Consortium analysis of 7 candidate SNPs for ovarian cancer

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.     

Intra-articular dislocation of the patella: two cases and literature review.

Intra-articular dislocation of the patella remains uncommon and is generally thought to be a problem of young adolescent males. This report reminds emergency physicians that it can occur in the arthritic knee, and it should be considered in the differential diagnosis of locked knee in the elderly. Closed reduction should be attempted in these cases, because the dislocation is liable to be held in place by osteophytes rather than impaction of the patella deep in the intercondylar notch and a good functional outcome can be expected.     

Perfusion-based functional magnetic resonance imaging with single-shot RARE and GRASE acquisitions.

For perfusion-based functional magnetic resonance imaging, the previously introduced flow-sensitive alternating inversion recovery (FAIR) technique is combined with single-shot RARE (rapid acquisition with relaxation enhancement) and GRASE (gradient and spin echo) imaging sequences. The advantages of these sequences compared to commonly used echo-planar imaging (EPI) are an increased signal-to-noise ratio and the absence of distortions and artifacts due to magnetic field inhomogeneities. RARE- and GRASE-FAIR are applied to functional brain mapping studies in humans during visual stimulation. Results demonstrate that the presented techniques allow for perfusion maps with higher spatial resolution compared to EPI-FAIR. Relative regional cerebral blood flow change in the occipital cortex during visual stimulation was measured to be 41+/-4% (n = 5). The comparison of FAIR data obtained with RARE and GRASE techniques shows that RARE yields images with the higher signal-to-noise ratio. However, the GRASE technique features a shorter acquisition time and less RF power deposition and is thus better suited for multi-slice acquisitions.     

HIV prevention: better choice for better coverage

IntroductionAntiretroviral‐based pre‐exposure prophylaxis (PrEP) is today an established, effective and safe method of HIV prevention used in multiple countries worldwide by a broad range of populations at risk of HIV infection. Biomedical innovations are critical in supporting the primary prevention of HIV; however, their potential can only be maximized if end‐user challenges are recognized, described and used to develop next‐generation models.DiscussionFirst‐generation PrEP, a daily oral pill, is highly efficacious, discreet and affords users the ability to commence and conclude treatment rapidly. However, consistent daily adherence and persistence is challenging, especially among younger populations, due in part to side effects, the risk of stock‐outs and a lack of pill storage options. Second‐generation PrEP, longer acting agents that require less frequent dosing, could overcome such challenges. Agents that have shown efficacy in clinical trials include a monthly vaginal ring and PrEP injectables to be administered every 8 weeks, while products in development include 6 monthly injectables, oral therapy that uses monthly rather than daily pills, implants and the potential for long‐acting passive immunization.ConclusionsSecond‐generation PrEP agents will have the potential to offer improved adherence and less frequent reminders once they have undergone further development and the delivery systems that will best support them have been established. In order to pursue global UNAIDS targets of reducing new HIV infections to fewer than 500,000 annually by 2025, and to ensure that all people have access to prevention options that meet their specific prevention needs, both early and next‐generation PrEP options are needed.     

Epidemiology of soy exposures and breast cancer risk

Most of the early studies published on soy and breast cancer were not designed to test the effect of soy; the assessment of soy intake was usually crude and few potential confounders were considered in the analysis. In this review, we focused on studies with relatively complete assessment of dietary soy exposure in the targeted populations and appropriate consideration for potential confounders in the statistical analysis of study data. Meta-analysis of the 8 (1 cohort, 7 case-control) studies conducted in high-soy-consuming Asians show a significant trend of decreasing risk with increasing soy food intake. Compared to the lowest level of soy food intake (or=20 mg isoflavones per day). In contrast, soy intake was unrelated to breast cancer risk in studies conducted in the 11 low-soy-consuming Western populations whose average highest and lowest soy isoflavone intake levels were around 0.8 and 0.15 mg per day, respectively. Thus, the evidence to date, based largely on case-control studies, suggest that soy food intake in the amount consumed in Asian populations may have protective effects against breast cancer.     

Age,reproductive history,seasonality, and maternal body composition during pregnancy for nomadic Turkana of Kenya

To evaluate the potential differences in maternal nutritional investment in pregnancy, data collected from nomadic Ngisonyoka Turkana women during a July 1993–July 1994 field season were utilized. The roles maternal age, parity, duration of the previous nonpregnant interval, overlap between pregnancy and lactation on trimester changes in weight and summed skinfolds during pregnancy were examined. Because seasonality is an important aspect of the Turkana environment, the effects of seasonality were also assessed. First trimester weight gain is positively associated with overlap in pregnancy and lactation. Second trimester maternal weight gain is negatively influenced by higher parity and by overlap between lactation and early pregnancy. Third trimester weight gain is influenced only by seasonally induced morbidity. First trimester changes in maternal skinfolds are negatively influenced by older maternal age and parity, and positively influenced by a longer nonpregnant interval, and overlap between pregnancy and lactation. Second and third trimester skinfolds are significantly associated only with overlap between lactation and pregnancy (negatively in the second, positively in the third). Seasonality does not influence maternal skinfolds. Differences in age- and parity-related patterns of maternal nutritional investment in pregnancy are not supported by the data. The possibility that Turkana cultural beliefs may influence nutritional status during pregnancy is discussed. Am. J. Hum. Biol. 11:658–672, 1999. © 1999 Wiley-Liss, Inc.     

Drive for thinness in black and white preadolescent girls

This study examined racial differences in drive for thinness, a motivational variable implicated in the etiology of eating disorders. Subjects included 613 black and white preadolescent girls from one of three National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study centers. Instruments included the Drive for Thinness Scale, a Criticism about Weight scale, the Self-Perception Profile for Children, a Sexual Maturation index, and 3-day food diaries. Black girls reported significantly greater drive for thinness than white girls. Drive for thinness was significantly associated with adiposity in both groups; additional predictors included criticism about weight for black girls and dissatisfaction with physical appearance for white girls. Correlations between drive for thinness and nutrient intakes were not significant. The finding of a greater drive for thinness among young black girls is provocative, given the higher prevalence of obesity and the lower prevalence of anorexia nervosa among black women. Longitudinal follow-up will examine the significance of drive for thinness in the development of weight and eating disorders in this cohort. © 1995 by John Wiley & Sons, Inc.