Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation.

DNA-protein crosslinks (DPCs) arise from enzymatic intermediates, metabolism or chemicals like chemotherapeutics. DPCs are highly cytotoxic as they impede DNA-based processes such as replication, which is counteracted through proteolysis-mediated DPC removal by spartan (SPRTN) or the proteasome. However, whether DPCs affect transcription and how transcription-blocking DPCs are repaired remains largely unknown. Here we show that DPCs severely impede RNA polymerase II-mediated transcription and are preferentially repaired in active genes by transcription-coupled DPC (TC-DPC) repair. TC-DPC repair is initiated by recruiting the transcription-coupled nucleotide excision repair (TC-NER) factors CSB and CSA to DPC-stalled RNA polymerase II. CSA and CSB are indispensable for TC-DPC repair; however, the downstream TC-NER factors UVSSA and XPA are not, a result indicative of a non-canonical TC-NER mechanism. TC-DPC repair functions independently of SPRTN but is mediated by the ubiquitin ligase CRL4CSA and the proteasome. Thus, DPCs in genes are preferentially repaired in a transcription-coupled manner to facilitate unperturbed transcription.

Does provider-initiated HIV testing and counselling lead to higher HIV testing rate and HIV case finding in Rwandan clinics?

BACKGROUND: Provider-initiated HIV testing and counselling (PITC) is promoted as a means to increase HIV case finding. We assessed the effectiveness of PITC to increase HIV testing rate and HIV case finding among outpatients in Rwandan health facilities (HF). METHODS: PITC was introduced in six HFs in 2009-2010. HIV testing rate and case finding were compared between phase 1 (pre-PITC) and phase 3 (PITC period) for outpatient-department (OPD) attendees only, and for OPD and voluntary counseling & testing (VCT) departments combined. RESULTS: Out of 26,367 adult OPD attendees in phase 1, 4.7% were tested and out of 29,864 attendees in phase 3, 17.0% were tested (p < 0.001). The proportion of HIV cases diagnosed was 0.25% (67/26,367) in phase 1 and 0.46% (136/29864) in phase 3 (p < 0.001). In multivariable analysis, both testing rate and case finding were significantly higher in phase 3 for OPD attendees. In phase 1 most of the HIV testing was done in VCT departments rather than at the OPD (78.6% vs 21.4% respectively); in phase 3 this was reversed (40.0% vs 60.0%; p < 0.001). In a combined analysis of VCT and OPD attendees, testing rate increased from 18.7% in phase 1 to 25.4% in phase 3, but case finding did not increase. In multivariable analysis, testing rate was significantly higher in phase 3 (OR 1.67; 95% CI 1.60-1.73), but case finding remained stable (OR 1.09; 95% CI 0.93-1.27). CONCLUSION: PITC led to a shift of HIV testing from VCT department to the OPD, a higher testing rate, but no additional HIV case finding.

Provider-initiated HIV testing and counselling in Rwanda: acceptability among clinic attendees and workers, reasons for testing and predictors of testing.

INTRODUCTION: Routine provider-initiated HIV testing and counselling (PITC) may increase HIV testing rates, but whether PITC is acceptable to health facility (HF) attendees is unclear. In the course of a PITC intervention study in Rwanda, we assessed the acceptability of PITC, reasons for being or not being tested and factors associated with HIV testing. METHODS: Attendees were systematically interviewed in March 2009 as they left the HF, regarding knowledge and acceptability of PITC, history of testing and reasons for being tested or not. Subsequently, PITC was introduced in 6 of the 8 HFs and a second round of interviews was conducted. Independent factors associated with testing were analysed using logistic regression. Randomly selected health care workers (HCWs) were also interviewed. RESULTS: 1772 attendees were interviewed. Over 95% agreed with the PITC policy, both prior to and after implementation of PITC policy. The most common reasons for testing were the desire to know one's HIV status and having been offered an HIV test by an HCW. The most frequent reasons for not being tested were known HIV status and test not being offered. In multivariable analysis, PITC, age ≥15 years, and not having been previously tested were factors significantly associated with testing. Although workload was increased by PITC, HIV testing rates increased and HCWs overwhelmingly supported the policy. CONCLUSION: Among attendees and HCWs in Rwandan clinics, the acceptability of PITC was very high. PITC appeared to increase testing rates and may be helpful in prevention and early access to treatment.

Condom use, risk perception, and HIV knowledge: a comparison across sexes in Nigeria.

BACKGROUND: This paper analyzes how different types of Human immunodeficiency virus (HIV) knowledge influences condom use across the sexes. METHODS: The empirical work was based on a household survey conducted among 1979 households of a representative group of stallholders in Lagos, Nigeria in 2008. Condom use during last sexual intercourse was analyzed using a multivariate model corrected for clustering effects. The data included questions on socioeconomic characteristics, knowledge of the existence of HIV, HIV prevention, HIV stigma, intended pregnancy, and risk perceptions of engaging in unprotected sex. RESULTS: A large HIV knowledge gap between males and females was observed. Across the sexes, different types of knowledge are important in condom use. Low-risk perceptions of engaging in unprotected sex and not knowing that condoms prevent HIV infection appear to be the best predictors for risky sexual behavior among men. For females, stigma leads to lower condom use. Obviously, lack of knowledge on where condoms are available (9.4% and 29.1% of male and female respondents, respectively) reduced condom use in both males and females. CONCLUSION: The results call for programmatic approaches to differentiate between males and females in the focus of HIV prevention campaigns. Moreover, the high predictive power of high-risk perceptions of engaging in unprotected sex (while correcting for other HIV knowledge indicators) calls for further exploration on how to influence these risk perceptions in HIV prevention programs.

Hypertension in sub-Saharan Africa: cross-sectional surveys in four rural and urban communities.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of adult mortality in low-income countries but data on the prevalence of cardiovascular risk factors such as hypertension are scarce, especially in sub-Saharan Africa (SSA). This study aims to assess the prevalence of hypertension and determinants of blood pressure in four SSA populations in rural Nigeria and Kenya, and urban Namibia and Tanzania. METHODS AND FINDINGS: We performed four cross-sectional household surveys in Kwara State, Nigeria; Nandi district, Kenya; Dar es Salaam, Tanzania and Greater Windhoek, Namibia, between 2009-2011. Representative population-based samples were drawn in Nigeria and Namibia. The Kenya and Tanzania study populations consisted of specific target groups. Within a final sample size of 5,500 households, 9,857 non-pregnant adults were eligible for analysis on hypertension. Of those, 7,568 respondents ≥ 18 years were included. The primary outcome measure was the prevalence of hypertension in each of the populations under study. The age-standardized prevalence of hypertension was 19.3% (95%CI:17.3-21.3) in rural Nigeria, 21.4% (19.8-23.0) in rural Kenya, 23.7% (21.3-26.2) in urban Tanzania, and 38.0% (35.9-40.1) in urban Namibia. In individuals with hypertension, the proportion of grade 2 (≥ 160/100 mmHg) or grade 3 hypertension (≥ 180/110 mmHg) ranged from 29.2% (Namibia) to 43.3% (Nigeria). Control of hypertension ranged from 2.6% in Kenya to 17.8% in Namibia. Obesity prevalence (BMI ≥ 30) ranged from 6.1% (Nigeria) to 17.4% (Tanzania) and together with age and gender, BMI independently predicted blood pressure level in all study populations. Diabetes prevalence ranged from 2.1% (Namibia) to 3.7% (Tanzania). CONCLUSION: Hypertension was the most frequently observed risk factor for CVD in both urban and rural communities in SSA and will contribute to the growing burden of CVD in SSA. Low levels of control of hypertension are alarming. Strengthening of health care systems in SSA to contain the emerging epidemic of CVD is urgently needed.