Ethnicity, socioeconomic status, transfusions and risk of hepatitis B and hepatitis C infection

This study identifies the risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) and measures the prevalence of hepatitis B surface antigen (HBsAg) and antibody to hepatitis C (anti-HCV) in the general population of Jakarta. A population-based sample of 985 people aged 15 and above was surveyed. Risk factors were identified through questionnaires and home visits. Serum was analysed for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), anti-HCV, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The seroprevalence was: 4.0% (39/985) for HBsAg, 17.2% (170/985) for anti-HBs, and 3.9% (38/985) for anti-HCV. The risk factors for hepatitis B and hepatitis C infection had little in common. Low socioeconomic status was a strong risk factor for HBsAg (adjusted odds ratio (OR) 18.09; 95% confidence interval (CI) 2.35–139.50). In addition, the Chinese group has 2.97 higher risk of having HBV infection compared with the Malayan ethnic group (adjusted OR 2.97; 95% CI 1.22–7.83). There was moderate positive trend between family size and risk of HBsAg positivity ( P = 0.130). Age over 50 (adjusted OR 14.72; 95% CI 4.35–49.89) and history of transfusion were significant risk factors for hepatitis C (adjusted OR 3.03; 95% CI 1.25–7.33). Hepatitis B and hepatitis C infections have different risk factors in Jakarta, a high risk in population for both diseases. Hepatitis B transmission is associated with low socioeconomic status, Chinese ethnic group and large family size, while hepatitis C is associated with an older age and a history of transfusions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72591/1/j.1440-1746.1997.tb00365.x.pd

Towards a pathway definition of Parkinson’s disease: a complex disorder with links to cancer, diabetes and inflammation

We have previously established a first whole genome transcriptomic profile of sporadic Parkinson’s disease (PD). After extensive brain tissue-based validation combined with cycles of iterative data analysis and by focusing on the most comparable cases of the cohort, we have refined our analysis and established a list of 892 highly dysregulated priority genes that are considered to form the core of the diseased Parkinsonian metabolic network. The substantia nigra pathways, now under scrutiny, contain more than 100 genes whose association with PD is known from the literature. Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset. Apart from the complete list of 892 priority genes, we present pathways revealing PD ‘hub’ as well as ‘peripheral’ network genes. The latter include Lewy body components or interact with known PD genes. Biological associations of PD with cancer, diabetes and inflammation are discussed and interactions of the priority genes with several drugs are provided. Our study illustrates the value of rigorous clinico-pathological correlation when analysing high-throughput data to make optimal use of the histopathological phenome, or morphonome which currently serves as the key diagnostic reference for most human diseases. The need for systematic human tissue banking, following the highest possible professional and ethical standard to enable sustainability, becomes evident

The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review

Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with infusion reactions. Concomitant immunomodulators in the form of methotrexate or azathioprine reduced the immunogenicity of therapeutic antibodies in rheumatoid arthritis, Crohn disease, and juvenile idiopathic arthritis. The occurrence of adverse events does not increase when immunomodulators are added to therapeutic antibodies. The mechanism whereby methotrexate and azathioprine influence immunogenicity remains unclear. Evidence-based consensus on prescribing concomitant immunomodulators is needed

DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers

Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours

Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST)

<p>Abstract</p> <p>Background</p> <p>Folic acid (FA) added to foods during fortification is 70-85% bioavailable compared to 50% of folate occurring naturally in foods. Thus, if FA supplements also are taken during pregnancy, both mother and fetus can be exposed to FA exceeding the Institute of Medicine's recommended tolerable upper limit (TUL) of 1,000 micrograms per day (μg/d) for adult pregnant women. The primary objective is to estimate the proportion of women taking folic acid (FA) doses exceeding the TUL before and during pregnancy, and to identify correlates of high FA use.</p> <p>Methods</p> <p>During 2005-2008, pre-pregnancy and pregnancy-related data on dietary supplementation were obtained by interviewing 539 pregnant women enrolled at two obstetrics-care facilities in Durham County, North Carolina.</p> <p>Results</p> <p>Before pregnancy, 51% of women reported FA supplementation and 66% reported this supplementation during pregnancy. Before pregnancy, 11.9% (95% CI = 9.2%-14.6%) of women reported supplementation with FA doses above the TUL of 1,000 μg/day, and a similar proportion reported this intake prenatally. Before pregnancy, Caucasian women were more likely to take FA doses above the TUL (OR = 2.99; 95% = 1.28-7.00), compared to African American women, while women with chronic conditions were less likely to take FA doses above the TUL (OR = 0.48; 95%CI = 0.21-0.97). Compared to African American women, Caucasian women were also more likely to report FA intake in doses exceeding the TUL during pregnancy (OR = 5.09; 95%CI = 2.07-12.49).</p> <p>Conclusions</p> <p>Fifty-one percent of women reported some FA intake before and 66% during pregnancy, respectively, and more than one in ten women took FA supplements in doses that exceeded the TUL. Caucasian women were more likely to report high FA intake. A study is ongoing to identify possible genetic and non-genotoxic effects of these high doses.</p

The effect of a curriculum-based physical activity intervention on accelerometer-assessed physical activity in schoolchildren: a non-randomised mixed methods controlled before-and-after study

Classroom-based physical activity (PA) interventions offer the opportunity to increase PA without disrupting the curriculum. We aimed to explore the feasibility and potential effectiveness of a classroom-based intervention on moderate to vigorous PA (MVPA) and total PA. The secondary aim was to assess the acceptability and sustainability of the intervention. In a mixed-methods, non-randomised, exploratory controlled before-and-after study, 152 children (10 ± 0.7 years) were recruited from five schools; two intervention (n = 72) and three control (n = 80) schools. School teachers delivered an 8-week classroom-based intervention, comprising of 10 minutes daily MVPA integrated into the curriculum. The control schools maintained their usual school routine. Mean daily MVPA (min), total PA (mean cpm), physical fitness, and health-related quality of life measurements were taken at baseline, end of intervention, and 4-weeks post-intervention (follow-up). Data were analysed using a constrained baseline longitudinal analysis model accounting for the hierarchical data structure. For the primary outcomes (MVPA and total PA) the posterior mean difference and 95% compatibility interval were derived using a semi-Bayesian approach with an explicit prior. The acceptability and sustainability of the intervention was explored via thematic content analysis of focus group discussions with teachers (n = 5) and children (n = 50). The difference in mean daily MVPA (intervention-control) was 2.8 (-12.5 to 18.0) min/day at 8 weeks and 7.0 (-8.8 to 22.8) min/day at follow-up. For total PA, the differences were -2 (-127 to 124) cpm at 8-weeks and 11 (-121 to 143) cpm at follow-up. The interval estimates indicate that meaningful mean effects (both positive and negative) as well as trivial effects are reasonably compatible with the data and design. The intervention was received positively with continuation reported by the teachers and children. Classroom-based PA could hold promise for increasing average daily MVPA, but a large cluster randomised controlled trial is required

SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair

The research leading to these results is supported by Cancer Research UK (XYG, RAB, EG, PM, PE, SG, C Santos, AJR, NM, PAB, AS and C Swanton), Breast Cancer Research Foundation (C Swanton and NK), Medical Research Council (ID: G0902275 to MG and C Santos; ID: G0701935/2 to AJR and C Swanton), the Danish Cancer Society (AMM, J Bartkova and J Bartek), the Lundbeck Foundation (R93-A8990 to J Bartek), the Ministry of the interior of the Czech Republic (grant VG20102014001 to MM and J Bartek), the National Program of Sustainability (grant LO1304 to MM and J Bartek), the Danish Council for Independent Research (grant DFF-1331-00262 to J Bartek), NIHR RMH/ICR Biomedical Research Centre for Cancer (JL), the EC Framework 7 (PREDICT 259303 to XYG, EG, PM, MG, TJ and C Swanton; DDResponse 259892 to J Bartek and J Bartkova and RESPONSIFY ID:259303 to C Swanton), UCL Overseas Research Scholarship (SG). C Swanton is also supported by the European Research Council, Rosetrees Trust and The Prostate Cancer Foundation. This research is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre

Illness management and recovery (IMR) in Danish community mental health centres

<p>Abstract</p> <p>Background</p> <p>Schizophrenia and bipolar disorder are severe mental illnesses that can have a significant disabling impact on the lives of people. Psychosocial interventions that stress hope and recovery as a part of a multi-dimensional approach are possibly indicated to support people with severe mental illness in facilitating recovery. Illness Management and Recovery (IMR) is a curriculum-based psychosocial intervention designed as structured program with a recovery-oriented approach. The aim of IMR is to rehabilitate people with severe mental illnesses by helping them acquire knowledge and skills in managing their illness and achieve personal recovery goals. Previous randomised clinical trials indicate that IMR can be implemented with a good effect and a high fidelity though further trials are crucial to demonstrate the potential effectiveness of IMR.</p> <p>Methods/Design</p> <p>The trial design is a randomised, assessor-blinded, multi-centre, clinical trial of the IMR program compared with treatment as usual for 200 participants diagnosed with schizophrenia or bipolar disorder under the care of two community mental health centres in the Capital Region of Denmark. The primary outcome is level of functioning at the end of treatment. The secondary outcomes are disease symptoms; use of alcohol/drugs; individual meaning of recovery; hope; hospital admissions and out-patient psychiatric treatment at the end of treatment and the abovementioned and level of functioning at follow-up 21 months after baseline.</p> <p>Discussion</p> <p>If the results of this trial show IMR to be effective these positive results will strengthen the evidence of IMR as an effective comprehensive psychosocial intervention with a recovery-oriented approach for people with severe mental illness. This will have significant implications for the treatment and recovery of people with severe mental illness.</p> <p>Trial registration</p> <p>Registration number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01361698">NCT01361698</a>.</p

The theory of expanded, extended, and enhanced opportunities for youth physical activity promotion

Background Physical activity interventions targeting children and adolescents (≤18 years) often focus on complex intra- and inter-personal behavioral constructs, social-ecological frameworks, or some combination of both. Recently published meta-analytical reviews and large-scale randomized controlled trials have demonstrated that these intervention approaches have largely produced minimal or no improvements in young people\u27s physical activity levels. Discussion In this paper, we propose that the main reason for previous studies\u27 limited effects is that fundamental mechanisms that lead to change in youth physical activity have often been overlooked or misunderstood. Evidence from observational and experimental studies is presented to support the development of a new theory positing that the primary mechanisms of change in many youth physical activity interventions are approaches that fall into one of the following three categories: (a) the expansion of opportunities for youth to be active by the inclusion of a new occasion to be active, (b) the extension of an existing physical activity opportunity by increasing the amount of time allocated for that opportunity, and/or (c) the enhancement of existing physical activity opportunities through strategies designed to increase physical activity above routine practice. Their application and considerations for intervention design and interpretation are presented. Summary The utility of these mechanisms, referred to as the Theory of Expanded, Extended, and Enhanced Opportunities (TEO), is demonstrated in their parsimony, logical appeal, support with empirical evidence, and the direct and immediate application to numerous settings and contexts. The TEO offers a new way to understand youth physical activity behaviors and provides a common taxonomy by which interventionists can identify appropriate targets for interventions across different settings and contexts. We believe the formalization of the TEO concepts will propel them to the forefront in the design of future intervention studies and through their use, lead to a greater impact on youth activity behaviors than what has been demonstrated in previous studies