes ("average", 40%; "not lonely", 38%; "elevated loneliness", 22%) were identified, that differ significantly regarding loneliness, mental dysfunction, and response to the lockdown phases. Individuals with a high PRS for neuroticism are more likely to belong to the "elevated loneliness" class, living with another person is a protective factor. As the "elevated loneliness" class was at the highest risk of mental dysfunction, our findings underscore the importance of identifying those individuals to implement counteractive measures. [ABSTRACT FROM AUTHOR]

Substantial evidence shows that physical activity and fitness play a protective role in the development of stress related disorders. However, the beneficial effects of fitness for resilience to modern life stress are not fully understood. Potentially protective effects may be attributed to enhanced resilience via underlying psychosocial mechanisms such as self-efficacy expectations. This study investigated whether physical activity and fitness contribute to prospectively measured resilience and examined the mediating effect of general self-efficacy. 431 initially healthy adults participated in fitness assessments as part of a longitudinal-prospective study, designed to identify mechanisms of resilience. Self-efficacy and habitual activity were assessed in parallel to cardiorespiratory and muscular fitness, which were determined by a submaximal step-test, hand strength and standing long jump test. Resilience was indexed by stressor reactivity: mental health problems in relation to reported life events and daily hassles, monitored quarterly for nine months. Hierarchical linear regression models and bootstrapped mediation analyses were applied. We could show that muscular and self-perceived fitness were positively associated with stress resilience. Extending this finding, the muscular fitness–resilience relationship was partly mediated by self-efficacy expectations. In this context, self-efficacy expectations may act as one underlying psychological mechanism, with complementary benefits for the promotion of mental health. While physical activity and cardiorespiratory fitness did not predict resilience prospectively, we found muscular and self-perceived fitness to be significant prognostic parameters for stress resilience. Although there is still more need to identify specific fitness parameters in light of stress resilience, our study underscores the general relevance of fitness for stress-related disorders prevention. [ABSTRACT FROM AUTHOR]

The endocannabinoid system is important for skin homeostasis and alterations are linked to inflammatory diseases like atopic dermatitis (AD). Importantly, activation of cannabinoid receptor CB2 decreases pruritus and inflammation in mouse models. Reduction of inactivation of endogenous cannabinoids could, therefore, be a therapeutic option for AD. Dogs spontaneously develop AD, which closely mimics the human disease making them suitable to test new therapies. Our study aimed to test the effects of a topical endocannabinoid membrane transporter inhibitor (WOL067-531, 1% gel) on pruritus and dermatitis in a canine model of AD. Nineteen Beagles allergic to dust mites (DM) were randomized to receive either active ingredient or vehicle on inguinal area while challenged epicutaneously with DM twice weekly for 28 days. Treatment was administered twice daily and started after three challenges (day 8). Dermatitis and pruritus were scored weekly by personnel blinded to treatment allocation. Dermatitis was scored using a validated scoring system and pruritus was scored using camera recordings. After a 4-week washout, dogs were crossed over and the study was repeated. On days 15 and 22, dermatitis scores were significantly increased after DM challenge in the vehicle group (16.34, p = 0.0089 and 7.42, p = 0.04845, respectively) but not in the active ingredient group (p = 0.3177 and p = 0.3190, respectively). Significant decrease on pruritus both on inguinal area and overall (p = 0.048 and p = 0.032, respectively) occurred in the active ingredient group. No adverse effects were noted. In conclusion, the newly developed topical endocannabinoid membrane transporter inhibitor (WOL067-531) minimized allergic flares and pruritus in a canine model of AD. [ABSTRACT FROM AUTHOR]

Cohort studies are often enriched for a primary exposure of interest to improve cost-effectiveness, which presents analytical challenges not commonly discussed in epidemiology. In this paper, we use causal diagrams to represent exposure-enriched cohort studies, illustrate a scenario wherein the risk ratio for the effect of a secondary exposure on an outcome is biased, and propose an analytical method for correcting for such bias. In our motivating example, maternal smoking (Z) is a cause of fetal growth restriction (X), which subsequently affects preterm birth (Y) (i.e., Z → X → Y); strong positive associations exist between both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to 50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in the risk ratio for the total effect of Z on Y. After application of inverse probability weights, the bias is corrected, with a small loss of efficiency in comparison with a same-sized study without X-enrichment. With increasing interest in conducting secondary analyses to reduce research costs, caution should be employed when analyzing studies that have already been enriched, intentionally or unintentionally, for a primary exposure of interest. Causal diagrams can help identify scenarios in which secondary analyses may be biased. Inverse probability weights can be used to remove the bias. [ABSTRACT FROM AUTHOR]

This paper proves that the ratios of consecutive terms of the m-bonacci sequence converge to a limit φm < 2 and, as m → ∞, these φm converge to 2. Further, it is shown that the generating functions for the m-bonacci sequences converge pointwise to the geometric series. [ABSTRACT FROM AUTHOR]

Information on the pathophysiology of glucocorticoid-induced osteoporosis (010) is limited, since its clinical picture often reflects a combined effect of glucocorticoids (GC) and the treated systemic disease (i.e., inflammation and immobility). In 50 healthy adult (30-mo-old) primiparous Göttingen minipigs, we studied the short-term (8 mo, n = 30) and long-term (15 mo, n = 10) effect of GC on bone and mineral metabolism longitudinally and cross-sectionally compared with a control group (n = 10). All animals on GC treatment received prednisolone orally at a dose of 1.0 mg·kg body wt-1·day-1 for 8 wk and thereafter at 0.5 mg/kg body wt day-1. In the short term, GC reduced bone mineral density (BMD) at the lumbar spine by -47.5 ± 5.1 mg/cm³ from baseline (P < 0.001), which was greater (P < 0.05) than the loss [not significant (NS)] in the control group of -11.8 ± 12.6 mg/cm³. Calcium absorption decreased from baseline by -2,488 ± 688 mg/7 days (P < 0.001) compared with -1,380 ± 1,297 mg/7 days (NS) in the control group. Plasma bone alkaline phosphatase (BAP) decreased from baseline by -17.8 ± 2.2 U/l (P < 0.000), which was significantly different (P < 0.05) from the value of the control group of -1.43 ± 4.8 U/l. In the long term, the loss of BMD became more pronounced and bone mineral content (BMC), trabecular thickness, mechanical stability, calcium absorption, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and parathyroid hormone tended to be lower compared with the control group. There was a negative association between the cumulative dose of GC and BMD, which was associated with impaired osteoblastogenesis. In conclusion, the main outcomes after GC treatment are comparable to symptoms of GC-induced osteoporosis in human subjects. Thus the adult Göttingen miniature pig appears to be a valuable animal model for GC-induced osteoporosis. [ABSTRACT FROM AUTHOR]

