Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG

Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

Background: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti- inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 mM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl 2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 mg/kg) significantly lengthened the QT c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT c . Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 mM) decreased the amplitude of rapid (I Kr ) and slow (I Ks ) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I Ca ) was slightly diminished, but the transient outward (I to ) and inward rectifier (I K1 ) potassium currents were not influenced. Conclusions: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve

Genetics of CM-proteins (A-hordeins) in barley

The CM-proteins, which are the main components of the A-hordeins, include four previously described proteins (CMa-1, CMb-1, CMc-1, CMd-1), plus a new one, CMe-1, which has been tentatively included in this group on the basis of its solubility properties and electrophoretic mobility. The variability of the five proteins has been investigated among 38 Hordeum vulgare cultivars and 17 H. spontaneum accessions. Proteins CMa-1, CMc-1 and CMd-1 were invariant within the cultivated species; CMd was also invariant in the wild one. The inheritance of variants CMb-1/CMb-2 and CMe-1/CMe-2,2 was studied in a cross H. spontaneum x H. vulgare. The first two proteins were inherited as codominantly expressed allelic variations of a single mendelian gene. Components CMe-2,2 were jointly inherited and codominantly expressed with respect to CMe-1. Gene CMb and gene(s) CMe were found to be unlinked. The chromosomal locations of genes encoding CM-proteins were investigated using wheat-barley addition lines. Genes CMa and CMc were associated with chromosome 1, and genes CMb and CMd with chromosome 4. These gene locations further support the proposed homoeology of chromosomes 1 and 4 of barley with chromosomes groups 7 and 4 of wheat, respectively. Gene(s) CMe has been assigned to chromosome 3 of barley. The accumulation of protein CMe-1 is totally blocked in the high lysine mutant Riso 1508 and partially so in the high lysine barley Hiproly

Glaciotectonic deformation associated with the Orient Point–Fishers Island moraine, westernmost Block Island Sound : further evidence of readvance of the Laurentide ice sheet

This paper is not subject to U.S. copyright. The definitive version was published in Geo-Marine Letters 32 (2012): 279-288, doi:10.1007/s00367-012-0296-9.High-resolution seismic-reflection profiles collected across pro-glacial outwash deposits adjacent to the circa 18 ka b.p. Orient Point–Fishers Island end moraine segment in westernmost Block Island Sound reveal extensive deformation. A rhythmic seismic facies indicates the host outwash deposits are composed of fine-grained glaciolacustrine sediments. The deformation is variably brittle and ductile, but predominantly compressive in nature. Brittle deformation includes reverse faults and thrust faults that strike parallel to the moraine, and thrust sheets that extend from beneath the moraine. Ductile deformation includes folded sediments that overlie undisturbed deposits, showing that they are not drape features. Other seismic evidence for compression along the ice front consists of undisturbed glaciolacustrine strata that dip back toward and underneath the moraine, and angular unconformities on the sea floor where deformed sediments extend above the surrounding undisturbed correlative strata. Together, these ice-marginal glaciotectonic features indicate that the Orient Point–Fishers Island moraine marks a significant readvance of the Laurentide ice sheet, consistent with existing knowledge for neighboring coeval moraines, and not simply a stillstand as previously reported.This work was supported by the Connecticut Department of Environmental Protection, and the Atlantic Hydrographic Branch of the National Oceanic and Atmospheric Administration.2013-06-2

The use of therapy dogs to support court users in the waiting room

The use of animals to support individuals' wellbeing has been documented across a variety of disciplines. It has been over a decade since dogs have also started to be used within the criminal justice setting in America to support vulnerable people, but this practice is not common in the United Kingdom. Globally, empirical evidence to support the benefits of utilising dogs within the criminal justice system is lacking. The present interdisciplinary study aimed to explore one aspect of the criminal justice journey, the impact a therapy dog can have on UK court users waiting to give evidence at a magistrate's court. 117 court users and 8 court staff were interviewed to explore their perceptions of a therapy dog service offered at a local magistrates’ court. Using thematic analysis, three main themes were discovered: (1) Context of the court environment, (2) Effect of the therapy dog on well-being, and (3) Issues relating to therapy dogs in court waiting areas. Results suggests that therapy dogs have a number of benefits to court users. Long-term, the human-canine interaction positively translates into the court waiting room environment and so it should be further explored, evaluated and then appropriately implemented in the UK’s legal system

Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty

BACKGROUND: The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. RESULTS: Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45-55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. CONCLUSION: Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs

Childhood emotional problems and self-perceptions predict weight gain in a longitudinal regression model

<p>Abstract</p> <p>Background</p> <p>Obesity and weight gain are correlated with psychological ill health. We predicted that childhood emotional problems and self-perceptions predict weight gain into adulthood.</p> <p>Methods</p> <p>Data on around 6,500 individuals was taken from the 1970 Birth Cohort Study. This sample was a representative sample of individuals born in the UK in one week in 1970. Body mass index was measured by a trained nurse at the age of 10 years, and self-reported at age 30 years. Childhood emotional problems were indexed using the Rutter B scale and self-report. Self-esteem was measured using the LAWSEQ questionnaire, whilst the CARALOC scale was used to measure locus of control.</p> <p>Results</p> <p>Controlling for childhood body mass index, parental body mass index, and social class, childhood emotional problems as measured by the Rutter scale predicted weight gain in women only (least squares regression <it>N </it>= 3,359; coefficient 0.004; <it>P </it>= 0.032). Using the same methods, childhood self-esteem predicted weight gain in both men and women (<it>N </it>= 6,526; coefficient 0.023; <it>P </it>< 0.001), although the effect was stronger in women. An external locus of control predicted weight gain in both men and women (<it>N </it>= 6,522; coefficient 0.022; <it>P </it>< 0.001).</p> <p>Conclusion</p> <p>Emotional problems, low self-esteem and an external locus of control in childhood predict weight gain into adulthood. This has important clinical implications as it highlights a direction for early intervention strategies that may contribute to efforts to combat the current obesity epidemic.</p

What Do We Know About Contracting Out in the United States? Evidence from Household and Establishment Surveys

A variety of evidence points to significant growth in domestic contracting out over the last two decades, yet the phenomenon is not well documented. In this paper, we pull together data from various sources to shed light on the extent of and trends in domestic outsourcing, the occupations in which it has grown, and the industries engaging in outsourcing for the employment services sector, which has been a particularly important area of domestic outsourcing. In addition, we examine evidence of contracting out of selected occupations to other sectors. We point to many gaps in our knowledge on trends in domestic outsourcing and its implications for employment patterns and to inconsistencies across data sets in the information that is available. We recommend steps to improve data in this area

Association of Estimated Glomerular Filtration Rate and Urinary Uromodulin Concentrations with Rare Variants Identified by UMOD Gene Region Sequencing

Background: Recent genome-wide association studies (GWAS) have identified common variants in the UMOD region associated with kidney function and disease in the general population. To identify novel rare variants as well as common variants that may account for this GWAS signal, the exons and 4 kb upstream region of UMOD were sequenced. Methodology/Principal Findings Individuals (n = 485) were selected based on presence of the GWAS risk haplotype and chronic kidney disease (CKD) in the ARIC Study and on the extremes of of the UMOD gene product, uromodulin, in urine (Tamm Horsfall protein, THP) in the Framingham Heart Study (FHS). Targeted sequencing was conducted using capillary based Sanger sequencing (3730 DNA Analyzer). Variants were tested for association with THP concentrations and estimated glomerular filtration rate (eGFR), and identified non-synonymous coding variants were genotyped in up to 22,546 follow-up samples. Twenty-four and 63 variants were identified in the 285 ARIC and 200 FHS participants, respectively. In both studies combined, there were 33 common and 54 rare (MAF<0.05) variants. Five non-synonymous rare variants were identified in FHS; borderline enrichment of rare variants was found in the extremes of THP (SKAT p-value = 0.08). Only V458L was associated with THP in the FHS general-population validation sample (p = 9*10$^{−3}$, n = 2,522), but did not show direction-consistent and significant association with eGFR in both the ARIC (n = 14,635) and FHS (n = 7,520) validation samples. Pooling all non-synonymous rare variants except V458L together showed non-significant associations with THP and eGFR in the FHS validation sample. Functional studies of V458L revealed no alternations in protein trafficking. Conclusions/Significance: Multiple novel rare variants in the UMOD region were identified, but none were consistently associated with eGFR in two independent study samples. Only V458L had modest association with THP levels in the general population and thus could not account for the observed GWAS signal