Risk factors for Barrett’s esophagus among patients with gastroesophageal reflux disease: A community clinic-based case-control study

Objective: To measure the relative risks of Barrett’s esophagus (BE) associated with demographic factors, measures of adiposity and smoking among patients with gastroesophageal reflux disease (GERD). Methods: Patients newly diagnosed with specialized intestinal metaplasia (SIM) (n=197) were compared to patients with GERD (n= 418) in a community clinic-based case-control study. Case sub-groups included those with any visible columnar epithelium (VBE) (n=97), and those with a long segment (=2cm) of columnar epithelium (LSBE) (n=54). Results: Risks increased with older age (adjusted odds ratio (aOR) per decade for SIM=1.3, 95% confidence interval (CI)= 1.1-1.5; VBE aOR=1.4 ,CI=1.1-1.6; LSBE aOR=1.5, CI=1.2-1.9), male gender (SIM aOR=1.5, CI=1.1-2.2; VBE aOR=2.7, CI=1.6-4.5; LSBE aOR=3.9, CI=1.9- 8.1) and possibly Asian race. Increased risk of BE in particular was observed with high waist-tohip ratio (WHR, male high: =0.9, female high: =0.8) (SIM aOR=1.3, CI=0.9-2.1; VBE aOR=1.9, CI=1.0-3.5; LSBE aOR=4.1, CI=1.5-11.4). These associations were independent of body mass index (BMI) for the VBE and LSBE case groups but not for SIM which was the only case group in which BMI was a significant risk factor. Ever smoking cigarettes increased risk similarly for all case groups (SIM aOR=1.8, CI=1.2-2.6; VBE aOR=1.6, CI=1.0-2.6; LSBE aOR=2.6, CI=1.3- 4.9), although dose response relationship was not detected for duration or intensity of smoking. Conclusions: Older age, male gender and history of smoking increased risk of SIM and BE among GERD patients independent of other risk factors for BE. Central adiposity was most strongly related to risk of VBE and LSBE. These results may be useful in development of risk profiles for screening GERD patients

Abstinence promotion under PEPFAR: The shifting focus of HIV prevention for youth

Abstinence-until-marriage (AUM) – strongly supported by religious conservatives in the U.S. - became a key element of initial HIV prevention efforts under the President’s Emergency Plan for AIDS Relief (PEPFAR). AUM programs have demonstrated limited efficacy in changing behaviors, promoted medically inaccurate information, and withheld life-saving information about risk reduction. A focus on AUM also undermined national efforts in Africa to create integrated youth HIV prevention programs. PEPFAR prevention efforts after 2008 shifted to science-based programming, however vestiges of AUM remain. Primary prevention programs within PEPFAR are essential and nations must be able to design HIV prevention based on local needs and prevention science

The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia

The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension1, 2, 3. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension

Adolescent Risk-Taking, Cancer Risk, and Life Course Approaches to Prevention

AbstractAdolescent risk-taking may have long-term consequences for adult cancer risk. Behaviors such as smoking and sexual activity, commonly initiated during adolescence, may result—decades later—in cancer. Life course epidemiology focuses on unique vulnerabilities at specific development periods and their importance to later development of disease. A life course epidemiological perspective that integrates social and biological risk processes can help frame our understanding how specific adult cancers develop. Moreover, life course perspectives augment traditional public health approaches to prevention by emphasizing the importance of unique windows of opportunity for prevention

Abstinence promotion under PEPFAR: The shifting focus of HIV prevention for youth

Abstinence-until-marriage (AUM) – strongly supported by religious conservatives in the U.S. - became a key element of initial HIV prevention efforts under the President’s Emergency Plan for AIDS Relief (PEPFAR). AUM programs have demonstrated limited efficacy in changing behaviors, promoted medically inaccurate information, and withheld life-saving information about risk reduction. A focus on AUM also undermined national efforts in Africa to create integrated youth HIV prevention programs. PEPFAR prevention efforts after 2008 shifted to science-based programming, however vestiges of AUM remain. Primary prevention programs within PEPFAR are essential and nations must be able to design HIV prevention based on local needs and prevention science

Human Papillomavirus Type 16 Variants in Paired Enrollment and Follow-up Cervical Samples: Implications for a Proper Understanding of Type-Specific Persistent Infections

Prospective studies of the persistence of human papilloma-virus (HPV) variants are rare and typically small. We sequenced HPV-16 variants in longitudinal pairs of specimens from 86 women enrolled in the ASCUS-LSIL Triage Study. A change of variants was identified in 4 women (4.7% [95% confidence interval, 1.3%-11.5%]). Among women with intervening HPV results (n = 60), a variant switch occurred in 2 of 11 who had evidence of intervening negativity for HPV-16, compared with 1 of 49 who consistently tested positive (P = .11). These results suggest the possibility that rare misclassification of transient infections as persistent infections occurs in natural history studies of type-specific HPV infections

Mobility among youth in Rakai, Uganda: Trends, characteristics, and associations with behavioural risk factors for HIV

Mobility, including migration and travel, influences risk of HIV. This study examined time trends and characteristics among mobile youth (15–24 years) in rural Uganda, and the relationship between mobility and risk factors for HIV. We used data from an annual household census and population-based cohort study in the Rakai district, Uganda. Data on in-migration and out-migration were collected among youth (15–24 years) from 43 communities from 1999 to 2011 (N = 112,117 observations) and travel among youth residents from 2003 to 2008 (N = 18,318 observations). Migration and travel were more common among young women than young men. One in five youth reported out-migration. Over time, out-migration increased among youth and in-migration remained largely stable. Primary reasons for migration included work, living with friends or family, and marriage. Recent travel within Uganda was common and increased slightly over time in teen women (15–19 years old), and young adult men and women (20–24 years old). Mobile youth were more likely to report HIV-risk behaviours including: alcohol use, sexual experience, multiple partners, and inconsistent condom use. Our findings suggest that among rural Ugandan youth, mobility is increasingly common and associated with HIV-risk factors. Knowledge of patterns and characteristics of a young, high-risk mobile population has important implications for HIV interventions

Factors associated with incident HIV infection versus prevalent infection among youth in Rakai, Uganda

Factors associated with prevalent and incident HIV infection were compared among sexually experienced Ugandans aged 15–24. Most factors were similar. However, in women, older age and current marriage were associated with prevalent, but not incident, infection. It is important to recognize the limitations of prevalence analyses for identifying at-risk youth