Long term tolerance of cardiac allografts has been achieved in non-human primates (NHPs) using a mixed chimerism protocol and by co-transplanting a kidney from the same heart and bone marrow donor. In stark contrast, heart alone recipients rejected in 150-180 days. T cell subset analyses showed a greater expansion of regulatory T cells (Treg) in heart/kidney recipients compared to heart alone controls. To achieve tolerance of isolated heart allografts, we added IL-2 and/or anti-IL6R therapy to enhance host Treg activity. Twelve cynomolgus heart alone transplant recipients underwent donor bone marrow transplantation with mixed chimerism conditioning that included non-myeloablative total body irradiation, thymic irradiation, horse anti-thymocyte globulin, anti-CD154 mAb, and cyclosporine until POD 28. Five animals in Group A received low dose IL-2 (1MIU/m2 SC from POD -6 to 5) and IL-6 receptor blockade with tocilizumab (10 mg/kg IV on POD 0, 7, 14, 21, 28, 56, 84, and 112). Seven recipients in Group B, received tocilizumab alone (10 mg/kg IV on POD 0, 7, 14, 21, 28, 56, and 84). In Group A, 3/5 animals rejected their allografts at days 127, 198, and 254 post-transplant with evidence of acute cellular rejection (ACR), antibody mediated rejection (AMR), and donor specific antibodies (DSA). Two animals died on days 7 and 11 post-transplant from sepsis and pancytopenia, respectively. In Group B, 3/7 recipients are ongoing (POD 111 and 62) with one animal over 509 days with no evidence of ACR. 1/7 rejected at day 169 post-transplant with ACR 3R, pAMR3, and DSA and 3/7 animals died on days 5, 9, and 65 post-transplant from a technical failure, sedation complication, and pancytopenia, respectively. Recipients in Group A exhibited an average 15-fold expansion in the percent CD25+FoxP3+ of CD3+CD4+ cells in the periphery compared to an average 3-fold expansion in Group B recipients. Adding IL-6 receptor blockade to a mixed chimerism protocol has achieved tolerance of an isolated heart allograft for the first time. This protocol or a version thereof has the potential to be trialed in humans. The surprising deleterious effects of low dose IL-2 may be related to its ability to activate alloreactive T cells despite augmenting Tregs. [ABSTRACT FROM AUTHOR]

A lengthened response time when a distractor becomes a target, called negative priming, is an undisputed phenomenon in selective attention, yet just what the underlying mechanism responsible for negative priming is has not been resolved. In this study, the proportion of attended repetition trials was manipulated in order to test the predictions of three theories that have been proposed for explaining spatial negative priming: distractor suppression (e.g., Tipper, 1985), episodic memory retrieval (e.g., Neill, Valdes, & Terry, 1995), and novelty bias (e.g., Milliken, Tipper, Houghton, & Lupiáñez, 2000). The results supported the proposal that a novelty bias, which is flexible and can be overridden, is the primary mechanism responsible for priming in spatial tasks. Memory retrieval obscured the novelty bias for target processing, was more selective in older adults, and did not affect distractor processing. Novelty bias and distractor suppression may share the same inhibitory attentional mechanism. [ABSTRACT FROM AUTHOR]

Overexpression and/or mutations of oncogenes, tumour suppressor genes and tumour rejection genes have been observed in several human malignancies. Their analyses might be of diagnostic importance. Therefore, malignant hepatocytes derived from hepatocellular carcinoma (HCC) tissue as well as non-malignant hepatocytes derived from focal nodular hyperplasia (FNH) were studied. Samples containing normal human hepatocytes (HC) served as controls. Cellular material was obtained by fine-needle aspiration biopsy guided by ultrasound. Cells were analysed for expression and mutation of the oncogene MDM2, the genes GAGE-1,-2 coding for tumour-associated antigens and the candidate tumour suppressor geneFHIT. Different patterns of non-mutant FHIT transcripts including precise deletion of exons were found in 7/10 HCC, 2/10 FNH and 2/10 HC. However, expression of non-mutant GAGE-1,-2 RNA was demonstrated exclusively in 6/10 HCC samples. Further genetic features specific of HCC were point mutations in a zinc-finger motif of MDM2 (3/10 HCC samples). Neither GAGE-1,-2 expression nor MDM2 mutations were observed in the FNH samples, or in normal hepatocytes. Our findings suggest that occurrence of variable FHIT transcripts is not restricted to hepatic malignant tumours. In contrast, MDM2 mutations and GAGE-1,-2 expression were associated with HCC specimens. Therefore, the RT-PCR assays for GAGE-1,-2 and MDM2 might be useful adjuncts in cytodiagnosis of liver neoplasms. [ABSTRACT FROM AUTHOR]

Study Question: Is telomere length related to parity among a nationally representative sample of US reproductive age women?Summary Answer: History of live birth was associated with shorter telomere length.What Is Known Already: Shorter telomeres have been linked with a range of chronic health conditions and mortality and parity has been associated with health indicators. However, there is a lack of research on how parity relates to telomere length.Study Design, Size, Duration: This nationally representative, cross-sectional study included 1954 women from the National Health and Nutrition Examination Survey, 1999-2002, the only survey period which includes measurement of telomere length.Participants/materials, Setting, Methods: Women aged 20-44 were included. Parity, defined as number of previous live births, was ascertained by questionnaire. Leukocyte telomere length was measured by polymerase chain reaction and reported as a ratio in relation to standard reference DNA (T/S ratio). The relationship between leukocyte T/S ratio and parity was examined using survey weighted linear regression. Models were adjusted for race/ethnicity, age, BMI, income-to-poverty ratio, education, early age at menarche and smoking status.Main Results and the Role Of Chance: Among reproductive age women in the US, the adjusted mean leukocyte T/S ratio was 4.2% (95% CI: 0.9, 7.3) shorter in parous compared with nulliparous women. Parity was associated with 116 fewer base pairs (95% CI: 26, 204) on average, using estimated coefficients from the adjusted linear regression models and mean covariate values.Limitations Reasons For Caution: This study was cross-sectional and therefore was unable to establish temporality. The dataset lacked information on social factors, stress and fertility status, which may help explain these findings. Only two previous studies have examined this question and our findings should be interpreted with caution.Wider Implications Of the Findings: These findings in a nationally representative sample of US reproductive age women suggest that history of live birth may be associated with accelerated cellular aging. The magnitude of the observed association was greater than that of the impact of smoking or obesity on telomere length, suggesting that parity may have an independent influence on cellular aging and warrant further study.Study Funding/competing Interest(s): The study was funded in part by the Undergraduate Research Scholars Program at George Mason University. The authors have no conflicts of interest.Trial Registration Number: NA. [ABSTRACT FROM AUTHOR]

Introduction/Objective: S-ketamine is a NMDA-receptor antagonist used as anesthetic, with possibly antidepressive properties. In contrast to other anesthetics such as etomidate, propofole or meto-hexitale, it does not increase the seizure threshold. Due to its pharmacokinetic properties, S-ketamine is well suitable for short anesthesia, e.g. in electroconvulsive therapy (ECT). In our clinic we use S-ketamine and etomidate as anesthetics for ECT. The objective of this abstract is to report our clinical observations on ECT-related parameters with these two anesthetics. Methods: By the time of abstract submission, the ongoing recruitment amounts to 46 patients (15 male, 31 female) treated by 639 ECT for severe therapy-resistant major depression. Patients were anesthetized either using etomidate or S-ketamine according to clinical indication. Succinylcholine was used for muscle relaxation. A Thymatron IV stimulator (Thymatron somatics Inc., Ontario/Canada) was used for seizure provocation. Generally, patients received three treatments per week. Objective parameters recorded in each session were electrode position, stimulation energy, seizure duration, postictal supression index (PSI), maximum sustained coherence (MSC), maximal heartrate and side-effects. Statistical evaluation was performed using analysis of variance implemented in SPSS software (SPSS Statistics, 19th version, IBM Germany GmbH, Ehningen). Results: Seizure duration was significantly longer during S-ketamine that during etomidate anesthesia (41.75 and 36.65s respectively; p =0.009). Significantly lower number of restimulations was necessary during S-ketamine versus etomidate anesthesia (34 restimulations versus 20; p =0.00). Stimulation energy to induce a seizure was lower using S-ketamine compared to etomidate (230,63mC versus 259,66mC; p =0.08), but there was no statistically significant effect. Side effects were rare and did not differ between groups. Conclusion: Our preliminary data suggest that S-ketamine might have favorable effects on seizure parameters during ECT for treatment-resistant major depression concerning stimulation energy, seizure duration and number of restimulations. This is in accordance with Kranaster et al. (2011). However, interpretation is limited by the non-randomized open design. The mechanism leading to the favorable effects of s-ketamine remain unclear so far. Improvement of seizure-quality or additive antidepressive effects of S-ketamine such as observed in Zarate CA et al. (2006) and Price et al. (2009) might explain our preliminary results. [Copyright &y& Elsevier]

Atopic dermatitis (AD) is a common skin disease that affects humans and animals. Skin impairment has been described in human and canine AD. Equine AD is recognized in practice but little is known about its pathogenesis. As remarkable similarities exist across species in terms of cutaneous manifestations of AD, it was speculated that skin abnormalities may also exist in atopic horses. This case report describes the ultrastructure of the stratum corneum of two normal and two atopic horses. Biopsies were taken from sites predisposed to AD and examined using electron microscopy. Stratum corneum in normal samples was compacted with organized lipid lamellae while in atopic samples disorganized lipid lamellae, retained lamellar bodies and amorphous lipids were found. These changes are very similar to what reported in AD in other species. It is currently unknown whether these abnormalities in atopic horses are primary or secondary and their importance in allergen penetration. [ABSTRACT FROM AUTHOR]

Posttranscriptional gene silencing by RNA interference can be therapeutically exploited to inhibit pathophysiological gene expression. However, in contrast to the established effectiveness of RNAi in vitro, safe and effective delivery of siRNAs to specific organs and cell types in vivo remains the major hurdle. Here, we report the development and in vivo characterization of a novel siRNA delivery system (DACC lipoplex) suitable for modulating target gene expression specifically in the lung vasculature. Systemic administration of DACC in mice delivered siRNA cargo functionally to the lung pulmonary endothelium. A single dose of DACC lipoplexes administered by bolus injection or by infusion was sufficient to specifically silence genes expressed in pulmonary endothelial cells such as CD31, Tie-2, VE-cadherin, or BMP-R2. When tested in a mouse model for lung cancer, repeated treatment with DACC/siRNACD31 reduced formation of lung metastases and increased life span in a mouse model of experimental lung metastasis. [ABSTRACT FROM AUTHOR]

This study investigated the effects of a skin protectant solution (dimethicone 2%) on clinical signs and skin barrier function in canine atopic dermatitis (AD). Eighteen dogs with AD were randomly divided into two groups, one received dimethicone and the other received the vehicle (cyclomethicone) on selected areas (pinnae, groin, and axillae) daily for 4 weeks. Owners and investigators were blinded regarding group allocation. Clinical efficacy was evaluated using a scoring system and skin barrier by measuring the transepidermal water loss. Twelve dogs completed the study (50% drop rate in the vehicle and 20% in the dimethicone). For clinical signs, analysis of variance showed an effect of time (P < 0.005; day 0 > day 28) and region (axillae < groin < pinnae) but no effect of group or group × time interaction. For transepidermal water loss, analysis of variance showed only a main effect of region (axillae > pinnae > groin). Pearson found no correlation between transepidermal water loss and clinical scores. In this pilot study dimethicone had no significant effect on clinical signs and transepidermal water loss in canine atopic dermatitis. [ABSTRACT FROM AUTHOR]

We describe the molecular epidemiology of syphilis in San Francisco (SF) using Treponema pallidum specimens obtained from patients examined at the SF municipal sexually transmitted diseases clinic during 2004-2007. Of 69 specimens, 52 (75%) were subtype 14d9. Single subtype predominance might reflect a closely linked sexual network in SF. [ABSTRACT FROM AUTHOR]

Ovariectomy (OVX) in animal models is an accepted method to simulate postmenopausal osteoprosis. Vascular endothelial growth factor (VEGF) has been recently shown to play an important role during endochondral bone formation, hypertrophic cartilage remodeling, ossification, and angiogenesis. We hypothesized that reduced VEGF expression in bone contributes to OVX-induced bone loss and tested it in a miniature pig model and in vitro using human osteoblasts. Seventeen primiparous sows (Göttingen miniature pigs) were allocated to two experimental groups when they were 30 months old: a control group ( n = 9) and an OVX group ( n = 8). After 15 months, VEGF levels in lumbar vertebrae were measured by enzyme-linked immunosorbent assay and verified by Western blot analysis. VEGF and its receptor (VEGFR) were localized by immunohistochemistry. Expression of VEGF mRNA was analyzed by real-time reverse-transcription polymerase chain reaction. Differently sulfated glycosaminoglycans were localized in subchondral bone histochemically. Osteoblasts were immunopositive for VEGF. VEGF concentration in the vertebra was 27% lower in OVX miniature pigs. VEGFR-2 could be immunostained on osteoblasts. VEGF mRNA and protein were detectable in the lumbar vertebrae of all animals. In subchondral trabecular bone of OVX animals, significantly more islands of mineralized cartilage containing chondroitin 4- and 6-sulfate or keratan sulfate occurred compared to the control group. The occurrence of remnants of mineralized cartilage in subchondral bone of the OVX group may be caused by a delayed bone turnover due to low VEGF levels. In vitro experiments revealed an increase of VEGF in the supernatant of osteoblasts after incubation with estradiol. In conclusion, estrogen seems to be a key factor for regulation of VEGF expression in bone. Loss of VEGF due to menopause may be a reason for reduction of bone density. [ABSTRACT FROM AUTHOR]

Background: Early pregnancy loss (unintended pregnancy loss before 20 completed weeks of gestation) is a common adverse pregnancy outcome, with previous evidence reporting incidence ranging from 10 to 30% of detected pregnancies. The objective of this systematic review and meta-analysis is to determine the incidence and range of early pregnancy loss in contemporary pregnant populations based on studies with good internal and external validity. Findings may be useful for clinical counseling in pre-conception and family planning settings and for people who experience early pregnancy loss. Methods: We will search MEDLINE, EMBASE, and CINAHL databases using combinations of medical subject headings and keywords. Peer-reviewed, full-text original research articles that meet the following criteria will be included: (1) human study; (2) study designs: controlled clinical trials or observational studies with at least 100 pregnancies in the denominator, or systematic reviews of studies using these designs; (3) conducted in high-income countries; (4) reporting early pregnancy loss incidence, defined as unintended early pregnancy loss occurring prior to 20 weeks' gestation expressed as the number of losses among all pregnancies in the study period; (5) among a contemporary (1990 or later) general population of pregnancies; and (6) published between January 1, 1990, and August 31, 2021. We will assess the quality of included studies according to the United States Preventive Services Task Force Criteria for Assessing Internal and External Validity of Individual Studies. If appropriate, based on methodological comparability across included studies, we will conduct meta-analyses using random effects models to estimate the pooled incidence of early pregnancy loss among all studies with both good internal and external validity, with meta-analyses stratified by study design type (survey-based or self-reported and medical record-based), by induced abortion restrictions (restricted vs. unrestricted), and by gestational age (first trimester only vs. all gestational ages before 20 weeks). Discussion: This systematic review will synthesize existing evidence to calculate a current estimate of early pregnancy loss incidence and variability in reported incidence estimates in high-income settings. The findings of this review may inform updates to clinical counseling in pre-conception and family planning settings, as well as for patients experiencing early pregnancy loss. Systematic review registration: We have registered this review with the International Prospective Register of Systematic Reviews (PROSPERO #226267). [ABSTRACT FROM AUTHOR]

Resilience is the maintenance and/or quick recovery of mental health during and after periods of adversity. It is conceptualized to result from a dynamic process of successful adaptation to stressors. Up to now, a large number of resilience factors have been proposed, but the mechanisms underlying resilience are not yet understood. To shed light on the complex and time-varying processes of resilience that lead to a positive long-term outcome in the face of adversity, the Longitudinal Resilience Assessment (LORA) study has been established. In this study, 1191 healthy participants are followed up at 3- and 18-month intervals over a course of 4.5 years at two study centers in Germany. Baseline and 18-month visits entail multimodal phenotyping, including the assessment of mental health status, sociodemographic and lifestyle variables, resilience factors, life history, neuropsychological assessments (of proposed resilience mechanisms), and biomaterials (blood for genetic and epigenetic, stool for microbiome, and hair for cortisol analysis). At 3-monthly online assessments, subjects are monitored for subsequent exposure to stressors as well as mental health measures, which allows for a quantitative assessment of stressor-dependent changes in mental health as the main outcome. Descriptive analyses of mental health, number of stressors including major life events, daily hassles, perceived stress, and the ability to recover from stress are here presented for the baseline sample. The LORA study is unique in its design and will pave the way for a better understanding of resilience mechanisms in humans and for further development of interventions to successfully prevent stress-related disorder. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women? SUMMARY ANSWER: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders. WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear. STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. PARTICIPANTS, SETTING, METHODS: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo. MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, 21.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH. LIMITATIONS, REASONS FOR CAUTION: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. wider implications of the findings: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose. [ABSTRACT FROM AUTHOR]

Cardiac allograft tolerance in non-human primates (NHPs) has been achieved by our group via hematopoietic mixed chimerism with allogeneic bone marrow and kidney co-transplantation. This model has failed without the regulatory mechanisms associated with the donor kidney. We hypothesized that rapamycin and anti-OX40L mAb (KY1005, Kymab Ltd) could substitute for kidney co-transplantation and induce cardiac allograft tolerance by providing a favorable immunologic milieu for regulatory T cells (Tregs). Fourteen cynomolgus NHPs underwent mixed chimerism conditioning (ATGAM, total body and thymic irradiation) then organ and bone marrow transplant. Heart Alone recipients received a heart transplant (n=5), Heart/Kidney recipients received a heart and kidney co-transplant (n=7). Heart/OX40L recipients received a heart transplant plus 40 days of anti-OX40L mAb (n=2). All groups underwent a 12 day course of aCD154 mAb. The Heart Alone and Heart Kidney groups received 28 days of cyclosporine while the Heart aOX40L group received 100 days of rapamycin. All Heart Alone recipients had cellular rejection (ISHLT 3R) by 200 days post bone marrow transplant (pBMT). No Heart/Kidney recipients showed early rejection. Similarly, no Heart/OX40L recipients showed early rejection and one is currently 258 days pBMT without clinical or pathologic evidence of rejection (Figure 1). The other recipient died of viral complications. Mean peak lymphoid chimerism was 10% for the Heart Alone group, 26% for the Heart/Kidney group, and 29% for the Heart/OX40L group. The anti-OX40L protocol also showed an expansion of the Treg population with a peak of 35% Tregs in the CD4+ population. The OX40L protocol achieved robust lymphoid chimerism with concomitant expansion of Tregs. The surviving Heart/OX40L recipient achieved longer freedom from allograft rejection when compared to the Heart Alone group. OX40L costimulatory blockade may allow for heart allograft tolerance without kidney co-transplantation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Substance use has been associated with high-risk sexual behavior among men who have sex with men (MSM) both in the U.S. and around the world. Recent efforts by local organizations in San Francisco have specifically targeted methamphetamine use in this population. METHODS: We tracked methamphetamine and other substance use among men who have sex with men (MSM) in San Francisco from 2003 to 2006 using an indicator available in community outreach surveys of a prevention education program targeting MSM (n=4602). RESULTS: Overall, use of diverse substances tended to decrease from 2003 to 2006, many significantly so. Reported use of methamphetamine significantly decreased among HIV-negative MSM. However, methamphetamine and alcohol use during sex was associated with unprotected potentially HIV serodiscordant sex. CONCLUSION: Intensified prevention efforts to reduce methamphetamine use in San Francisco may be having some impact; however, strong associations of substance use and high-risk sex persist. [ABSTRACT FROM AUTHOR]