A bi-directional relationship between obesity and health-related quality of life : evidence from the longitudinal AusDiab study

Objective: To assess the prospective relationship between obesity and health-related quality of life, including a novel assessment of the impact of health-related quality of life on weight gain.Design and setting: Longitudinal, national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, with surveys conducted in 1999/2000 and 2004/2005.Participants: A total of 5985 men and women aged 25 years at study entry.Main outcome measure(s): At both time points, height, weight and waist circumference were measured and self-report data on health-related quality of life from the SF-36 questionnaire were obtained. Cross-sectional and bi-directional, prospective associations between obesity categories and health-related quality of life were assessed.Results: Higher body mass index (BMI) at baseline was associated with deterioration in health-related quality of life over 5 years for seven of the eight health-related quality of life domains in women (all P0.01, with the exception of mental health, P&gt;0.05), and six out of eight in men (all P&lt;0.05, with the exception of role-emotional, P=0.055, and mental health, P&gt;0.05). Each of the quality-of-life domains related to mental health as well as the mental component summary were inversely associated with BMI change (all P&lt;0.0001 for women and P0.01 for men), with the exception of vitality, which was significant in women only (P=0.008). For the physical domains, change in BMI was inversely associated with baseline general health in women only (P=0.023).Conclusions: Obesity was associated with a deterioration in health-related quality of life (including both physical and mental health domains) in this cohort of Australian adults followed over 5 years. Health-related quality of life was also a predictor of weight gain over 5 years, indicating a bi-directional association between obesity and health-related quality of life. The identification of those with poor health-related quality of life may be important in assessing the risk of future weight gain, and a focus on health-related quality of life may be beneficial in weight management strategies.<br /

Informal caregivers of persons with dementia, their use of and needs for specific professional support: a survey of the national dementia programme

<p>Abstract</p> <p>Background</p> <p>This paper describes both the use of and needs for informal caregivers of people with dementia, based on a questionnaire survey organized within the National Dementia Programme in the Netherlands. The National Dementia Programme is a quality collaborative of the Dutch Alzheimer's Association, the Institute of Quality of Healthcare (CBO) and the Knowledge Centre on Ageing (Vilans), instigated by the Ministry of Health, Welfare and Sport, to improve integrated care for people with dementia and their informal caregivers. The support needs of informal caregivers are important to improve caregiver well-being and delaying institutionalization of the person with dementia.</p> <p>Methods</p> <p>In the period April 2006 - January 2007, the National Dementia Programme questionnaire was completed by 984 informal caregivers. Descriptive statistics were used to analyze the use of and needs for additional professional support by informal caregivers. Chi-square tests were used to assess the relationships between characteristics of the caregivers (spouses, sons/daughters, sons/daughters in-law) and support needs on one hand and to assess the relationship between the living situation of the person with dementia (living at home or living in a nursing home or home for the elderly) and support needs on the other hand.</p> <p>Results</p> <p>Almost all informal caregivers (92.6%) received some professional support. However, two thirds (67.4%) indicated they had one or more needs for additional professional support. Informal caregivers often need additional professional advice about what to do when their relative is frightened, angry of confused. Spouses reported different needs than sons or daughters (in-law): spouses relatively often need emotional support and sons or daughters (in-law) more often need information and coordination of dementia care.</p> <p>Conclusions</p> <p>Most of the informal caregivers report that they need additional information and advice, e.g. about how to cope with behavioral problems of their relative, about the progression of the illness trajectory, emotional support and coordination of dementia care. Future support programmes, e.g. in the field of case management, should address the specific needs of informal caregivers.</p

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment ap-proaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothy-roidism, hyperthyroidism, or thyroid cancer, are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a se-ries of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes

Effect of weight loss, with or without exercise, on body composition and sex hormones in postmenopausal women: the SHAPE-2 trial

Introduction Physical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise. Methods Overweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5–6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry. Results Both the diet (−4.9 kg) and mainly exercise (−5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference −1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared. Conclusions Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormone

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

SIVagm Infection in Wild African Green Monkeys from South Africa: Epidemiology, Natural History, and Evolutionary Considerations

Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity. We performed a large scale study of molecular epidemiology and natural history of SIVagm infection in 225 free-ranging AGMs from multiple locations in South Africa. SIV prevalence (established by sequencing pol, env, and gag) varied dramatically between infant/juvenile (7%) and adult animals (68%) (p<0.0001), and between adult females (78%) and males (57%). Phylogenetic analyses revealed an extensive genetic diversity, including frequent recombination events. Some AGMs harbored epidemiologically linked viruses. Viruses infecting AGMs in the Free State, which are separated from those on the coastal side by the Drakensberg Mountains, formed a separate cluster in the phylogenetic trees; this observation supports a long standing presence of SIV in AGMs, at least from the time of their speciation to their Plio-Pleistocene migration. Specific primers/probes were synthesized based on the pol sequence data and viral loads (VLs) were quantified. VLs were of 104-106 RNA copies/ml, in the range of those observed in experimentally-infected monkeys, validating the experimental approaches in natural hosts. VLs were significantly higher (107-108 RNA copies/ml) in 10 AGMs diagnosed as acutely infected based on SIV seronegativity (Fiebig II), which suggests a very active transmission of SIVagm in the wild. Neither cytokine levels (as biomarkers of immune activation) nor sCD14 levels (a biomarker of microbial translocation) were different between SIV-infected and SIV-uninfected monkeys. This complex algorithm combining sequencing and phylogeny, VL quantification, serology, and testing of surrogate markers of microbial translocation and immune activation permits a systematic investigation of the epidemiology, viral diversity and natural history of SIV infection in wild African natural hosts. © 2013 Ma et al

Does treating obesity stabilize chronic kidney disease?

BACKGROUND: Obesity is a growing health issue in the Western world. Obesity, as part of the metabolic syndrome adds to the morbidity and mortality. The incidence of diabetes and hypertension, two primary etiological factors for chronic renal failure, is significantly higher with obesity. We report a case with morbid obesity whose renal function was stabilized with aggressive management of his obesity. CASE REPORT: A 43-year old morbidly obese Caucasian male was referred for evaluation of his chronic renal failure. He had been hypertensive with well controlled blood pressure with a body mass index of 46 and a baseline serum creatinine of 4.3 mg/dl (estimated glomerular filtration rate of 16 ml/min). He had failed all conservative attempts at weight reduction and hence was referred for a gastric by-pass surgery. Following the bariatric surgery he had approximately 90 lbs. weight loss over 8-months and his serum creatinine stabilized to 4.0 mg/dl. CONCLUSION: Obesity appears to be an independent risk factor for renal failure. Targeting obesity is beneficial not only for better control of hypertension and diabetes, but also possibly helps stabilization of chronic kidney failure

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Quantitative proteomic analysis of the influence of lignin on biofuel production by Clostridium acetobutylicum ATCC 824

Background: Clostridium acetobutylicum has been a focus of research because of its ability to produce high-value compounds that can be used as biofuels. Lignocellulose is a promising feedstock, but the lignin–cellulose–hemicellulose biomass complex requires chemical pre-treatment to yield fermentable saccharides, including cellulose-derived cellobiose, prior to bioproduction of acetone–butanol–ethanol (ABE) and hydrogen. Fermentation capability is limited by lignin and thus process optimization requires knowledge of lignin inhibition. The effects of lignin on cellular metabolism were evaluated for C. acetobutylicum grown on medium containing either cellobiose only or cellobiose plus lignin. Microscopy, gas chromatography and 8-plex iTRAQ-based quantitative proteomic technologies were applied to interrogate the effect of lignin on cellular morphology, fermentation and the proteome. Results: Our results demonstrate that C. acetobutylicum has reduced performance for solvent production when lignin is present in the medium. Medium supplemented with 1 g L−1 of lignin led to delay and decreased solvents production (ethanol; 0.47 g L−1 for cellobiose and 0.27 g L−1 for cellobiose plus lignin and butanol; 0.13 g L−1 for cellobiose and 0.04 g L−1 for cellobiose plus lignin) at 20 and 48 h, respectively, resulting in the accumulation of acetic acid and butyric acid. Of 583 identified proteins (FDR < 1 %), 328 proteins were quantified with at least two unique peptides. Up- or down-regulation of protein expression was determined by comparison of exponential and stationary phases of cellobiose in the presence and absence of lignin. Of relevance, glycolysis and fermentative pathways were mostly down-regulated, during exponential and stationary growth phases in presence of lignin. Moreover, proteins involved in DNA repair, transcription/translation and GTP/ATP-dependent activities were also significantly affected and these changes were associated with altered cell morphology. Conclusions: This is the first comprehensive analysis of the cellular responses of C. acetobutylicum to lignin at metabolic and physiological levels. These data will enable targeted metabolic engineering strategies to optimize biofuel production from biomass by overcoming limitations imposed by the presence of lignin