Why lose weight? Reasons for seeking weight loss by overweight but otherwise healthy men

OBJECTIVE: To identify the reasons for seeking weight loss in overweight or obese but otherwise healthy men. DESIGN: Interviews, prior to intervention, with subjects who had volunteered to participate in a work-site-based weight loss study. SUBJECTS: Ninety-one overweight=obese male workers. Mean age 41, range 18 – 55 y, mean body mass index (BMI) 31.0, range 26.2 – 41.6 kg=m2. MEASUREMENTS: Anthropometric measurements; body weight and height. Body mass index calculated. A short interview using open questions to determine the individuals reason for seeking weight loss. RESULTS: The message that weight loss is beneficial to health for the overweight was recognized by all subjects regardless of BMI, and was reported as the main factor for attempting weight loss. Improved fitness and effects on appearance and well-being were reported half as often as the primary reason for weight loss. CONCLUSION: Overweight lay members of the public have accepted the health education message that weight loss can improve health. Overweight but otherwise healthy men who responded, of their own accord, to an electronic mail message offering help to lose weight did not regard obesity and overweight as primarily a cosmetic issue. This is still, however, important, especially to younger people

Imaging the neuroendocrinology of appetite.

Functional magnetic resonance imaging has become a powerful tool to investigate the neuroendocrinology of appetite. In a recent study, we demonstrated that the brain activation pattern seen following the infusion of the anorectic gut hormones PYY3-36and GLP-17-36 amideto fasted individuals resembles the brain activation pattern seen in the physiological satiated state. This commentary discusses the significance of these findings and compares them with other landmark studies in the field, with specific reference to the brain areas involved in appetite regulation. We highlight the importance of this type of research in order to pave the way for the development of efficacious and safe anti-obesity therapies

Ocean temperature and salinity components of the Madden-Julian oscillation observed by Argo floats

New diagnostics of the Madden-Julian Oscillation (MJO) cycle in ocean temperature and, for the first time, salinity are presented. The MJO composites are based on 4 years of gridded Argo float data from 2003 to 2006, and extend from the surface to 1,400 m depth in the tropical Indian and Pacific Oceans. The MJO surface salinity anomalies are consistent with precipitation minus evaporation fluxes in the Indian Ocean, and with anomalous zonal advection in the Pacific. The Argo sea surface temperature and thermocline depth anomalies are consistent with previous studies using other data sets. The near-surface density changes due to salinity are comparable to, and partially offset, those due to temperature, emphasising the importance of including salinity as well as temperature changes in mixed-layer modelling of tropical intraseasonal processes. The MJO-forced equatorial Kelvin wave that propagates along the thermocline in the Pacific extends down into the deep ocean, to at least 1,400 m. Coherent, statistically significant, MJO temperature and salinity anomalies are also present in the deep Indian Ocean

Go-stimuli proportion influences response strategy in a sustained attention to response task

The sustained attention to response task (SART) usefulness as a measure of sustained attention has been questioned. The SART may instead be a better measure of other psychological processes and could prove useful in understanding some real-world behaviours. Thirty participants completed four Go/No-Go response tasks much like the SART, with Go-stimuli proportions of .50, .65, .80 and .95. As Go-stimuli proportion increased, reaction times decreased while both commission errors and self-reported task-related thoughts increased. Performance measures were associated with task-related thoughts but not taskunrelated thoughts. Instead of faster reaction times and increased commission errors being due to absentmindedness or perceptual decoupling from the task, the results suggested participants made use of two competing response strategies, in line with a response strategy or response inhibition perspective of SART performance. Interestingly, performance measures changed in a nonlinear manner, despite the linear Go proportion increase. A threshold may exist where the prepotent motor response becomes more pronounced, leading to the disproportionate increase in response speed and commission errors. This research has implications for researchers looking to employ the SAR

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain

This is the final version of the article. Available from Springer Nature via the DOI in this record.Functional neuroimaging, using genetically-encoded Ca(2+) sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.This work was funded by the Biological and Biotechnology Research Council (CASE studentship BB/L502510/1, with AstraZeneca Safety Health and Environment), and by the University of Exeter and AstraZeneca

Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons

Metabotropic glutamate receptors (mGluRs), including mGluR5, play a central role in regulating the strength and plasticity of synaptic connections in the brain. However, the signaling pathways that connect mGluRs to their downstream effectors are not yet fully understood. Here, we report that stimulation of mGluR5 in hippocampal cultures and slices results in phosphorylation of protein kinase D (PKD) at the autophosphorylation site Ser-916. This phosphorylation event occurs within 30 s of stimulation, persists for at least 24 h, and is dependent on activation of phospholipase C and protein kinase C. Our data suggest that activation of PKD may represent a novel signaling pathway linking mGluR5 to its downstream targets. These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity.Howard Hughes Medical InstituteFRAXA Research FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.

Negative emotions in children with newly diagnosed epilepsy.

Purpose: To understand the emotional predicament in children with recently diagnosed idiopathic or cryptogenic epilepsy. Methods: We used the well-tried method of structured projection for the first time in children with epilepsy. Thirty-six children with epilepsy, aged 7-15 years (mean age, 9.5 years) and in 35 control children aged 7-15 years (mean age, 9.4 years), attributed shame and guilt in relation to three types of situation (non- illness related, illness related, and epilepsy related). Children were evaluated twice: shortly after diagnosis, before antiepileptic drug (AED) use and after an interval of 3 months. Results: Children with epilepsy and healthy controls were similar in their way of attributing shame and guilt. However, the type of situation was of influence: Both children with epilepsy and healthy children attributed more shame to incompetence due to epilepsy than to incompetence due to other illnesses. Conclusions: Increased affective problems in childhood epilepsy cannot be explained by excessive attribution of shame and guilt, affects known to be important precursors of psychopathology, yet both healthy children and children with epilepsy attribute more shame to epilepsy than to other illnesses. Epilepsy is not like any other disease

Using combined diagnostic test results to hindcast trends of infection from cross-sectional data

Infectious disease surveillance is key to limiting the consequences from infectious pathogens and maintaining animal and public health. Following the detection of a disease outbreak, a response in proportion to the severity of the outbreak is required. It is thus critical to obtain accurate information concerning the origin of the outbreak and its forward trajectory. However, there is often a lack of situational awareness that may lead to over- or under-reaction. There is a widening range of tests available for detecting pathogens, with typically different temporal characteristics, e.g. in terms of when peak test response occurs relative to time of exposure. We have developed a statistical framework that combines response level data from multiple diagnostic tests and is able to ‘hindcast’ (infer the historical trend of) an infectious disease epidemic. Assuming diagnostic test data from a cross-sectional sample of individuals infected with a pathogen during an outbreak, we use a Bayesian Markov Chain Monte Carlo (MCMC) approach to estimate time of exposure, and the overall epidemic trend in the population prior to the time of sampling. We evaluate the performance of this statistical framework on simulated data from epidemic trend curves and show that we can recover the parameter values of those trends. We also apply the framework to epidemic trend curves taken from two historical outbreaks: a bluetongue outbreak in cattle, and a whooping cough outbreak in humans. Together, these results show that hindcasting can estimate the time since infection for individuals and provide accurate estimates of epidemic trends, and can be used to distinguish whether an outbreak is increasing or past its peak. We conclude that if temporal characteristics of diagnostics are known, it is possible to recover epidemic trends of both human and animal pathogens from cross-sectional data collected at a single point in time

The Pathway Coexpression Network: Revealing pathway relationships.

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer's Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/

APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome

Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype