The genetic basis of DOORS syndrome: an exome-sequencing study.

Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the genetic basis of this syndrome by sequencing most coding exons in affected individuals

Experiences and attitudes of Dutch rheumatologists and oncologists with regard to their patients’ health-related Internet use

The objective of this study is to explore the experiences and attitudes of rheumatologists and oncologists with regard to their patients’ health-related Internet use. In addition, we explored how often physicians referred their patients to health-related Internet sites. We sent a questionnaire to all the rheumatologists and oncologists in the Netherlands. The questionnaire included questions concerning demographics, experiences with patients’ health-related Internet use, referral behavior, and attitudes to the consequences of patients’ health-related Internet use (for patients themselves, the physician-patient relationship and the health care). The response rate was 46% (N = 238). Of these respondents, 134 practiced as a rheumatologist and 104 as an oncologist. Almost all physicians encountered their patients raising information from the Internet during a consultation. They were not, however, confronted with their patients’ health-related Internet use on a daily basis. Physicians had a moderately positive attitude towards the consequences of patients’ health-related Internet use, the physician-patient relationship and the health care. Oncologists were significantly less positive than rheumatologists about the consequences of health-related Internet use. Most of the physicians had never (32%) or only sometimes (42%) referred a patient to a health-related Internet site. Most physicians (53%) found it difficult to stay up-to-date with reliable Internet sites for patients. Physicians are moderately positive about their patients’ health-related Internet use but only seldom refer them to relevant sites. Offering an up-to-date site with accredited websites for patients might help physicians refer their patients

Statistical Power to Detect Genetic Loci Affecting Environmental Sensitivity

There is evidence in different species of genetic control of environmental variation, independent of scale effects. The statistical power to detect genetic control of environmental or phenotypic variability for a quantitative trait was investigated analytically using a monozygotic (MZ) twin difference design and a design using unrelated individuals. The model assumed multiplicative or additive effects of alleles on trait variance at a bi-allelic locus and an additive (regression) model for statistical analysis. If genetic control acts on phenotypic variance then the design using unrelated individuals is more efficient but 10,000s of observations are needed to detect loci explaining at most 3.5% of the variance of the variance at genome-wide significance. If genetic control acts purely on environmental variation then an MZ twin difference design is more efficient when the MZ trait correlation is larger than ~0.3. For a locus that explains a given proportion of the variation in variance, twice the number of observations is needed for detection when compared to a locus that explains the same proportion of variation in phenotypes. © 2010 Springer Science+Business Media, LLC

The effects of lifestyle interventions on (long-term) weight management, cardiometabolic risk and depressive symptoms in people with psychotic disorders:A meta-analysis

AIMS: The aim of this study was to estimate the effects of lifestyle interventions on bodyweight and other cardiometabolic risk factors in people with psychotic disorders. Additionally, the long-term effects on body weight and the effects on depressive symptoms were examined. MATERIAL AND METHODS: We searched four databases for randomized controlled trials (RCTs) that compared lifestyle interventions to control conditions in patients with psychotic disorders. Lifestyle interventions were aimed at weight loss or weight gain prevention, and the study outcomes included bodyweight or metabolic parameters. RESULTS: The search resulted in 25 RCTs -only 4 were considered high quality- showing an overall effect of lifestyle interventions on bodyweight (effect size (ES)  =  -0.63, p<0.0001). Lifestyle interventions were effective in both weight loss (ES =  -0.52, p<0.0001) and weight-gain-prevention (ES =  -0.84, p = 0.0002). There were significant long-term effects, two to six months post-intervention, for both weight-gain-prevention interventions (ES =  -0.85, p = 0.0002) and weight loss studies (ES =  -0.46, p = 0.02). Up to ten studies reported on cardiometabolic risk factors and showed that lifestyle interventions led to significant improvements in waist circumference, triglycerides, fasting glucose and insulin. No significant effects were found for blood pressure and cholesterol levels. Four studies reported on depressive symptoms and showed a significant effect (ES =  -0.95, p = 0.05). CONCLUSION: Lifestyle interventions are effective in treating and preventing obesity, and in reducing cardiometabolic risk factors. However, the quality of the studies leaves much to be desired

Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages

Shann S Yu1,2, Cheryl M Lau1, Susan N Thomas3, W Gray Jerome4, David J Maron5, James H Dickerson2,6, Jeffrey A Hubbell3, Todd D Giorgio1,2,7,81Department of Biomedical Engineering, Vanderbilt University, Nashville, 2Vanderbilt Institute of Nanoscale Science and Engineering, Nashville, TN, USA; 3Institute of Bioengineering, &amp;Eacute;cole Polytechnique F&amp;eacute;d&amp;eacute;rale de Lausanne, Lausanne, Switzerland, 4Department of Pathology, Vanderbilt University Medical Center, Nashville, 5Vanderbilt Heart and Vascular Institute, Nashville, 6Department of Physics and Astronomy, Vanderbilt University, Nashville, 7Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, 8Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USAAbstract: The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30&amp;ndash;100 nm in diameter and -23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10&amp;ndash;20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T2-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states.Keywords: macrophage targeting, poly(ethylene glycol) (PEG), poly(propylene sulfide) (PPS), iron oxides, opsonizatio