Health-related quality of life following a clinical weight loss intervention among overweight and obese adults: intervention and 24 month follow-up effects

BACKGROUND: Despite a growing literature on the efficacy of behavioral weight loss interventions, we still know relatively little about the long terms effects they have on HRQL. Therefore, we conducted a study to investigate the immediate post-intervention (6 months) and long-term (12 and 24 months) effects of clinically based weight management programs on HRQL. METHODS: We conducted a randomized clinical trial in which all participants completed a 6 month clinical weight loss program and were randomized into two 6-month extended care groups. Participants then returned at 12 and 24 months for follow-up assessments. A total of 144 individuals (78% women, M age = 50.2 (9.2) yrs, M BMI = 32.5 (3.8) kg/m(2)) completed the 6 month intervention and 104 returned at 24 months. Primary outcomes of weight and HRQL using the SF-36 were analyzed using multivariate repeated measures analyses. RESULTS: There was complete data on 91 participants through the 24 months of the study. At baseline the participants scored lower than U.S. age-specific population norms for bodily pain, vitality, and mental health. At the completion of the 6 month clinical intervention there were increases in the physical and mental composite measures as well as physical functioning, general health, vitality, and mental health subscales of the SF-36. Despite some weight regain, the improvements in the mental composite scale as well as the physical functioning, vitality, and mental health subscales were maintained at 24 months. There were no significant main effects or interactions by extended care treatment group or weight loss group (whether or not they maintained 5% loss at 24 months). CONCLUSION: A clinical weight management program focused on behavior change was successful in improving several factors of HRQL at the completion of the program and many of those improvements were maintained at 24 months. Maintaining a significant weight loss (> 5%) was not necessary to have and maintain improvements in HRQL

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy

Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult

The endoneurial microenvironment, delimited by the endothelium of endoneurial vessels and a multi-layered ensheathing perineurium, is a specialized milieu intérieur within which axons, associated Schwann cells and other resident cells of peripheral nerves function. The endothelium and perineurium restricts as well as regulates exchange of material between the endoneurial microenvironment and the surrounding extracellular space and thus is more appropriately described as a blood–nerve interface (BNI) rather than a blood–nerve barrier (BNB). Input to and output from the endoneurial microenvironment occurs via blood–nerve exchange and convective endoneurial fluid flow driven by a proximo-distal hydrostatic pressure gradient. The independent regulation of the endothelial and perineurial components of the BNI during development, aging and in response to trauma is consistent with homeostatic regulation of the endoneurial microenvironment. Pathophysiological alterations of the endoneurium in experimental allergic neuritis (EAN), and diabetic and lead neuropathy are considered to be perturbations of endoneurial homeostasis. The interactions of Schwann cells, axons, macrophages, and mast cells via cell–cell and cell–matrix signaling regulate the permeability of this interface. A greater knowledge of the dynamic nature of tight junctions and the factors that induce and/or modulate these key elements of the BNI will increase our understanding of peripheral nerve disorders as well as stimulate the development of therapeutic strategies to treat these disorders

Wellbeing and arthritis incidence:The survey of health, ageing and retirement in Europe

BACKGROUND: A number of studies provide evidence for an association between psychosocial factors and risk of incident arthritis. Current evidence is largely limited to the examination of negative factors such as perceived stress, but positive factors such as subjective wellbeing may also play a role. PURPOSE: The purpose of the current study was to investigate whether people with higher subjective wellbeing have a lower risk of developing arthritis. METHODS: We used Cox proportional hazards regression to examine the prospective relationship between wellbeing (measured using the CASP-12) and incidence of arthritis over a 9-year period. The sample consisted of 13,594 participants aged ≥50 years from the Survey of Health, Ageing and Retirement in Europe. RESULTS: There was a significant association between greater wellbeing and reduced incident arthritis that was stronger at younger ages. In sex-adjusted analyses, for a standard deviation increase in CASP-12 score, the hazard ratios (95 % confidence intervals) for incident arthritis in people aged <65 and ≥65 years were 0.73 (0.69–0.77) and 0.80 (0.77–0.85), respectively. After further adjustment for other established risk factors, these associations were attenuated but remained significant in both age groups: the fully adjusted hazard ratios were 0.82 (0.77–0.87) and 0.88 (0.82–0.95), respectively. CONCLUSIONS: These results provide evidence for an association between greater wellbeing and reduced risk of incident arthritis and, more generally, support the theory that psychosocial factors are implicated in the aetiology of this disease. Future research needs to delineate the mechanisms underlying the association between wellbeing and arthritis risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12160-015-9764-6) contains supplementary material, which is available to authorized users

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe