Primary group size, social support, gender and future mental health status in a prospective study of people living in private households throughout Great Britain

Background. Structural characteristics of social networks such as primary group size have received less attention than measures of perceived social support. Previous research suggests that associations between social network size and later common mental disorder status may differ according to sex and initial mental state. Method. Adults participating in the 2000 British National Household Survey of psychiatric morbidity were randomly selected for follow-up 18 months later. The revised Clinical Interview Schedule (CIS-R) and the Interview Measure of Social Relations (IMSR) were administered at baseline and follow-up. Primary group size was defined as the total number of close relatives and friends. A four-level scale of common mental disorder was modelled with ordinal logistic regression, based on weighted data (n=2413). Findings. After adjusting for confounders, a primary group size of three or less at time 1 predicted worse mental health at time 2. This effect was greatest in men who were initially non-cases at baseline (averaged odds 4.5) and in women who were initially cases at baseline (average odds 2.9). Primary group size at time 2 was significantly predicted by level of common mental disorder at time 1 in women but not in men. Thus, confounding by baseline disorder does not explain risk of developing poor mental health in socially isolated men. Conclusion. This study replicates the strong effects of primary group size on future mental health that emerge when men and women are studied separately and when subjects are categorized according to baseline mental health status

The population impact of common mental disorders and long-term physical conditions on disability and hospital admission

Background: Long-term physical conditions (LTCs) consume the largest share of healthcare budgets. Although common mental disorders (CMDs) and LTCs often co-occur, the potential impact of improved mental health treatment on severe disability and hospital admissions for physical health problems remains unknown. Method: A cross-sectional study of 7403 adults aged 16–95 years living in private households in England was performed. LTCs were ascertained by prompted self-report. CMDs were ascertained by structured clinical interview. Disability was assessed using questions about problems with activities of daily living. Population impact and potential preventive gain were estimated using population-attributable fraction (PAF), and conservative estimates were obtained using ‘treated non-cases’ as the reference group. Results: Of the respondents, 20.7% reported at least one LTC. The prevalence of CMDs increased with the number of LTCs, but over two-thirds (71.2%) of CMD cases in people with LTCs were untreated. Statistically significant PAFs were found for CMDs and recent hospital admission [13.5%, 95% confidence intervals (CI) 6.6–20.0] and severe disability (31.3%, 95% CI 27.1–35.2) after adjusting for LTCs and other confounders. Only the latter remained significant when using the most conservative estimate of PAF (21.8%, 95% CI 14.0–28.9), and this was reduced only slightly when considering only participants with LTCs (18.5%, 95% CI 7.9–27.9). Conclusions: Better treatments for CMDs in people with LTCs could achieve almost the same population health gain in terms of reducing severe disability as those targeted at the entire population. Interventions to reduce the prevalence of CMDs among people with LTCs should be part of routine medical care

Debt income and mental disorder in the general population

Background The association between poor mental health and poverty is well known but its mechanism is not fully understood. This study tests the hypothesis that the association between low income and mental disorder is mediated by debt and its attendant financial hardship. Method The study is a cross-sectional nationally representative survey of private households in England, Scotland and Wales, which assessed 8580 participants aged 16–74 years living in general households. Psychosis, neurosis, alcohol abuse and drug abuse were identified by the Clinical Interview Schedule – Revised, the Schedule for Assessment in Neuropsychiatry (SCAN), the Alcohol Use Disorder Identification Test (AUDIT) and other measures. Detailed questions were asked about income, debt and financial hardship. Results Those with low income were more likely to have mental disorder [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.68–2.59] but this relationship was attenuated after adjustment for debt (OR 1.58, 95% CI 1.25–1.97) and vanished when other sociodemographic variables were also controlled (OR 1.07, 95% CI 0.77–1.48). Of those with mental disorder, 23% were in debt (compared with 8% of those without disorder), and 10% had had a utility disconnected (compared with 3%). The more debts people had, the more likely they were to have some form of mental disorder, even after adjustment for income and other sociodemographic variables. People with six or more separate debts had a six-fold increase in mental disorder after adjustment for income (OR 6.0, 95% CI 3.5–10.3). Conclusions Both low income and debt are associated with mental illness, but the effect of income appears to be mediated largely by debt

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)

SRAdb: query and use public next-generation sequencing data from within R

Abstract Background The Sequence Read Archive (SRA) is the largest public repository of sequencing data from the next generation of sequencing platforms including Illumina (Genome Analyzer, HiSeq, MiSeq, .etc), Roche 454 GS System, Applied Biosystems SOLiD System, Helicos Heliscope, PacBio RS, and others. Results SRAdb is an attempt to make queries of the metadata associated with SRA submission, study, sample, experiment and run more robust and precise, and make access to sequencing data in the SRA easier. We have parsed all the SRA metadata into a SQLite database that is routinely updated and can be easily distributed. The SRAdb R/Bioconductor package then utilizes this SQLite database for querying and accessing metadata. Full text search functionality makes querying metadata very flexible and powerful. Fastq files associated with query results can be downloaded easily for local analysis. The package also includes an interface from R to a popular genome browser, the Integrated Genomics Viewer. Conclusions SRAdb Bioconductor package provides a convenient and integrated framework to query and access SRA metadata quickly and powerfully from within R.</p

Cyclic strain upregulates VEGF and attenuates proliferation of vascular smooth muscle cells

OBJECTIVE:Vascular smooth muscle cell (VSMC) hypertrophy and proliferation occur in response to strain-induced local and systemic inflammatory cytokines and growth factors which may contribute to hypertension, atherosclerosis, and restenosis. We hypothesize VSMC strain, modeling normotensive arterial pressure waveforms in vitro, results in attenuated proliferative and increased hypertrophic responses 48 hrs post-strain.METHODS:Using Flexcell Bioflex Systems we determined the morphological, hyperplastic and hypertrophic responses of non-strained and biomechanically strained cultured rat A7R5 VSMC. We measured secretion of nitric oxide, key cytokine/growth factors and intracellular mediators involved in VSMC proliferation via fluorescence spectroscopy and protein microarrays. We also investigated the potential roles of VEGF on VSMC strain-induced proliferation.RESULTS:Protein microarrays revealed significant increases in VEGF secretion in response to 18 hours mechanical strain, a result that ELISA data corroborated. Apoptosis-inducing nitric oxide (NO) levels also increased 43% 48 hrs post-strain. Non-strained cells incubated with exogenous VEGF did not reproduce the antimitogenic effect. However, anti-VEGF reversed the antimitogenic effect of mechanical strain. Antibody microarrays of strained VSMC lysates revealed MEK1, MEK2, phospo-MEK1T385, T291, T298, phospho-Erk1/2T202+Y204/T185+T187, and PKC isoforms expression were universally increased, suggesting a proliferative/inflammatory signaling state. Conversely, VSMC strain decreased expression levels of Cdk1, Cdk2, Cdk4, and Cdk6 by 25-50% suggesting a partially inhibited proliferative signaling cascade.CONCLUSIONS:Subjecting VSMC to cyclic biomechanical strain in vitro promotes cell hypertrophy while attenuating cellular proliferation. We also report an upregulation of MEK and ERK activation suggestive of a proliferative phenotype. Hhowever, the proliferative response appears to be aborogated by enhanced antimitogenic cytokine VEGF, NO secretion and downregulation of Cdk expression. Although exogenous VEGF alone is not sufficient to promote the quiescent VSMC phenotype, we provide evidence suggesting that strain is a necessary component to induce VSMC response to the antimitogenic effects of VEGF. Taken together these data indicate that VEGF plays a critical role in mechanical strain-induced VSMC proliferation and vessel wall remodeling. Whether VEGF and/or NO inhibit signaling distal to Erk 1/2 is currently under investigation.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Molecular Characterization of Putative Chordoma Cell Lines

Immortal tumor cell lines are an important model system for cancer research, however, misidentification and cross-contamination of cell lines are a common problem. Seven chordoma cell lines are reported in the literature, but none has been characterized in detail. We analyzed gene expression patterns and genomic copy number variations in five putative chordoma cell lines (U-CH1, CCL3, CCL4, GB60, and CM319). We also created a new chordoma cell line, U-CH2, and provided genotypes for cell lines for identity confirmation. Our analyses revealed that CCL3, CCL4, and GB60 are not chordoma cell lines, and that CM319 is a cancer cell line possibly derived from chordoma, but lacking expression of key chordoma biomarkers. U-CH1 and U-CH2 both have gene expression profiles, copy number aberrations, and morphology consistent with chordoma tumors. These cell lines also harbor genetic changes, such as loss of p16, MTAP, or PTEN, that make them potentially useful models for studying mechanisms of chordoma pathogenesis and for evaluating targeted therapies

Economics of Malaria Prevention in US Travelers to West Africa

Background. Pretravel health consultations help international travelers manage travel-related illness risks through education, vaccination, and medication. This study evaluated costs and benefits of that portion of the health consultation associated with malaria prevention provided to US travelers bound for West Africa. Methods. The estimated change in disease risk and associated costs and benefits resulting from traveler adherence to malaria chemoprophylaxis were calculated from 2 perspectives: the healthcare payer's and the traveler's. We used data from the Global TravEpiNet network of US travel clinics that collect de-identified pretravel data for international travelers. Disease risk and chemoprophylaxis effectiveness were estimated from published medical reports. Direct medical costs were obtained from the Nationwide Inpatient Sample and published literature. Results. We analyzed 1029 records from January 2009 to January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations saved healthcare payers a per-traveler average of $14 (9-day trip) to$372 (30-day trip). For travelers, consultations resulted in a range of net cost of $20 (9-day trip) to a net savings of$32 (30-day trip). Differences were mostly driven by risk of malaria in the destination country. Conclusions. Our model suggests that healthcare payers save money for short- and longer-term trips, and that travelers save money for longer trips when travelers adhere to malaria recommendations and prophylactic regimens in West Africa. This is a potential incentive to healthcare payers to offer consistent pretravel preventive care to travelers. This financial benefit complements the medical benefit of reducing the risk of malaria

Prevalence of psychosis in black ethnic minorities in Britain: analysis based on three national surveys

Purpose A considerable excess of psychosis in black ethnic minorities is apparent from clinical studies, in Britain, as in other developed economies with white majority populations. This excess is not so marked in population surveys. Equitable health service provision should be informed by the best estimates of the excess. We used national survey data to establish the difference in the prevalence of psychosis between black ethnic groups and the white majority in the British general population. Methods Analysis of the combined datasets (N = 26,091) from the British national mental health surveys of 1993, 2000 and 2007. Cases of psychosis were determined either by the use of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), or from a combination of screening items. We controlled for sex, age, social class, unemployment, design features and other putative confounders, using a Disease Risk Score. Results People from black ethnic minorities had an excess prevalence rate of psychosis compared with the white majority population. The OR, weighted for study design and response rate, was 2.72 (95 % CI 1.3–5.6, p = 0.002). This was marginally increased after controlling for potential confounders (OR = 2.90, 95 % CI 1.4–6.2, p = 0.006). Conclusions The excess of psychosis in black ethnic minority groups was similar to that in two previous British community surveys, and less than that based on clinical studies. Even so it confirms a considerable need for increased mental health service resources in areas with high proportions of black ethnic minority inhabitants