Visual-spatial cognition in women with polycystic ovarian syndrome: the role of androgens

STUDY QUESTION: Are women with polycystic ovary syndrome (PCOS) better at three-dimensional mental rotation than other women? SUMMARY ANSWER: Women with PCOS scored significantly higher on a mental rotation task than a female control group. WHAT IS KNOWN ALREADY: PCOS is a condition characterized by elevated testosterone levels. Some researches have found that three-dimensional mental rotation task performance is positively correlated with testosterone levels. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was conducted between June 2006 and January 2009. The participants were 69 women with PCOS and 41 controls recruited from five gynaecology clinics in London. The control group consisted of non-PCOS women of comparable subfertility to PCOS group. These groups sizes gave roughly 80% power to detect moderate effect sizes for the main statistical test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were recruited at London gynaecology clinics. The women were aged between 18 and 43. PCOS was diagnosed based on the Rotterdam criteria. Controls were women who experienced some degree of subfertility. Blood samples from participants were frozen for up to 4 months until being assayed by direct electrochemiluminescence. The mental rotation task was undertaken electronically. Some questionnaires and other tasks were completed as control measures. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS scored significantly higher than controls: median (range) 3.00 (0-9) and 2.00 (0-8), respectively (U = 1147.500, N1 = 69, N2 = 41, P < 0.047). Within the PCOS group, circulating levels of testosterone were significantly positively correlated with three-dimensional scoring (rs = 0.376, n = 56, P < 0.002), whereas estradiol was significantly negatively correlated with three-dimensional scoring (rs = -0.473, n = 29, P < 0.010). In the control group, the relationship between sex hormones and mental rotation was non-significant. Other factors, including general intelligence and social class, did not account for these findings. A subgroup analysis comparing hyperandrogenic PCOS cases, non-hyperandrogenic PCOS cases and controls, in which age and body mass index were controlled for using ANCOVA, found a non-significant difference in three-dimensional scoring between the three groups (F = 1.062, d.f. = 1, 73, P < 0.351). LIMITATIONS, REASONS FOR CAUTION: The small number of women in the control group meant that correlations were underpowered in this group. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to find a benefit of PCOS in visuospatial cognition, and the first to find a link between visuospatial cognition and sex hormones in PCOS. The fact that the correlations went in the opposite direction in the PCOS group compared with the controls might suggest the influence of increased prenatal exposure to androgen in PCOS. STUDY FUNDING/COMPETING INTEREST(S): The assays for this study were funded by the Department of Psychology, City University London. All authors report no conflicts of interest

Prolactin and aggression in women with fertility problems

This study tested the hypothesis that women with higher prolactin feel more hostility, anger and aggression. A total of 66 women with moderate fertility problems were grouped into the 50% who had the highest and the 50% who had the lowest levels of prolactin. Levels of hostility, aggression and anger were compared. Women with higher prolactin levels did not report significantly increased hostility. After Bonferroni correction, women with lower prolactin showed non-significantly increased scores on two measures of state anger, and on a measure of trait temper. When comparing those with the highest and lowest 20% of prolactin levels, those with lower prolactin had non-significantly higher scores on trait temper and outward expression of anger, and non-significantly lower scores for control of anger. Although non-significant, these findings run counter to those of earlier studies on this topic. Implications for future research and patient care are discussed

IgG1 Fc N-glycan galactosylation as a biomarker for immune activation.

Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc N-glycosylation varies in populations with different environmental exposures in different parts of the world. IgG Fc N-glycosylation was analysed in serum/plasma of 700 school-age children from different communities of Gabon, Ghana, Ecuador, the Netherlands and Germany. IgG1 galactosylation levels were generally higher in more affluent countries and in more urban communities. High IgG1 galactosylation levels correlated with low total IgE levels, low C-reactive protein levels and low prevalence of parasitic infections. Linear mixed modelling showed that only positivity for parasitic infections was a significant predictor of reduced IgG1 galactosylation levels. That IgG1 galactosylation is a predictor of immune activation is supported by the observation that asthmatic children seemed to have reduced IgG1 galactosylation levels as well. This indicates that IgG1 galactosylation levels could be used as a biomarker for immune activation of populations, providing a valuable tool for studies examining the epidemiological transition from communicable to non-communicable diseases

Four year experience of sarcoma of soft tissues and bones in a tertiary care hospital and review of literature

<p>Abstract</p> <p>Background</p> <p>Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones.</p> <p>Methods</p> <p>This cross sectional study was carried out at Aga Khan University Hospital from 2004 to 2008. The patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted.</p> <p>Results</p> <p>Out of 93 newly diagnosed patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed patients, 5 had soft tissue sarcoma and 9 had bone sarcoma. Mean age was 32.5 years. At presentation, approximately two third patients had localised disease while remaining one third had metastatic disease. The Kaplan Meier estimate of median recurrence free survival was 25 months, 35 months, and 44 months for Osteogenic sarcoma, Ewing's sarcoma and Chondrosarcoma respectively. For Leiomyosarcoma and Synovial sarcoma, it was 20 and 19 months respectively. The grade of the tumour (p = 0.02) and surgical margin status (p = 0.001) were statistically significant for determination of relapse of disease.</p> <p>Conclusion</p> <p>The median recurrence free survival of patients in our study was comparable to the reported literature but with significant lost to follow rate. Further large-scale, multi centre studies are needed to have a more comprehensive understanding of this heterogeneous disease in our population.</p

Interim data monitoring to enroll higher-risk participants in HIV prevention trials

<p>Abstract</p> <p>Background</p> <p>Lower-than-expected incidence of HIV undermines sample size calculations and compromises the power of a HIV prevention trial. We evaluated the effectiveness of interim monitoring of HIV infection rates and on-going modification of recruitment strategies to enroll women at higher risk of HIV in the Cellulose Sulfate Phase III study in Nigeria.</p> <p>Methods</p> <p>We analyzed prevalence and incidence of HIV and other sexually transmitted infections, demographic and sexual behavior characteristics aggregated over the treatment groups on a quarterly basis. The site investigators were advised on their recruitment strategies based on the findings of the interim analyses.</p> <p>Results</p> <p>A total of 3619 women were screened and 1644 enrolled at the Ikeja and Apapa clinics in Lagos, and at the Central and Peripheral clinics in Port Harcourt. Twelve months after study initiation, the overall incidence of HIV was less than one-third of the pre-study assumption, with rates of HIV that varied substantially between clinics. Due to the low prevalence and incidence rates of HIV, it was decided to close the Ikeja clinic in Lagos and to find new catchment areas in Port Harcourt. This strategy was associated with an almost two-fold increase in observed HIV incidence during the second year of the study.</p> <p>Conclusion</p> <p>Given the difficulties in estimating HIV incidence, a close monitoring of HIV prevalence and incidence rates during a trial is warranted. The on-going modification of recruitment strategies based on the regular analysis of HIV rates appeared to be an efficient method for targeting populations at greatest risk of HIV infection and increasing study power in the Nigeria trial.</p> <p>Trial Registration</p> <p>The trial was registered with the ClinicalTrials.gov registry under #NCT00120770 <url>http://clinicaltrials.gov/ct2/show/NCT00120770</url></p

Facilitating Next-Generation Pre-Exposure Prophylaxis Clinical Trials Using HIV Recent Infection Assays: A Consensus Statement from the Forum HIV Prevention Trial Design Project

Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases

Efficacy of vitamin D3-fortified-yogurt drink on anthropometric, metabolic, inflammatory and oxidative stress biomarkers according to vitamin D receptor gene polymorphisms in type 2 diabetic patients: a study protocol for a randomized controlled clinical trial

<p>Abstract</p> <p>Background</p> <p>Development of type 2 diabetes mellitus (T2DM) is determined by the interactions of genetic and environmental factors. This study was designed to evaluate the possible role of VDR single nucleotide polymorphisms (SNPs) on different aspects of diabetic host response (anthropometric, metabolic, oxidative stress and inflammatory) to daily intake of vitamin D through fortified yogurt drink for 12 weeks.</p> <p>Methods/Design</p> <p>This study comprises two parts: (i) a case-control study; and (ii) an intervention trial. In the first part, VDR polymorphisms <it>(Taq1</it>, <it>FokI</it>, <it>Apa1</it>, <it>Bsm1</it>, and <it>Cdx2) </it>are determined in 350 T2DM patients and 350 non-diabetic subjects. In the second part, the possible effects of daily intake of two servings of vitamin D3-fortified yogurt drink (FYD; 500 IU vitamin D/250 mL) on some selected metabolic (including insulin resistance), inflammatory and oxidative stress biomarkers in 135 T2DM patients are assessed. To relate the resulted changes in the biomarkers to vitamin D replenishment, another group of diabetic patients (n = 45) are also included in the study who receive 2 servings of plain yogurt drink (PYD) a day. The primary outcome is serum level of 25(OH) D, which it is expected to be elevated only in FYD group. Secondary outcomes include improvements in glycemic, metabolic, inflammatory and oxidative stress biomarkers in FYD group compared to PYD group. Three VDR <it>FokI </it>polymorphisms are determined only in FYD group followed by comparison of changes in the biomarkers among these genotypic variants.</p> <p>Discussion</p> <p>The present study, at least in part, elucidates the discrepancies in the results of different vitamin D-diabetes studies pertaining to the genetic variations of the population. If VDR polymorphisms are found to influence the response to our intervention, then knowing distribution of VDR polymorphisms in both diabetic and non-diabetic populations can give a picture of the proportion of the community in whom up to 1000 IU/d vitamin D may not be effective enough to improve insulin resistance and related morbidities. Therefore, they should ideally receive further nutritional support according to their genotype.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01236846">NCT01236846</a></p