Identifying the best body-weight-status index associated with metabolic risk in youth

This study investigated the association of six different anthropometric markers with metabolic syndrome to find the most suited to predict children at risk. Sample comprises 1324 Portuguese youth (701 girls, 623 boys), aged 10‐17 years. Six anthropometric markers were included: body mass index (BMI), BMI z‐score, tri‐ponderal index (TPI), waist circumference (WC), WC/height ratio (WC/H), and WC/H adjusted ratio (WC/Hadj). A standardized metabolic risk score (zMR) was computed by summing of standardized values for fasting glucose, triglycerides, high‐density lipoprotein cholesterol, and mean arterial blood pressure. The associations between zMR and anthropometric markers were assessed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal values that best predict metabolic risk of each anthropometric marker. Among the studied predictors, BMI z‐score, followed by BMI and WC, was most highly associated with zMR, while WC/Hadj was the weakest predictor. ROC analyses showed significant AUCs for all markers, yet the discrimination was poor (AUCs from 0.60 to 0.68), with sensitivity ranging from 45.5% to 67.5% and specificity from 72.6% to 81.9%. The optimal cut‐off values to predict metabolic risk were 1.62, 23.1 kg/m2, 71.0 cm, 18.0 kg/m3, 0.47, and 0.50, for BMI z‐score, BMI, WC, TPI, WC/H, and WC/Hadj, respectively. BMI z‐score, followed by BMI and WC, were the most relevant anthropometric markers to predict metabolic risk in youth, while WC/Hadj was the worst predictor. Results suggest that anthropometric markers should continue to be used as clinical tools to identify youth at risk

An ontology-based segmentation scheme for tracking postnatal changes in the developing rodent brain with MRI

The postnatal period of neurodevelopment has been implicated in a number of brain disorders including autism and schizophrenia. Rodent models have proven to be invaluable in advancing our understanding of the human brain, and will almost certainly play a pivotal role in future studies on postnatal neurodevelopment. The growing field of magnetic resonance microscopy has the potential to revolutionize our understanding of neurodevelopment, if it can be successfully and appropriately assimilated into the vast body of existing neuroscience research. In this study, we demonstrate the utility of a developmental neuro-ontology designed specifically for tracking regional changes in MR biomarkers throughout postnatal neurodevelopment. Using this ontological classification as a segmentation guide, we track regional changes in brain volume in rats between postnatal day zero and postnatal day 80 and demonstrate differential growth rates in axial versus paraxial brain regions. Both the ontology and the associated label volumes are provided as a foundation for future MR-based studies of postnatal neurodevelopment in normal and disease states

Development of a healthy biscuit: an alternative approach to biscuit manufacture

OBJECTIVE: Obesity (BMI >30) and related health problems, including coronary heart disease (CHD), is without question a public health concern. The purpose of this study was to modify a traditional biscuit by the addition of vitamin B(6), vitamin B(12), Folic Acid, Vitamin C and Prebiotic fibre, while reducing salt and sugar. DESIGN: Development and commercial manufacture of the functional biscuit was carried out in collaboration with a well known and respected biscuit manufacturer of International reputation. The raw materials traditionally referred to as essential in biscuit manufacture, i.e. sugar and fat, were targeted for removal or reduction. In addition, salt was completely removed from the recipe. PARTICIPANTS: University students of both sexes (n = 25) agreed to act as subjects for the study. Ethical approval for the study was granted by the University ethics committee. The test was conducted as a single blind crossover design, and the modified and traditional biscuits were presented to the subjects under the same experimental conditions in a random fashion. RESULTS: No difference was observed between the original and the modified product for taste and consistency (P > 0.05). The modified biscuit was acceptable to the consumer in terms of eating quality, flavour and colour. Commercial acceptability was therefore established. CONCLUSION: This study has confirmed that traditional high-fat and high-sugar biscuits which are not associated with healthy diets by most consumers can be modified to produce a healthy alternative that can be manufactured under strict commercial conditions

Induction of IFN-β and the Innate Antiviral Response in Myeloid Cells Occurs through an IPS-1-Dependent Signal That Does Not Require IRF-3 and IRF-7

Interferon regulatory factors (IRF)-3 and IRF-7 are master transcriptional factors that regulate type I IFN gene (IFN-α/β) induction and innate immune defenses after virus infection. Prior studies in mice with single deletions of the IRF-3 or IRF-7 genes showed increased vulnerability to West Nile virus (WNV) infection. Whereas mice and cells lacking IRF-7 showed reduced IFN-α levels after WNV infection, those lacking IRF-3 or IRF-7 had relatively normal IFN-b production. Here, we generated IRF-3−/−× IRF-7−/− double knockout (DKO) mice, analyzed WNV pathogenesis, IFN responses, and signaling of innate defenses. Compared to wild type mice, the DKO mice exhibited a blunted but not abrogated systemic IFN response and sustained uncontrolled WNV replication leading to rapid mortality. Ex vivo analysis showed complete ablation of the IFN-α response in DKO fibroblasts, macrophages, dendritic cells, and cortical neurons and a substantial decrease of the IFN-β response in DKO fibroblasts and cortical neurons. In contrast, the IFN-β response was minimally diminished in DKO macrophages and dendritic cells. However, pharmacological inhibition of NF-κB and ATF-2/c-Jun, the two other known components of the IFN-β enhanceosome, strongly reduced IFN-β gene transcription in the DKO dendritic cells. Finally, a genetic deficiency of IPS-1, an adaptor involved in RIG-I- and MDA5-mediated antiviral signaling, completely abolished the IFN-β response after WNV infection. Overall, our experiments suggest that, unlike fibroblasts and cortical neurons, IFN-β gene regulation after WNV infection in myeloid cells is IPS-1-dependent but does not require full occupancy of the IFN-β enhanceosome by canonical constituent transcriptional factors

Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells

Background: Histone deacetylase inhibitors (HDACis) are promising anticancer drugs; however, the molecular mechanisms leading to HDACi-induced cell death have not been well understood and no clear mechanism of resistance has been elucidated to explain limited efficacy of HDACis in clinical trials. Methods and Findings: Here, we show that protein levels of checkpoint kinase 1 (Chk1), which has a major role in G2 cell cycle checkpoint regulation, was markedly reduced at the protein and transcriptional levels in lung cancer cells treated with pan-and selective HDACis LBH589, scriptaid, valproic acid, apicidin, and MS-275. In HDACi treated cells Chk1 function was impaired as determined by decreased inhibitory phosphorylation of cdc25c and its downstream target cdc2 and increased expression of cdc25A and phosphorylated histone H3, a marker of mitotic entry. In time course experiments, Chk1 downregulation occurred after HDACi treatment, preceding apoptosis. Ectopic expression of Chk1 overcame HDACiinduced cell death, and pretreating cells with the cdc2 inhibitor purvalanol A blocked entry into mitosis and prevented cell death by HDACis. Finally, pharmacological inhibition of Chk1 showed strong synergistic effect with LBH589 in lung cancer cells. Conclusions: These results define a pathway through which Chk1 inhibition can mediate HDACi-induced mitotic entry and cell death and suggest that Chk1 could be an early pharmacodynamic marker to assess HDACi efficacy in clinical samples

Carbohydrate, phenolic and antioxidant level in relation to chlorophyll a content in oilseed winter rape (Brassica napus L.) inoculated with Leptosphaeria maculans

Syftet med föreliggande studien var att undersöka om sjuksköterskors egna rökvanor påverkar attityden till tobakspreventivt arbete på sjukhuset, både till tobakspreventivt arbete med patienterna och attityden till rökfritt sjukhus. Studien är empirisk och utfördes genom kvalitativa intervjuer med sex sjuksköterskor på en vårdavdelning på ett sjukhus i södra Sverige. Data från intervjuerna analyserades och resulterade i sju olika teman: Preventiva rollen, Kunskap om prevention, Vem skall leda det preventiva arbetet, Rökkontroll, Utbildningsnivå och rökning, Sjuksköterskan, en förebild?, Vem ska hjälpa patienten vid rökstopp på sjukhuset?, Är det någon skillnad mellan icke rökande och rökande vad avser rökpreventionen?. Den preventiva rollen hamnade i fokus och skillnader fanns mellan rökande och icke rökande sjuksköterskor både vad gäller preventivt omvårdnasarbete och kontrollThe aim of the present study is to investigate whether nurses smoking habits influence their attitude to tobacco prevention in hospitals, both in their work with patients and regarding their attitude to hospital smoking bans. The following question was posed: is there a difference between smoking and non-smoking nurses in patient-care activities regarding smoking prevention and control? The study is qualitative, based on qualitative interviews with six nurses at a ward of a hospital in Sweden. Interview data were analyzed and eight themes emerged: the role in prevention work knowledge of prevention who is to lead prevention work smoking control smoking and education levels the nurse as a role model who is to help the patient give up smoking possible differences between nonsmoking and smoking nurses regarding smoking prevention. The role in prevention work turned out to be central. Smoking nurses had greater difficulties in connection with preventive work and control, due to their personal experience of how hard it can be to give up smoking habits

Comparative 3D QSAR study on β1-, β2-, and β3-adrenoceptor agonists

A quantitative structure–activity relationship study of tryptamine-based derivatives of β1-, β2-, and β3-adrenoceptor agonists was conducted using comparative molecular field analysis (CoMFA). Correlation coefficients (cross-validated r2) of 0.578, 0.595, and 0.558 were obtained for the three subtypes, respectively, in three different CoMFA models. All three CoMFA models have different steric and electrostatic contributions, implying different requirements inside the binding cavity. The CoMFA coefficient contour plots of the three models and comparisons among these plots provide clues regarding the main chemical features responsible for the biological activity variations and also result in predictions which correlate very well with the observed biological activity. Based on the analysis, a summary regeospecific description of the requirements for improving β-adrenoceptor subtype selectivity is given

Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult

Research reported in this publication was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R01AR60361, R01AR061988, P41EB002520). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ART was supported by a National Science Foundation Graduate Fellowship

A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken

Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3), a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals