Transcriptome profiling of immune responses to cardiomyopathy syndrome (CMS) in Atlantic salmon

<p>Abstract</p> <p>Background</p> <p>Cardiomyopathy syndrome (CMS) is a disease associated with severe myocarditis primarily in adult farmed Atlantic salmon (<it>Salmo salar </it>L.), caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV) with structural similarities to the <it>Totiviridae </it>family. Here we present the first characterisation of host immune responses to CMS assessed by microarray transcriptome profiling.</p> <p>Results</p> <p>Unvaccinated farmed Atlantic salmon post-smolts were infected by intraperitoneal injection of PMCV and developed cardiac pathology consistent with CMS. From analysis of heart samples at several time points and different tissues at early and clinical stages by oligonucleotide microarrays (SIQ2.0 chip), six gene sets representing a broad range of immune responses were identified, showing significant temporal and spatial regulation. Histopathological examination of cardiac tissue showed myocardial lesions from 6 weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery. Viral RNA was detected in all organs from 4 wpi suggesting a broad tissue tropism. High correlation between viral load and cardiac histopathology score suggested that cytopathic effect of infection was a major determinant of the myocardial changes. Strong and systemic induction of antiviral and IFN-dependent genes from 2 wpi that levelled off during infection, was followed by a biphasic activation of pathways for B cells and MHC antigen presentation, both peaking at clinical pathology. This was preceded by a distinct cardiac activation of complement at 6 wpi, suggesting a complement-dependent activation of humoral Ab-responses. Peak of cardiac pathology and viral load coincided with cardiac-specific upregulation of T cell response genes and splenic induction of complement genes. Preceding the reduction in viral load and pathology, these responses were probably important for viral clearance and recovery.</p> <p>Conclusions</p> <p>By comparative analysis of gene expression, histology and viral load, the temporal and spatial regulation of immune responses were characterised and novel immune genes identified, ultimately leading to a more complete understanding of host-virus responses and pathology and protection in Atlantic salmon during CMS.</p

Parental alcohol use and adolescent school adjustment in the general population: Results from the HUNT study

<p>Abstract</p> <p>Background</p> <p>This study investigates the relationship between parental drinking and school adjustment in a total population sample of adolescents, with independent reports from mothers, fathers, and adolescents. As a group, children of alcohol abusers have previously been found to exhibit lowered academic achievement. However, few studies address which parts of school adjustment that may be impaired. Both a genetic approach and social strains predict elevated problem scores in these children. Previous research has had limitations such as only recruiting cases from clinics, relying on single responders for all measures, or incomplete control for comorbid psychopathology. The specific effects of maternal and paternal alcohol use are also understudied.</p> <p>Methods</p> <p>In a Norwegian county, 88% of the population aged 13-19 years participated in a health survey (N = 8984). Among other variables, adolescents reported on four dimensions of school adjustment, while mothers and fathers reported their own drinking behaviour. Mental distress and other control variables were adjusted for. Multivariate analysis including generalized estimation equations was applied to investigate associations.</p> <p>Results</p> <p>Compared to children of light drinkers, children of alcohol abusers had moderately elevated attention and conduct problem scores. Maternal alcohol abuse was particularly predictive of such problems. Children of abstainers did significantly better than children of light drinkers. Controlling for adolescent mental distress reduced the association between maternal abuse and attention problems. The associations between parental reported drinking and school adjustment were further reduced when controlling for the children's report of seeing their parents drunk, which itself predicted school adjustment. Controlling for parental mental distress did not reduce the associations.</p> <p>Conclusions</p> <p>Parental alcohol abuse is an independent risk factor for attention and conduct problems at school. Some of the risk associated with mothers' drinking is likely to be mediated by adolescent mental distress. Despite lowered adjustment on the externalizing dimensions, children of alcohol abusers report that they enjoy being at school as much as other children.</p

Subclonal diversification of primary breast cancer revealed by multiregion sequencing.

The sequencing of cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer

Pregnancy-related pelvic girdle pain: an update

A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women