The Contribution of Benzene to Smoking-Induced Leukemia

Cigarette smoking is associated with an increased risk of leukemia; benzene, an established leukemogen, is present in cigarette smoke. By combining epidemiologic data on the health effects of smoking with risk assessment techniques for low-dose extrapolation, we assessed the proportion of smoking-induced total leukemia and acute myeloid leukemia (AML) attributable to the benzene in cigarette smoke. We fit both linear and quadratic models to data from two benzene-exposed occupational cohorts to estimate the leukemogenic potency of benzene. Using multiple-decrement life tables, we calculated lifetime risks of total leukemia and AML deaths for never, light, and heavy smokers. We repeated these calculations, removing the effect of benzene in cigarettes based on the estimated potencies. From these life tables we determined smoking-attributable risks and benzene-attributable risks. The ratio of the latter to the former constitutes the proportion of smoking-induced cases attributable to benzene. Based on linear potency models, the benzene in cigarette smoke contributed from 8 to 48% of smoking-induced total leukemia deaths [95% upper confidence limit (UCL), 20-66%], and from 12 to 58% of smoking-induced AML deaths (95% UCL, 19-121%). The inclusion of a quadratic term yielded results that were comparable; however, potency models with only quadratic terms resulted in much lower attributable fractions--all < 1%. Thus, benzene is estimated to be responsible for approximately one-tenth to one-half of smoking-induced total leukemia mortality and up to three-fifths of smoking-related AML mortality. In contrast to theoretical arguments that linear models substantially overestimate low-dose risk, linear extrapolations from empirical data over a dose range of 10- to 100-fold resulted in plausible predictions

Mechanisms of Impaired Exercise Capacity in Short Duration Experimental Hyperthyroidism

Abstract To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26±1 yr (mean±SE) before and after 2 wk of daily ingestion of 100 pg of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P &lt; 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08±0.17 vs. 2.94±0.19 l/min; P &lt; 0.001) despite increased heart rate and cardiac output at maximal exercise (P &lt; 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P &lt; 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P &lt; 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P &lt; 0.001) and glycolytic (P &lt; 0.05) enzymes in skeletal muscle and a 15% decrease in type 11A muscle fiber cross-sectional area (P &lt; 0.05). Lean body mass was reduced (P &lt; 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P &lt; 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced. (J. Clin

Perfluorinated alkyl acids and fecundity assessment in striped mullet (\u3ci\u3eMugil cephalus\u3c/i\u3e) at Merritt Island national wildlife refuge

This study investigated wild caught striped mullet (Mugil cephalus) at Merritt Island National Wildlife Refuge (MINWR) for levels of 15 perfluoroalkyl acids (PFAA) in tandem with individual fecundity measurements (Oocyte sub-stage 2 late, n=42) and oocyte reproductive stages (Stages 1–5, n=128). PFAAmeasurementswere quantified in stripedmullet liver (n=128),muscle (n=49), and gonad (n=10). No significant negative impacts of liver PFAA burden on wild-caught,mullet fecundity endpoints were observed in this study; however, changes in PFAAwere observed in the liver asmullet progressed through different sub-stages of oocyte development. Of the PFAA with significant changes by sub-stage of oocyte development, the carboxylic acids (perfluorooctanoic acid, perfluorononanoic acid, and perfluorotridecanoic acid) increased in the liver with increasing sub-stage while the sulfonic acid and its precursor (perfluorooctanesulfonic acid (PFOS) and perfluorooctanesulfonamide, respectively) decreased in the liver with increasing sub-stage of oocyte development. This is a unique find and suggests PFAA change location of compartmentalization as mullet progress towards spawning. Investigations also revealed higher than expected median muscle and gonad levels of PFOS in striped mullet collected at MINWR (9.01 ng/g and 80.2 ng/g, respectively)

Socio-demographic predictors of gender inequality among heterosexual couples expecting a child in south-central Uganda

Background: Gender inequality is a pervasive problem in sub-Saharan Africa, and has negative effects on health and development. Objective: Here, we sought to identify socioeconomic predictors of gender inequality (measured by low decision-making power and high acceptance of intimate partner violence) within heterosexual couples expecting a child in south-central Uganda. Method: We used data from a two-arm cluster randomized controlled HIV self-testing intervention trial conducted in three antenatal clinics in south-central Uganda among 1,618 enrolled women and 1,198 male partners. Analysis included Cochran Mantel-Haenzel, proportional odds models, logistic regression, and generalized linear mixed model framework to account for site-level clustering. Results: Overall, we found that 31.1% of men had high acceptance of IPV, and 15.9% of women had low decision-making power. We found religion, education, HIV status, age, and marital status to significantly predict gender equality. Specifically, we observed lower gender equality among Catholics, those with lower education, those who were married, HIV positive women, and older women. Conclusion: By better understanding the prevalence and predictors of gender inequality, this knowledge will allow us to better target interventions (increasing education, reducing HIV prevalence in women, targeting interventions different religions and married couples) to decrease inequalities and improve health care delivery to underserved populations in Uganda

Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.

Stressors motivate an array of adaptive responses ranging from \u27fight or flight\u27 to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF\u27s capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders

Self-rated health and quality of life in female sex workers with substance use disorders in Tehran, Iran

Abstract Background While self-rated health (SRH) and quality of life (QoL) has been associated with substance use disorders (SUDs) in sex-working populations, little is known about this association in Iran. This study aimed to assess QoL and SRH in Iranian female sex workers (FSWs) in Tehran. Method FSWs were recruited using convenience sampling methods from substance abuse treatment centers in Tehran that exclusively provided services for women. Participants completed an interviewer-administered demographic questionnaire in Persian and the Iranian version of the Short Form Health Survey (SF-36). Descriptive analyses, means and standard deviations; frequency and percentages, t-test and one-way ANOVA, and Chi-square tests were utilized to analyze the data. Results The mean age among 161 participants clinically diagnosed with SUD was 34.09 years (SD 7.97; range: 18–57). The total mean QoL score was 41.03 (SD: 12.92). The highest and lowest mean scores were observed in the physical functioning (52.23) and role emotional (26.64) dimensions, respectively. Significant differences (p < 0.05) in QoL were observed according to education and marital status, and the average QoL score was lower in women who reported permanent marriages and women who were illiterate. The average score of QoL was significantly higher in employed women. Overall, 51.6% of the women rated their health as sub-optimal, with divorced participants and women who were illiterate more likely to rate their health as sub-optimal (p < 0.05). Conclusion Results emphasize the need for mental, physical, and sexual health screening and gender-specific interventions to improve QoL in this population. Further investigation may elucidate the consequences of poor SRH and QoL on SUD treatment adherence, sexual risk behavior, and morbidity and mortality in FSWs

Replication files for Male circumcision and HIV acquisition: re-investigating the evidence from young men in Kisumu, Kenya

This dataset contains the Stata codes for the replication study, “Male circumcision and HIV acquisition: re-investigating the evidence from young men in Kisumu, Kenya.” These Stata codes were used to produce tables and figures included in the replication paper. The paper was funded by 3ie’s Replication Window, supported by the Bill and Melinda Gates Foundation, which will be published in the 3ie Replication Paper Series. The datasets used in the replication paper are not publicly available but can be obtained by request through The National Technical Information Service (NTIS) (http://www.ntis.gov/). The name of the dataset under The National Technical Information Service (NTIS) is: Randomized Control Trial of Male Circumcision to Reduce HIV Incidence in Kisumu, Kenya. PB2013500016 NTIS Issue Number 20131