Emotional and motivational pain processing : current state of knowledge and perspectives in translational research

Pain elicits fear and anxiety and promotes escape, avoidance, and adaptive behaviors that are essential for survival. When pain persists, motivational priority and attention shift to pain-related information. Such a shift often results in impaired functionality, leading to maladaptive pain-related fear and anxiety and escape and avoidance behaviors. Neuroimaging studies in chronic pain patients have established that brain activity, especially in cortical and mesolimbic regions, is different from activity observed during acute pain in control subjects. In this review, we discuss the psychophysiological and neuronal factors that may be associated with the transition to chronic pain. We review information from human studies on neural circuits involved in emotional and motivational pain processing and how these circuits are altered in chronic pain conditions. We then highlight findings from animal research that can increase our understanding of the molecular and cellular mechanisms underlying emotional-motivational pain processing in the brain. Finally, we discuss how translational approaches incorporating results from both human and animal investigations may aid in accelerating the discovery of therapies

Environmental Factors Affecting the Expression of pilAB as Well as the Proteome and Transcriptome of the Grass Endophyte Azoarcus sp. Strain BH72

gene encoding the structural protein of type IV pili that are essential for plant colonization appears to be regulated in a population density-dependent manner.. The expression of one of them was shown to be induced in plant roots. sp. to analyze mechanisms and molecules involved in the population-dependent gene expression in this endophyte in future

Computer-assisted mitotic count using a deep learning–based algorithm improves interobserver reproducibility and accuracy

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, computer-assisted review by pathologists may ensure reliability. In the present study, we compared partial (MC-ROI preselection) and full (additional visualization of MF candidates and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole-slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MFs, and improving classification against imposters. The interobserver consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected hotspot MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study demonstrate that computer assistance may lead to more reproducible and accurate MCs in ccMCTs

Statistical methods for body mass index: a selective review

Obesity rates have been increasing over recent decades, causing significant concern among policy makers. Excess body fat, commonly measured by body mass index, is a major risk factor for several common disorders including diabetes and cardiovascular disease, placing a substantial burden on health care systems. To guide effective public health action, we need to understand the complex system of intercorrelated influences on body mass index. This paper, based on all eligible articles searched from Global health, Medline and Web of Science databases, reviews both classical and modern statistical methods for body mass index analysis. We give a description of each of these methods, exploring the classification, links and differences between them and the reasons for choosing one over the others in different settings. We aim to provide a key resource and statistical library for researchers in public health and medicine to deal with obesity and body mass index data analysis.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work has been supported in part by the National Institute for Health Research Method Grant (NIHR RMOFS-2013-03-09) and the National Natural Science Foundation of China (Grant No. 71490725, 11261048, 11371322)

Genes that determine immunology and inflammation modify the basic defect of impaired ion conductance in cystic fibrosis epithelia

BACKGROUND: The cystic fibrosis (CF) basic defect, caused by dysfunction of the apical chloride channel CFTR in the gastrointestinal and respiratory tract epithelia, has not been employed so far to support the role of CF modifier genes. METHODS: Patients were selected from 101 families with a total of 171 F508del-CFTR homozygous CF patients to identify CF modifying genes. A candidate gene based association study of 52 genes on 16 different chromosomes with a total of 182 genetic markers was performed. Differences in haplotype and/or diplotype distribution between case and reference CF subpopulations were analysed. RESULTS: Variants at immunologically relevant genes were associated with the manifestation of the CF basic defect (0.01<Praw<0.0001 at IL1B, TLR9, TNFalpha, CD95, STAT3 and TNFR). The intragenic background of F508del-CFTR chromosomes determined disease severity and manifestation of the basic defect (Praw=0.0009). Allele distributions comparing transmitted and non-transmitted alleles were distorted at several loci unlinked to CFTR. CONCLUSIONS: The inherited capabilities of the innate and adaptive immune system determine the manifestation of the CF basic defect. Variants on F508del-CFTR chromosomes contribute to the observed patient-to-patient variability among F508del-CFTR homozygotes. A survivor effect, manifesting as a transmission disequilibrium at many loci, is consistent with the improvement of clinical care over the last decades, resulting in a depletion of risk alleles at modifier genes. Awareness of non-genetic factors such as improvement of patient care over time is crucial for the interpretation of CF modifier studies

Economic evaluation of surgical treatments for women with stress urinary incontinence : a cost-utility and value of information analysis

Acknowledgements: We would like to acknowledge all those involved in the wider study exploring the effectiveness and cost-effectiveness of surgical treatments for women with stress urinary incontinence. Funding: This research was commissioned by the NIHR HTA Programme as project number 15/09/06. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design, collection, analysis and interpretation of data, the writing of the manuscript and the decision to submit it for publication were all performed independent of the funders.Peer reviewedPublisher PD

Surgical treatments for women with stress urinary incontinence : the ESTER systematic review and economic evaluation

Funded by The National Institute for Health Research Health Technology Assessment programme.Peer reviewedPublisher PD

Surgical interventions for women with stress urinary incontinence : systematic review and network meta-analysis of randomised controlled trials

Funding: This project was funded by the NIHR HTA programme (project No 15/09/06). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design; collection, analysis, and interpretation of data; writing of the manuscript; and decision to submit it for publication were performed independent of the funders.Peer reviewedPublisher PD