Activity of different desoximetasone preparations compared to other topical corticosteroids in the vasoconstriction assay

Introduction: We report on a double-blind, vehicle-controlled, single-center confirmatory study with random assignment. The purpose of the study was to investigate the topical bioavailability of different topical corticosteroid formulations in healthy human beings focussing on desoximetasone (DM). Materials and Methods: Two DM 0.25% formulations {[}ointment (DM-o) and fatty ointment (DM-fo, water-free); class III corticosteroids], the corresponding active ingredient-free vehicles and three comparators of different strength {[}clobetasol propionate 0.05% (CP 0.05%), fatty ointment, class IV; hydrocortisone (HC) 1%, fatty ointment, class I, and betamethasone (BM) 0.05%, fatty ointment, class III] were tested using the vasoconstriction assay. The degree of vasoconstriction (blanching) in the treatment field was compared to the one found in untreated control fields using chromametric measurements and clinical assessment. Results/Conclusion: DM-o 0.25%, DM-fo 0.25% and BM 0.05% showed similar vasoconstrictive potential, i.e., clear blanching. In fact, both DM preparations were proven to be non-inferior to BM 0.05%, while CP 0.05% was found a little less active. HC 1.0% and the DM vehicles showed no clear-cut vasoconstrictive effect. No adverse events related to the study medications were observed. Good topical bioavailability of both DM formulations was detected by chromametric measurement and clinical assessment. Copyright (C) 2008 S. Karger AG, Basel

Lumbar spine and total-body dual-energy X-ray absorptiometry in children with severe neurological impairment and intellectual disability: a pilot study of artefacts and disrupting factors

Background Children with severe neurological impairment and intellectual disability (ID) are susceptible for developing low bone mineral density (BMD) and fractures. BMD is generally measured with dual-energy X-ray absorptiometry (DXA). Objective To describe the occurrence of factors that may influence the feasibility of DXA and the accuracy of DXA outcome in children with severe neurological impairment and ID. Materials and methods Based on literature and expert opinion, a list of disrupting factors was developed. Occurrence of these factors was assessed in 27 children who underwent DXA measurement. Results Disrupting factors that occurred most frequently were movement during measurement (82%), aberrant body composition (67%), small length for age (56%) and scoliosis (37%). The number of disrupting factors per child was mean 5.3 (range 1-8). No correlation was found between DXA outcomes and the number of disrupting factors. Conclusion Factors that may negatively influence the accuracy of DXA outcome are frequently present in children with severe neurological impairment and ID. No systematic deviation of DXA outcome in coherence with the amount of disrupting factors was found, but physicians should be aware of the possible influence of disrupting factors on the accuracy of DXA

Interpreting 16S metagenomic data without clustering to achieve sub-OTU resolution

The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.Comment: Updated to match the published version. 12 pages, 5 figures + supplement. Significantly revised for clarity, references added, results not change

Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol

Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder characterized by progressive neuronal dysfunction and premature death. Recently, the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes cysteine string protein alpha. We show here that mutating dnj-14, the Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a small impairment of locomotion and neurotransmission. Mutant dnj-14 worms also exhibited age-dependent neurodegeneration of sensory neurons, which was preceded by severe progressive chemosensory defects. A focussed chemical screen revealed that resveratrol could ameliorate dnj-14 mutant phenotypes, an effect mimicked by the cAMP phosphodiesterase inhibitor, rolipram. In contrast to other worm neurodegeneration models, activation of the Sirtuin, SIR-2.1, was not required, as sir-2.1; dnj-14 double mutants showed full lifespan rescue by resveratrol. The Sirtuin-independent neuroprotective action of resveratrol revealed here suggests potential therapeutic applications for ANCL and possibly other human neurodegenerative diseases

Quasinormal modes of massive charged flavor branes

We present an analysis and classification of vector and scalar fluctuations in a D3/D7 brane setup at finite termperature and baryon density. The system is dual to an N=2 supersymmetric Yang-Mills theory with SU(N_c) gauge group and N_f hypermultiplets in the fundamental representation in the quenched approximation. We improve significantly over previous results on the quasinormal mode spectrum of D7 branes and stress their novel physical interpretation. Amongst our findings is a new purely imaginary scalar mode that becomes tachyonic at sufficiently low temperature and baryon density. We establish the existence of a critical density above which the scalar mode stays in the stable regime for all temperatures. In the vector sector we study the crossover from the hydrodynamic to the quasiparticle regime and find that it moves to shorter wavelengths for lower temperatures. At zero baryon density the quasinormal modes move toward distinct discrete attractor frequencies that depend on the momentum as we increase the temperature. At finite baryon density, however, the trajectories show a turning behavior such that for low temperature the quasinormal mode spectrum approaches the spectrum of the supersymmetric zero temperature normal modes. We interpret this as resolution of the singular quasinormal mode spectrum that appears at the limiting D7 brane embedding at vanishing baryon density.Comment: 56 pages, 40 figure

A novel locus for Meckel-Gruber syndrome, MKS3, maps to chromosome 8q24

Meckel-Gruber syndrome (MKS), the most common monogenic cause of neural tube defects, is an autosomal recessive disorder characterised by a combination of renal cysts and variably associated features, including developmental anomalies of the central nervous system (typically encephalcoele), hepatic ductal dysplasia and cysts, and polydactyly. Locus heterogeneity has been demonstrated by the mapping of the MKS1 locus to 17q21-24 in Finnish kindreds, and of MKS2 to 11q13 in North African-Middle Eastern cohorts. In the present study, we have investigated the genetic basis of MKS in eight consanguineous kindreds, originating from the Indian sub-continent, that do not show linkage to either MKS1 or MKS2. We report the localisation of a third MKS locus (MKS3) to chromosome 8q24 in this cohort by a genome-wide linkage search using autozygosity mapping. We identified a 26-cM region of autozygosity between D8S586 and D8S1108 with a maximum cumulative two-point LOD score at D8S1179 (Z(max)=3.04 at theta=0.06). A heterogeneity test provided evidence of one unlinked family. Exclusion of this family from multipoint analysis maximised the cumulative multipoint LOD score at locus D8S1128 (Z(max)=5.65). Furthermore, a heterozygous SNP in DDEF1, a putative candidate gene, suggested that MKS3 mapped within a 15-cM interval. Comparison of the clinical features of MKS3-linked cases with reports of MKS1- and MKS2-linked kindreds suggests that polydactyly (and possibly encephalocele) appear less common in MKS3-linked families

IMI Risk Factors for Myopia

Risk factor analysis provides an important basis for developing interventions for any condition. In the case of myopia, evidence for a large number of risk factors has been presented, but they have not been systematically tested for confounding. To be useful for designing preventive interventions, risk factor analysis ideally needs to be carried through to demonstration of a causal connection, with a defined mechanism. Statistical analysis is often complicated by covariation of variables, and demonstration of a causal relationship between a factor and myopia using Mendelian randomization or in a randomized clinical trial should be aimed for. When strict analysis of this kind is applied, associations between various measures of educational pressure and myopia are consistently observed. However, associations between more nearwork and more myopia are generally weak and inconsistent, but have been supported by meta-analysis. Associations between time outdoors and less myopia are stronger and more consistently observed, including by meta-analysis. Measurement of nearwork and time outdoors has traditionally been performed with questionnaires, but is increasingly being pursued with wearable objective devices. A causal link between increased years of education and more myopia has been confirmed by Mendelian randomization, whereas the protective effect of increased time outdoors from the development of myopia has been confirmed in randomized clinical trials. Other proposed risk factors need to be tested to see if they modulate these variables. The evidence linking increased screen time to myopia is weak and inconsistent, although limitations on screen time are increasingly under consideration as interventions to control the epidemic of myopia

A school-based intervention incorporating smartphone technology to improve health-related fitness among adolescents: Rationale and study protocol for the NEAT and ATLAS 2.0 cluster randomised controlled trial and dissemination study

Introduction Physical inactivity has been described as a global pandemic. Interventions aimed at developing skills in lifelong physical activities may provide the foundation for an active lifestyle into adulthood. In general, school-based physical activity interventions targeting adolescents have produced modest results and few have been designed to be \u27scaled-up\u27 and disseminated. This study aims to: (1) assess the effectiveness of two physical activity promotion programmes (ie, NEAT and ATLAS) that have been modified for scalability; and (2) evaluate the dissemination of these programmes throughout government funded secondary schools. Methods and analysis The study will be conducted in two phases. In the first phase (cluster randomised controlled trial), 16 schools will be randomly allocated to the intervention or a usual care control condition. In the second phase, the Reach, Effectiveness, Adoption, Implementation and Maintenance (Re-AIM) framework will be used to guide the design and evaluation of programme dissemination throughout New South Wales (NSW), Australia. In both phases, teachers will be trained to deliver the NEAT and ATLAS programmes, which will include: (1) interactive student seminars; (2) structured physical activity programmes; (3) lunch-time fitness sessions; and (4) web-based smartphone apps. In the cluster RCT, study outcomes will be assessed at baseline, 6 months (primary end point) and 12-months. Muscular fitness will be the primary outcome and secondary outcomes will include: objectively measured body composition, cardiorespiratory fitness, flexibility, resistance training skill competency, physical activity, self-reported recreational screen-time, sleep, sugar-sweetened beverage and junk food snack consumption, self-esteem and well-being

Public consciousness and willingness to embrace ethical consumption of textile products in Mexico

The Mexican economy has been showing a continuous and arguably remarkable growth in the last decade, and it is expected that this strong economic growth is based on a balance between social equity, fiscal growth and environmental protection. This composite situation requires us to have a clear understanding of changes in consumer behaviour and their attitudes towards ethical consumerism in this region. With the use of a semi-structured questionnaire, this pilot study presented a detailed analysis of the consumer attitudes towards ethical consumerism in relation to their socio economic class levels in this region, the public consciousness and willingness to embrace ethical consumption of textile products in Mexico were thus determined. It is hoped that this knowledge provides the basis for the initiation of a framework of activities and measures to develop sustainable consumption habits and to educate consumers on the subject of ethical consumption