Integrative assessment of low-dose gamma radiation effects on <i>Daphnia magna</i> reproduction: Toxicity pathway assembly and AOP development

High energy gamma radiation is potentially hazardous to organisms, including aquatic invertebrates. Although extensively studied in a number of invertebrate species, knowledge on effects induced by gamma radiation is to a large extent limited to the induction of oxidative stress and DNA damage at the molecular/cellular level, or survival, growth and reproduction at the organismal level. As the knowledge of causal relationships between effects occurring at different levels of biological organization is scarce, the ability to provide mechanistic explanation for observed adverse effects is limited, and thus development of Adverse Outcome Pathways (AOPs) and larger scale implementation into next generation hazard and risk predictions is restricted. The present study was therefore conducted to assess the effects of high-energy gamma radiation from cobalt-60 across multiple levels of biological organization (i.e., molecular, cellular, tissue, organ and individual) and characterize the major toxicity pathways leading to impaired reproduction in the model freshwater crustacean Daphnia magna (water flea). Following gamma exposure, a number of bioassays were integrated to measure relevant toxicological endpoints such as gene expression, reactive oxygen species (ROS), lipid peroxidation (LPO), neutral lipid storage, adenosine triphosphate (ATP) content, apoptosis, ovary histology and reproduction. A non-monotonic pattern was consistently observed across the levels of biological organization, albeit with some variation at the lower end of the dose-rate scale, indicating a complex response to radiation doses. By integrating results from different bioassays, a novel pathway network describing the key toxicity pathways involved in the reproductive effects of gamma radiation were proposed, such as DNA damage-oocyte apoptosis pathway, LPO-ATP depletion pathway, calcium influx-endocrine disruption pathway and DNA hypermethylation pathway. Three novel AOPs were proposed for oxidative stressor-mediated excessive ROS formation leading to reproductive effect, and thus introducing the world's first AOPs for non-chemical stressors in aquatic invertebrates.publishedVersio

Surveillance of Transmitted Antiretroviral Drug Resistance among HIV-1 Infected Women Attending Antenatal Clinics in Chitungwiza, Zimbabwe

The rapid scale-up of highly active antiretroviral therapy (HAART) and use of single dose Nevirapine (SD NVP) for prevention of mother-to-child transmission (pMTCT) have raised fears about the emergence of resistance to the first line antiretroviral drug regimens. A cross-sectional study was conducted to determine the prevalence of primary drug resistance (PDR) in a cohort of young (<25 yrs) HAART-naïve HIV pregnant women attending antenatal clinics in Chitungwiza, Zimbabwe. Whole blood was collected in EDTA for CD4 counts, viral load, serological estimation of duration of infection using the BED Calypte assay and genotyping for drug resistance. Four hundred and seventy-one women, mean age 21 years; SD: 2.1 were enrolled into the study between 2006 and 2007. Their median CD4 count was 371cells/µL; IQR: 255–511 cells/µL. Two hundred and thirty-six samples were genotyped for drug resistance. Based on the BED assay, 27% were recently infected (RI) whilst 73% had long-term infection (LTI). Median CD4 count was higher (p<0.05) in RI than in women with LTI. Only 2 women had drug resistance mutations; protease I85V and reverse transcriptase Y181C. Prevalence of PDR in Chitungwiza, 4 years after commencement of the national ART program remained below WHO threshold limit (5%). Frequency of recent infection BED testing is consistent with high HIV acquisition during pregnancy. With the scale-up of long-term ART programs, maintenance of proper prescribing practices, continuous monitoring of patients and reinforcement of adherence may prevent the acquisition and transmission of PDR

Association between BMI and periodontitis in women living with or at risk for HIV

Aims: Currently, there is no data available assessing the association between body mass index (BMI) and periodontitis among women living with HIV (WLWH). This study aims to investigate this association among WLWH and women at risk for HIV (WRH) in the United States. Methods and results: Data from 351 WLWH and 52 WRH participants from the Women's Interagency HIV Study having pocket depths and clinical periodontal attachment loss assessments in 2003–2004 were included. Multinomial logistic regression analyses in the full sample assessed the relationship between BMI (underweight/normal, overweight, or obese) and periodontitis by severity (mild, moderate, severe), adjusting for study sites, age, education, annual household income, smoking, alcohol consumption, and diabetes. Overall, 75.2% women (76.0% WLWH; 69.0% WRH) had periodontitis. Moreover, 75.0% obese and 75.3% overweight women were affected by periodontitis. In the full sample, adjusted odds ratio (aOR) of having mild, moderate, and severe periodontitis in obese women were: 1.14 (95% confidence interval [CI]: 0.51–2.52), 1.02 (95% CI: 0.46–2.29), and 0.24 (95% CI: 0.06–1.07), respectively, and in overweight women: 0.70 (95% CI: 0.31–1.58), 0.85 (95% CI: 0.38–1.90), and 0.31 (95% CI: 0.08–1.15), respectively. Conclusions: Even with high prevalence of periodontitis among women with or without HIV infection in this cohort, this study does not provide evidence of an association between BMI and periodontitis

The effect of unstable housing on HIV treatment biomarkers: An instrumental variables approach

Unstable housing, including homelessness, is a public policy concern for all populations, and more critically for people with a serious health condition such as HIV. We measure the effect of unstable housing on HIV treatment biomarkers: viral suppression (viral load &lt; 200 HIV RNA copies per ml) and adequate CD4+ T-cell count (CD4&gt;350 cells per μl). We use panel data (1995–2015) from 3082 participants of the Women's Interagency HIV Study (WIHS) sites in Bronx and Brooklyn (NY), Chicago (IL), Los Angeles and San Francisco (CA), and Washington (DC). The instrumental variable (IV) measures allocations for the Housing Opportunities for People with AIDS (HOPWA) per person newly infected with HIV, and it represents actual availability of housing assistance for HIV-positive persons at the metropolitan area level. Using an extended probit model with the IV, we find that unstable housing reduces the likelihood of viral suppression by 51 percentage points, and decreases the probability of having adequate CD4 cell count by 53 percentage points. The endogeneity-corrected results are larger than naïve probits, which show decreases of 8.1 and 7.8 percentage points, respectively. The hypothesized pathways for the effect are: decreased use of mental healthcare/counseling, any healthcare, and less continuity of care. Increasing efforts to improve housing assistance, including HOPWA, and other interventions to make housing more affordable for low-income populations, and HIV-positive populations in particular, may be warranted not only for the benefits of stable housing, but also to improve HIV-related biomarkers

Substance use and its predictors among undergraduate medical students of Addis Ababa University in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Substance use remains high among Ethiopian youth and young adolescents particularly in high schools and colleges. The use of alcohol, <it>khat </it>and tobacco by college and university students can be harmful; leading to decreased academic performance, increased risk of contracting HIV and other sexually transmitted diseases. However, the magnitude of substance use and the factors associated with it has not been investigated among medical students in the country. This study was conducted to determine the prevalence of substance use and identify factors that influenced the behavior among undergraduate medical students of Addis Ababa University in Ethiopia.</p> <p>Methods</p> <p>A cross-sectional study using a pre-tested structured self-administered quantitative questionnaire was conducted in June 2009 among 622 medical students (Year I to Internship program) at the School of Medicine. The data were entered into Epi Info version 6.04d and analyzed using SPSS version 15 software program. Descriptive statistics were used for data summarization and presentation. Differences in proportions were compared for significance using Chi Square test, with significance level set at p < 0.05. Multivariate logistic regression analyses were used to assess the magnitude of associations between substance use and socio-demographic and behavioral correlates.</p> <p>Results</p> <p>In the last 12 months, alcohol was consumed by 22% (25% males vs. 14% females, p = 0.002) and <it>khat </it>use was reported by 7% (9% males vs. 1.5% females, p < 0.001) of the students. About 9% of the respondents (10.6% males vs. 4.6% females, p = 0.014) reported ever use of cigarette smoking, and 1.8% were found to be current smokers. Using multiple logistic regression models, being male was strongly associated with alcohol use in the last 12 months (adjusted OR = 2.14, 95% CI = 1.22-3.76). Students whose friends currently consume alcohol were more likely to consume alcohol (adjusted OR = 2.47, 95% CI = 1.50-4.08) and whose friends' use tobacco more likely to smoke (adjusted OR = 3.89, 95% CI = 1.83-8.30). <it>Khat </it>use within the past 12 months was strongly and positively associated with alcohol consumption (adjusted OR = 15.11, 95% CI = 4.24-53.91). Similarly, ever use of cigarette was also significantly associated with alcohol consumption (adjusted OR = 8.65, 95% CI = 3.48-21.50).</p> <p>Conclusions</p> <p>Concordant use of alcohol, <it>khat </it>and tobacco is observed and exposure to friends' use of substances is often implicated. Alcohol consumption or <it>khat </it>use has been significantly associated with tobacco use. While the findings of this study suggest that substance use among the medical students was not alarming, but its trend increased among students from Year I to Internship program. The university must be vigilant in monitoring and educating the students about the consequences of substance use.</p

The Impact of Cumulative Depression Along the HIV Care Continuum in Women Living with HIV during the Era of Universal Antiretroviral Treatment

Background: Data are limited on cumulative impacts of depression on engagement in care and HIV outcomes in women living with HIV (WLWH) during the era of universal antiretroviral therapy (ART). Understanding the relationship of accumulated depression with HIV disease management may help identify benefits of interventions to reduce severity and duration of depressive episodes. Setting: A cohort of WLWH (N = 1491) from the Women's Interagency HIV Study at 9 sites across the US.Methods:This longitudinal observational cohort study (2013-2017) followed WLWH for a maximum of 9 semiannual visits. Depression was quantified as a time-updated measure of percent of days depressed (PDD) created from repeated assessments using the Center for Epidemiologic Studies Depression scale. Marginal structural Poisson regression models were used to estimate the effects of PDD on the risks of missing an HIV care appointment, <95% ART adherence, and virological failure (≥200 copies/mL). Results: The risk of missing an HIV care appointment [risk ratio (RR) = 1.16, 95% confidence interval = 0.93 to 1.45; risk difference (RD) = 0.01, -0.01 to 0.03], being <95% ART adherent (RR = 1.27, 1.06-1.52; RD = 0.04, -0.01 to 0.07), and virological failure (RR = 1.09, 1.01-1.18; RD = 0.01, -0.01 to 0.03) increased monotonically with increasing PDD (comparing those with 25 to those with 0 PDD). The total effect of PDD on virological failure was fully (%100) mediated by being <95% ART adherent. Conclusions: Time spent depressed increases the risk of virological failure through ART adherence, even in the era of universal ART regimes forgiving of imperfect adherence

Hormone therapy and fractures in postmenopausal women

Background:Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.Methods:A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).Results:At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy (P = 0.69) and HIV status (P = 0.53) were not.Conclusion:Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes