The Influence of Energetic Factors on Biomarkers of Postmenopausal Breast Cancer Risk

Strong and consistent evidence exists that physical activity reduces breast cancer risk by 10-25 %, and several proposed biologic mechanisms have now been investigated in randomized, controlled, exercise intervention trials. Leading hypothesized mechanisms relating to postmenopausal breast cancer include adiposity, endogenous sex hormones, insulin resistance, and chronic low-grade inflammation. In addition, other pathways are emerging as potentially important, including those involving oxidative stress and telomere length, global DNA hypomethylation, immune function, and vitamin D exposure. Recent exercise trials in overweight/obese postmenopausal women implicate weight loss as a mechanism whereby exercise induces favorable changes in circulating estradiol levels and other biomarkers as well. Still it is plausible that some exercise-induced biomarker changes do not require loss of body fat, whereas others depend on abdominal fat loss. We highlight the latest findings from randomized, controlled trials of healthy postmenopausal women, relating exercise to proposed biomarkers for postmenopausal breast cancer risk

Leptin, adiponectin, and obesity among Caucasian and Asian women.

Ethnic differences in adipose tissue distribution may contribute to different chronic disease risks across ethnic groups, and adipokines may mediate the risk. In a cross-sectional study, we examined ethnic differences in adipokines and inflammatory markers as related to body mass index (BMI) among 183 premenopausal women with Caucasian and Asian ancestry. General linear models were used to estimate adjusted mean levels of leptin, adiponectin, interleukin-6, and C-reactive protein (CRP). Asian women had significantly lower serum levels of leptin, adiponectin, and CRP than Caucasian participants (P≤.01) across all levels of BMI. Among overweight and obese women, Asians showed a stronger association of CRP with leptin (β=1.34 versus β=0.64) and with adiponectin (β=-0.95 versus β=-0.75) than Caucasians. Compared to Caucasians of similar BMI, Asians may experience a higher chronic disease risk due to lower levels of adiponectin despite their lower levels of leptin

Associations between obesity and serum lipid-soluble micronutrients among premenopausal women.

Elucidating potential pathways that micronutrients may reduce/promote chronic disease may contribute to our understanding of the underlying etiology of disease and their utility as markers of risk. In the current study, we examined associations of serum lipid-soluble micronutrients with body mass index (BMI). We hypothesized that obesity may differentially influence serum micronutrient levels, thereby affecting risk for chronic disease incidence and mortality. Baseline serum samples from 180 premenopausal women from a nutritional trial were analyzed for leptin, C-reactive protein, 25-hydroxyvitamin D, carotenoids, and tocopherols. Participants were stratified into normal-weight (18.5-24.9), overweight (25-29.9), and obese (>or=30) subgroups by BMI (in kilograms per square meter). Differences in serum biomarkers among BMI subgroups were adjusted for Asian ethnicity and smoking status. As expected, obese individuals had significantly higher serum levels of leptin and C-reactive protein (Ps < .05) compared with normal-weight women. gamma-Tocopherol levels were significantly higher in obese individuals (P < .05), whereas alpha-tocopherol levels did not differ among BMI subgroups. Serum levels of 25-hydroxyvitamin D and carotenoids (except lycopene) were significantly lower in obese than in normal-weight women (Ps < .05). The associations between BMI and carotenoids were independent of dietary intake. The obesity-associated reduction for total provitamin A carotenoids (45%) was approximately 3-fold greater than that observed for non-provitamin A carotenoids (16%). Our results indicate potential influences of obesity on serum levels of lipid-soluble micronutrients and suggest that metabolism of provitamin A carotenoids may contribute to the differences observed

Common Genetic Variants Are Associated with Accelerated Bone Mineral Density Loss after Hematopoietic Cell Transplantation

BACKGROUND: Bone mineral density (BMD) loss commonly occurs after hematopoietic cell transplantation (HCT). Hypothesizing that genetic variants may influence post-HCT BMD loss, we conducted a prospective study to examine the associations of single nucleotide polymorphisms (SNP) in bone metabolism pathways and acute BMD loss after HCT. METHODS AND FINDINGS: We genotyped 122 SNPs in 45 genes in bone metabolism pathways among 121 autologous and allogeneic HCT patients. BMD changes from pre-HCT to day +100 post-HCT were analyzed in relation to these SNPs in linear regression models. After controlling for clinical risk factors, we identified 16 SNPs associated with spinal or femoral BMD loss following HCT, three of which have been previously implicated in genome-wide association studies of bone phenotypes, including rs2075555 in COL1A1, rs9594738 in RANKL, and rs4870044 in ESR1. When multiple SNPs were considered simultaneously, they explained 5-35% of the variance in post-HCT BMD loss. There was a significant trend between the number of risk alleles and the magnitude of BMD loss, with patients carrying the most risk alleles having the greatest loss. CONCLUSION: Our data provide the first evidence that common genetic variants play an important role in BMD loss among HCT patients similar to age-related BMD loss in the general population. This infers that the mechanism for post-HCT bone loss is a normal aging process that is accelerated during HCT. A limitation of our study comes from its small patient population; hence future larger studies are warranted to validate our findings

Left versus right subcallosal cingulate deep brain stimulation for treatment-resistant depression

