Studies in animals have shown that the frequency of urination is inversely associated with the level of potential carcinogens in the urothelium. In humans, an increase in total fluid intake may reduce contact time between carcinogens and urothelium by diluting urinary metabolites and increasing the frequency of voiding. The data on fluid intake in relation to the risk of bladder cancer are inconclusive.
The standard two-stage approach for estimating non-linear dose-response curves based on aggregated data typically excludes those studies with less than three exposure groups. We develop the one-stage method as a linear mixed model and present the main aspects of the methodology, including model specification, estimation, testing, prediction, goodness-of-fit, model comparison, and quantification of between-studies heterogeneity. Using both fictitious and real data from a published meta-analysis, we illustrated the main features of the proposed methodology and compared it to a traditional two-stage analysis. In a one-stage approach, the pooled curve and estimates of the between-studies heterogeneity are based on the whole set of studies without any exclusion. Thus, even complex curves (splines, spike at zero exposure) defined by several parameters can be estimated. We showed how the one-stage method may facilitate several applications, in particular quantification of heterogeneity over the exposure range, prediction of marginal and conditional curves, and comparison of alternative models. The one-stage method for meta-analysis of non-linear curves is implemented in the dosresmeta R package. It is particularly suited for dose-response meta-analyses of aggregated where the complexity of the research question is better addressed by including all the studies.
Retention on antiretroviral therapy (ART) is critical for the successful adoption of the test and treat policy by sub-Saharan African countries, and for realizing the United Nations programme on HIV and AIDS target of 90-90-90. This qualitative study explores HIV positive clients' reasons for discontinuing ART under the MaxART test and treat implementation study in Swaziland.Clients identified as lost to follow-up (LTFU) in the programme database, who had initiated ART under the intervention arm of the MaxART study, were purposively selected from two facilities. LTFU was defined as stopping ART refill for three months or longer from the date of last appointment, and not being classified as transferred out or deceased. Semi-structured face-to-face interviews were conducted with nine clients and one treatment supporter between July and August 2017. All interviews were conducted in the local language, audio-recorded, summarized or transcribed and translated to English for thematic analysis.Respondents described mobility as the first step in a chain of events that affected retention in care. It was entwined with precarious employment, care delivery, interactions with health workers, lack of social support, anticipated stigma and ART-related side-effects, including the exacerbation of hunger. The chains of events involved several intersecting reasons that occurred one after the other as a series of contiguous and linked events that led to clients' eventual discontinuation of ART. The individual accounts of step-by-step decision-making revealed the influence of multi-layered contexts and the importance of critical life-events.Clients' reasons for abandoning ART are a complex, inextricably interwoven chain of events rather than a single occurrence. Mobility is often the first step in the process and commonly results from precarious economic and social circumstances. Currently the health system poorly caters to the reality of people's mobile lives. Interventions should seek to increase healthcare workers' understanding of the chain of events leading up to discontinuation on ART and the social dilemmas that clients face.
We sought to estimate the association between intimate partner violence, a prevalent psychosocial stressor, and the incidence of type 2 diabetes in women.In 2001, 68,376 Nurses' Health Study II participants answered questions on physical, sexual, and psychological intimate partner violence in adulthood (age ≥18 years) and reported the years in which any abuse occurred. We used Cox proportional hazards models to estimate the associations between intimate partner violence exposures and incidence of type 2 diabetes from 2001 to 2007. We also estimated effects of duration and time since intimate partner violence on type 2 diabetes incidence.Of 68,376 respondents, 64,732 met inclusion criteria at the 2001 baseline; of these, 23% reported lifetime physical intimate partner violence, 11% reported lifetime sexual intimate partner violence, and 8% reported moderate and <2% reported severe psychological intimate partner violence. Hazard ratios (HRs) and 95% CIs for type 2 diabetes, adjusted for potential confounders, were 1.18 (1.00-1.39) and 1.08 (0.86-1.35) for more than one lifetime episode of physical and sexual intimate partner violence, respectively, and 1.78 (1.21-2.61) for severe psychological abuse. Addition of updated BMI and other diabetes risk factors reduced the physical intimate partner violence HR to 1.12 (0.94-1.33) and the psychological intimate partner violence HR to 1.61 (1.09-2.38).Physical intimate partner violence is modestly associated with incidence of type 2 diabetes in this population. Severe psychological violence may substantially increase type 2 diabetes risk.
<div>Abstract<p><b>Purpose:</b> DNA methyltransferase-3B (<i>DNMT3B</i>) plays an important role in <i>de novo</i> CpG island methylation. Dnmt3b can induce colon tumor in mice with methylation in specific CpG islands. We hypothesized that cellular DNMT3B level might influence the occurrence of widespread CpG island methylation (i.e., the CpG island methylator phenotype, CIMP) in colon cancer.</p><p><b>Experimental Design:</b> Utilizing 765 colorectal cancers in two cohort studies, we detected DNMT3B expression in 116 (15%) tumors by immunohistochemistry. We assessed microsatellite instability, quantified DNA methylation in repetitive long interspersed nucleotide element-1 (LINE-1) by Pyrosequencing, eight CIMP-specific promoters [<i>CACNA1G, CDKN2A</i> (p16), <i>CRABP1, IGF2, MLH1, NEUROG1, RUNX3</i>, and <i>SOCS1</i>], and eight other CpG islands (<i>CHFR, HIC1, IGFBP3, MGMT</i>, MINT1, MINT31, p14, and <i>WRN</i>) by real-time PCR (MethyLight).</p><p><b>Results:</b> Tumoral DNMT3B overexpression was significantly associated with CIMP-high [≥6/8 methylated CIMP-specific promoters; odds ratio (OR), 3.34; 95% confidence interval, 2.11-5.29; <i>P</i> < 0.0001]. The relations between DNMT3B and methylation in 16 individual CpG islands varied substantially (OR, 0.80-2.96), suggesting variable locus-to-locus specificities of DNMT3B activity. DNMT3B expression was not significantly related with LINE-1 hypomethylation. In multivariate logistic regression, the significant relation between DNMT3B and CIMP-high persisted (OR, 2.39; 95% confidence interval, 1.11-5.14; <i>P</i> = 0.026) after adjusting for clinical and other molecular features, including p53, β-catenin, LINE-1, microsatellite instability, <i>KRAS, PIK3CA</i>, and <i>BRAF</i>. DNMT3B expression was unrelated with patient outcome, survival, or prognosis.</p><p><b>Conclusions:</b> Tumoral DNMT3B overexpression is associated with CIMP-high in colorectal cancer. Our data support a possible role of DNMT3B in nonrandom <i>de novo</i> CpG island methylation leading to colorectal cancer.</p></div>
Abstract Objective: At issue is whether weight loss in HIV infection is a cachectic process, characterised by loss of lean body mass with conservation of fat, or a process of starvation. We present data on body composition from 516 persons at different stages of HIV infection as determined by CD4 counts. Design: Cross-sectional analyses of body composition in relation to CD4 count. Setting: The baseline data from a prospective cohort study of outcomes in HIV/AIDS in relation to nutritional status in Boston, Massachusetts, USA. Subjects: The first 516 subjects with HIV/AIDS to enrol in the study. Results: Differences in weight in relation to CD4 counts were present only at CD4 counts of 600 or less (slope below CD4=600 : 1.9 kg per 100 CD4 cells, P<0.0001). On average, 68% of the difference in weight over CD4 counts was fat (slope: 1.3 kg fat per 100 CD4 cells, P<0.0001 ). Conclusions: This cross-sectional analysis suggests that weight loss consists principally of fat loss in those persons with adequate fat stores. This observation will need to be confirmed in longitudinal analyses.
Objectives: To study consumer acceptance of unmilled brown and undermilled rice among urban south Indians. Methods: Overweight and normal weight adults living in slum and nonslum residences in Chennai participated (n = 82). Bapatla (BPT) and Uma (red pigmented) rice varieties were chosen. These rice varieties were dehusked (unmilled, 0% polish) and further milled to 2.3% and 4.4% polishing (undermilled). Thus, 9 rice samples in both raw and parboiled forms were provided for consumer tasting over a period of 3 days. A 7-point hedonic scale was used to rate consumer preferences. A validated questionnaire was used to collect demographic, anthropometric, medical history, physical activity, dietary intake data, and willingness of the consumers to switch over to brown rice. Results: Consumers reported that the color, appearance, texture, taste, and overall quality of the 4.4% polished rice was strongly preferred in both varieties and forms. Ratings for 0% polished (brown rice) were substantially lower than those of 2.3% polished rice, which were intermediate in ratings between 0% and 4.4% polishing. However, most of the consumers (93%) expressed a willingness to substitute brown or 2.3% polished rice, if affordable, after the taste tests and education on nutritional and health benefits of whole grains. Conclusion: Though most consumers preferred polished white rice, education regarding health benefits may help this population switch to brown or undermilled rice. Cooking quality and appearance of the grains were perceived as the most important factors to consider when purchasing rice among Chennai urban adults.
