The reversed social gradient: higher breast cancer mortality in the higher educated compared to lower educated. A comparison of 11 European populations during the 1990s

Higher socioeconomic position has been reported to be associated with increased risk of breast cancer mortality. Our aim was to see if this is consistently observed within 11 European populations in the 1990s. Longitudinal data on breast cancer mortality by educational level and marital status were obtained for Finland, Norway, Denmark, England and Wales, Belgium, France, Switzerland, Austria, Turin, Barcelona and Madrid. The relationship between breast cancer mortality and education was summarised by means of the relative index of inequality. A positive association was found in all populations, except for Finland, France and Barcelona. Overall, women with a higher educational level had approximately 15% greater risk of dying from breast cancer than those with lower education. This was observed both among never- and ever-married women. The greater risk of breast cancer mortality among women with a higher level of education was a persistent and generalised phenomenon in Europe in the 1990s.     

Sexual risk factors associated with volunteering for HIV vaccine research in South Africa

There are few data on how the risk profiles of individuals who volunteer for HIV vaccine research compare to the general population from which participants are recruited. This study contrasts demographic and sexual risk behaviours among volunteers in an HIV vaccine preparedness cohort with data from a cross-sectional community survey conducted in the same peri-urban community during the same time period. For the HIV vaccine preparedness cohort, structured questionnaires were administered to 140 HIV-negative individuals aged between 16 and 40 years. A questionnaire with identical measures was self-administered in a cross-sectional community survey of 583 randomly selected individuals within the same age range. Compared to the local community sample, individuals who volunteered for the HIV vaccine preparedness cohort were younger (adjusted odds ratio = 0.48; 95% CI = 0.28-0.82), more likely to have had a sexually transmitted disease (adjusted odds ratio = 1.75; 95% CI = 1.03-2.99) and less likely to use condoms (adjusted odds ratio = 0.51; 95% CI = 0.3-0.86). Cohort participants were also more likely to perceive themselves and their partners to be at risk of HIV infection, though these associations did not persist in multivariate analysis. These findings suggest that volunteers for vaccine-related research may be at greater risk of HIV infection than the general population from which they are recruited.     

Willingness to participate in HIV vaccine research in a peri-urban South African community

Research on willingness to participate in HIV vaccine trials is important in preparations for HIV vaccine research, but there are few data from sub-Saharan Africa. We interviewed 198 individuals in a peri-urban South African community immediately after enrolment into an HIV vaccine preparedness study on their willingness to participate in hypothetical vaccine trials. Overall 23% of participants (n = 46) said that they would be willing to participate in an HIV vaccine trial. Willingness was associated with increasing age, male gender, and increasing knowledge about vaccines generally and HIV vaccines specifically. In multivariate analysis, a 1-unit increase in HIV vaccine knowledge score was associated with a 10-fold increase in willingness to participate (adjusted odds ratio, 10.72, 95% confidence intervals: 4.40-26.12). These results suggest that while willingness to participate in HIV vaccine trials is relatively low in this setting, educational campaigns may have a substantial impact on individuals' willingness to participate in research.     

Atomic structure and nonhomologous end-joining function of the polymerase component of bacterial DNA ligase D

DNA ligase D (LigD) is a large polyfunctional protein that participates in a recently discovered pathway of nonhomologous end-joining in bacteria. LigD consists of an ATP-dependent ligase domain fused to a polymerase domain (Pol) and a phosphoesterase module. The Pol activity is remarkable for its dependence on manganese, its ability to perform templated and nontemplated primer extension reactions, and its preference for adding ribonucleotides to blunt DNA ends. Here we report the 1.5-A crystal structure of the Pol domain of Pseudomonas LigD and its complexes with manganese and ATP/dATP substrates, which reveal a minimized polymerase with a two-metal mechanism and a fold similar to that of archaeal DNA primase. Mutational analysis highlights the functionally relevant atomic contacts in the active site. Although distinct nucleoside conformations and contacts for ATP versus dATP are observed in the cocrystals, the functional analysis suggests that the ATP-binding mode is the productive conformation for dNMP and rNMP incorporation. We find that a mutation of Mycobacterium LigD that uniquely ablates the polymerase activity results in increased fidelity of blunt-end double-strand break repair in vivo by virtue of eliminating nucleotide insertions at the recombination junctions. Thus, LigD Pol is a direct catalyst of mutagenic nonhomologous end-joining in vivo. Our studies underscore a previously uncharacterized role for the primase-like polymerase family in DNA repair.     

TB patients' perspectives on integrated TB/HIV services in South Africa

There are few data describing patients' attitudes towards the integration of antiretroviral therapy for HIV-infected patients into existing TB services. We investigated this issue among patients receiving TB treatment at a primary care facility in Cape Town, South Africa. Of 85 patients interviewed, the vast majority (92%, n = 78) stated they would be willing to attend an integrated TB/HIV service; perceived stigmatization of TB and HIV was a significant predictor of negative attitudes towards a combined TB/HIV programme (adjusted odds ratio, 19.90, P = 0.02). While integrated TB/HIV services appear generally acceptable in this setting, continuing efforts to combat stigmatization are necessary to ensure maximum uptake.     

Cholangiocyte bile salt transporters in cholesterol gallstone-susceptible and resistant inbred mouse strains

Background and Aim: We investigated the dietary and gender influences on the expression and functionality of cholangiocyte bile salt transporters and development of biliary hyperplasia in cholesterol gallstone‐susceptible C57L/J and resistant AKR/J mice. Methods: C57L and AKR mice were fed chow, a lithogenic diet, or a cholic acid‐containing diet for 14 days. Expression of cholangiocyte bile salt transporter proteins ASBT (SLC10A2), ILBP (FABP6), and MRP3 (ABCC3) were studied by Western blot analysis. Taurocholate uptake studies were performed using microperfusion of isolated bile duct units. The pre‐ and post‐perfusion taurocholate concentrations were analyzed by high performance liquid chromatography. Biliary proliferation in liver sections was scored. Results: The lithogenic diet induced ductular proliferation in C57L mice. On chow, SLC10A2 and ABCC3 were overexpressed in male and female C57L compared to AKR mice. A lithogenic diet reduced the expressions of FABP6 in both male and female C57L mice, SLC10A2 in female C57L mice, and ABCC3 in male C57L mice. These alterations in transporter expressions were not associated with changes in taurocholate uptake. The lithogenic diet induced biliary hyperplasia and reduced bile salt transporter expressions in C57L mice. Conclusions: Although bile salt uptake was not increased in the bile duct unit, we speculate that the biliary hyperplasia on the lithogenic diet may lead to an increase in intrahepatic bile salt recycling during cholesterol cholelithogenesis.     

Activity-adjusted 24-hour ambulatory blood pressure and cardiac remodeling in children with sleep disordered breathing

Questions remain as to whether pediatric sleep disordered breathing increases the risk for elevated blood pressure and blood pressure-dependent cardiac remodeling. We tested the hypothesis that activity-adjusted morning blood pressure surge, blood pressure load, and diurnal and nocturnal blood pressure are significantly higher in children with sleep disordered breathing than in healthy controls and that these blood pressure parameters relate to left ventricular remodeling. 24-hour ambulatory blood pressure parameters were compared between groups. The associations between blood pressure and left ventricular relative wall thickness and mass were measured. 140 children met the inclusion criteria. In children with apnea hypopnea index <5 per hour, a significant difference from controls was the morning blood surge. Significant increases in blood pressure surge, blood pressure load, and in 24-hour ambulatory blood pressure were evident in those whom the apnea hypopnea index exceeded 5 per hour. Sleep disordered breathing and body mass index had similar effect on blood pressure parameters except for nocturnal diastolic blood pressure, where sleep disordered breathing had a significantly greater effect than body mass index. Diurnal and nocturnal systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure predicted the changes in left ventricular relative wall thickness. Therefore, sleep disordered breathing in children who are otherwise healthy is independently associated with an increase in morning blood pressure surge, blood pressure load, and 24-hour ambulatory blood pressure. The association between left ventricular remodeling and 24-hour blood pressure highlights the role of sleep disordered breathing in increasing cardiovascular morbidity.     

Preventing human immunodeficiency virus infection among sexual assault survivors in Cape Town, South Africa: an observational study

We describe 131 South African sexual assault survivors offered HIV post-exposure prophylaxis (PEP). While the median days completed was 27 (IQR 27, 28), 34% stopped PEP or missed doses. Controlling for baseline symptoms, PEP was not associated with symptoms (OR = 1.30, 95% CI = 0.66, 2.64). Factors associated with unprotected sex included prior unprotected sex (OR = 6.46, 95% CI = 3.04, 13.74), time since the assault (OR = 1.33, 95% CI = 1.12, 1.57) and age (OR = 1.30, 95% CI = 1.08, 1.57). Trauma counseling was protective (OR = 0.18, 95% CI = 0.05, 0.58). Four instances of seroconversion were observed by 6 months (risk = 3.7%, 95% CI = 1.0, 9.1). Proactive follow-up is necessary to increase the likelihood of PEP completion and address the mental health and HIV risk needs of survivors. Adherence interventions and targeted risk reduction counseling should be provided to minimize HIV acquisition.     

Human and pet-related risk factors for household evacuation failure during a natural disaster

This study characterized risk factors for household evacuation failure. A random digit dial telephone survey was conducted of 397 households in Yuba County, California, in July 1997, 6 months after residents had been under evacuation notice due to flooding. Case households failed to evacuate, whereas control households evacuated. The cumulative incidence of household evacuation failure was 19.4%. Fewer households with children (25.8%) failed to evacuate than households without children (45.9%, p < 0.01). More households with pets (20.9%) than households without pets failed to evacuate (16.3%, p = 0.11). With multivariate logistic regression, the risk of household evacuation failure was lower in households with children (odds ratio = 0.4, 95% confidence interval: 0.2, 0.8) compared with households without children. The risk of household evacuation failure increased in pet-owning households without children (odds ratio = 1.3, 95% confidence interval: 1.1, 1.5) compared with pet-owning households with children; the more pets a household owned, the higher the risk of household evacuation failure was. Impediments to pet evacuation, including owning multiple pets, owning outdoor dogs, or not having a cat carrier, explained why many households that owned pets failed to evacuate. Predisaster planning should place a high priority on facilitating pet evacuation through predisaster education of pet owners and emergency management personnel.