Deep brain stimulation (DBS) of the subcallosal cingulate has emerged as a promising therapy for treatment-resistant depression (TRD). To date, all studies have employed bilateral stimulation; however, the physiology of affect and pathophysiology of depression are known to be asymmetric across hemispheres. Unilateral stimulation may provide efficacy while decreasing risk. Five patients were exposed to unilateral open-label DBS to the subcallosal cingulate for 12 weeks each to the left and then right hemispheres in a double-blind, crossover fashion. After 12 weeks of stimulation to each hemisphere, bilateral stimulation was initiated, and patients were followed for 12 additional weeks. Additionally, nine months of long-term follow up data were collected. Left, but not right, unilateral stimulation was associated with significant decrease in depression scores; with bilateral stimulation, all patients improved and one patient remitted. No serious adverse events were associated with surgery or acute or chronic stimulation. This small study suggests that unilateral DBS to the subcallosal cingulate may be an effective treatment for TRD. All patients improved with bilateral stimulation, though antidepressant effects following 12 weeks were modest. These findings contrast somewhat with prior open-label trials, though duration of bilateral stimulation was shorter in this trial. The current study continues to confirm safety of implantation and use of DBS to the subcallosal cingulate for patients with TRD and highlights the importance of personalization of therapy, for example by hemisphere, in future trials

Active, but not passive cigarette smoking was inversely associated with mammographic density

The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women’s Health Across the Nation (SWAN). We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked ≥20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked ≥20 cigarettes/day was associated with 23.8% lower density, compared to having smoked ≤9 cigarettes/day (p &lt; 0.001). Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density

What explains gender inequalities in HIV/AIDS prevalence in sub-Saharan Africa? Evidence from the demographic and health surveys

Abstract Background Women are disproportionally affected by human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa (SSA). The determinants of gender inequality in HIV/AIDS may vary across countries and require country-specific interventions to address them. This study aimed to identify the socio-demographic and behavioral characteristics underlying gender inequalities in HIV/AIDS in 21 SSA countries. Methods We applied an extension of the Blinder-Oaxaca decomposition approach to data from Demographic and Health Surveys and AIDS Indicator Surveys to quantify the differences in HIV/AIDS prevalence between women and men attributable to socio-demographic factors, sexual behaviours, and awareness of HIV/AIDS. We decomposed gender inequalities into two components: the percentage attributable to different levels of the risk factors between women and men (the “composition effect”) and the percentage attributable to risk factors having differential effects on HIV/AIDS prevalence in women and men (the “response effect”). Results Descriptive analyses showed that the difference between women and men in HIV/AIDS prevalence varied from a low of 0.68 % (P = 0.008) in Liberia to a high of 11.5 % (P < 0.001) in Swaziland. The decomposition analysis showed that 84 % (P < 0.001) and 92 % (P < 0.001) of the higher prevalence of HIV/AIDS among women in Uganda and Ghana, respectively, was explained by the different distributions of HIV/AIDS risk factors, particularly age at first sex between women and men. In the majority of countries, however, observed gender inequalities in HIV/AIDS were chiefly explained by differences in the responses to risk factors; the differential effects of age, marital status and occupation on prevalence of HIV/AIDS for women and men were among the significant contributors to this component. In Cameroon, Guinea, Malawi and Swaziland, a combination of the composition and response effects explained gender inequalities in HIV/AIDS prevalence. Conclusions The factors that explain gender inequality in HIV/AIDS in SSA vary by country, suggesting that country-specific interventions are needed. Unmeasured factors also contributed substantially to the difference in HIV/AIDS prevalence between women and men, highlighting the need for further study

Accelerated Evolution of the Prdm9 Speciation Gene across Diverse Metazoan Taxa

The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark of speciation. One of the earliest postzygotic isolating barriers to arise between incipient species is the sterility of the heterogametic sex in interspecies' hybrids. Four genes that underlie hybrid sterility have been identified in animals: Odysseus, JYalpha, and Overdrive in Drosophila and Prdm9 (Meisetz) in mice. Mouse Prdm9 encodes a protein with a KRAB motif, a histone methyltransferase domain and several zinc fingers. The difference of a single zinc finger distinguishes Prdm9 alleles that cause hybrid sterility from those that do not. We find that concerted evolution and positive selection have rapidly altered the number and sequence of Prdm9 zinc fingers across 13 rodent genomes. The patterns of positive selection in Prdm9 zinc fingers imply that rapid evolution has acted on the interface between the Prdm9 protein and the DNA sequences to which it binds. Similar patterns are apparent for Prdm9 zinc fingers for diverse metazoans, including primates. Indeed, allelic variation at the DNA–binding positions of human PRDM9 zinc fingers show significant association with decreased risk of infertility. Prdm9 thus plays a role in determining male sterility both between species (mouse) and within species (human). The recurrent episodes of positive selection acting on Prdm9 suggest that the DNA sequences to which it binds must also be evolving rapidly. Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis. We propose a hypothetical model in which incompatibilities between Prdm9-binding specificity and satellite DNAs provide the molecular basis for Prdm9-mediated hybrid sterility. We suggest that Prdm9 should be investigated as a candidate gene in other instances of hybrid sterility in metazoans

Southeastern Association of Law Libraries Annual Meeting

The 2009 SEAALL Annual Meeting was held in Athens Georgia, April 16-18, 2009