Iatrogenic Intraoperative Fracture in Patients With Osteogenesis Imperfecta.

Background: Osteogenesis imperfecta (OI) is a genetic defect in collagen type I, phenotypically characterized by bony fragility and a propensity to high rates of childhood fracture. Fragility fractures in patients with OI have been reported with routine hospital care. In addition, there is a nonzero rate of iatrogenic fracture during orthopaedic surgery directly related to the technical steps of the procedure itself.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium.

The impact of damaging epilepsy and cardiac genetic variant burden in sudden death in the young.

Background: Sudden unexpected death in children is a tragic event. Understanding the genetics of sudden death in the young (SDY) enables family counseling and cascade screening. The objective of this study was to characterize genetic variation in an SDY cohort using whole genome sequencing.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies as a candidate in PLS.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 30,000 people in the United States. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease.

Screening cut-off scores for clinically significant fatigue in early Parkinson's disease.

Background: Fatigue is one of the most disabling non-motor symptoms in PD. Researchers have previously used cut-offs validated in non-PD conditions when using the Fatigue Severity Scale (FSS) or the Multidimensional Fatigue Inventory (MFI) scores to evaluate fatigue in PD.

Objective: We used a set of criteria for diagnosing clinically significant fatigue in PD to identify the proper cut-offs of the FSS and MFI.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies as a candidate in PLS.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 30,000 people in the United States. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease.

Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans.

Background: Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations.

Methods: New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction.

The impact of damaging epilepsy and cardiac genetic variant burden in sudden death in the young.

Background: Sudden unexpected death in children is a tragic event. Understanding the genetics of sudden death in the young (SDY) enables family counseling and cascade screening. The objective of this study was to characterize genetic variation in an SDY cohort using whole genome sequencing.

Genomic Autopsy of Sudden Deaths in Young Individuals.

Importance: Postmortem genetic testing of young individuals with sudden death has previously identified pathogenic gene variants. However, prior studies primarily considered highly penetrant monogenic variants, often without detailed decedent and family clinical information.

Objective: To assess genotype and phenotype risk in a diverse cohort of young decedents with sudden death and their families.

Exome sequencing in obsessive-compulsive disorder reveals a burden of rare damaging coding variants.

Obsessive-compulsive disorder (OCD) affects 1-2% of the population, and, as with other complex neuropsychiatric disorders, it is thought that rare variation contributes to its genetic risk. In this study, we performed exome sequencing in the largest OCD cohort to date (1,313 total cases, consisting of 587 trios, 41 quartets and 644 singletons of affected individuals) and describe contributions to disease risk from rare damaging coding variants. In case-control analyses (n = 1,263/11,580), the most significant single-gene result was observed in SLITRK5 (odds ratio (OR) = 8.

Genomic Context Differs Between Human Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy.

Background Inherited cardiomyopathies display variable penetrance and expression, and a component of phenotypic variation is genetically determined. To evaluate the genetic contribution to this variable expression, we compared protein coding variation in the genomes of those with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Methods and Results Nonsynonymous single-nucleotide variants (nsSNVs) were ascertained using whole genome sequencing from familial cases of HCM (n=56) or DCM (n=70) and correlated with echocardiographic information.

Association of cardiovascular health and epigenetic age acceleration.

Background: Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the "Life's Simple 7" ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality.

Genetic Variation in Enhancers Modifies Cardiomyopathy Gene Expression and Progression.

Background: Inherited cardiomyopathy associates with a range of phenotypes, mediated by genetic and nongenetic factors. Noninherited cardiomyopathy also displays varying progression and outcomes. Expression of cardiomyopathy genes is under the regulatory control of promoters and enhancers, and human genetic variation in promoters and enhancers may contribute to this variability.

Saprolegnia infection after vaccination in Atlantic salmon is associated with differential expression of stress and immune genes in the host.

This study assessed the impact of routine vaccination of Atlantic salmon pre-smolts on gene expression and the possible link to saprolegniosis on Scottish fish farms. Fish were in 4 different groups 1) 'control' - fish without handling or vaccination 2) 'vaccinated' - fish undergoing full vaccination procedure 3) 'non vaccinated' - fish undergoing full vaccination procedure but not vaccinated and 4) 'vaccinated-MH' - fish undergoing vaccination, but procedure involved minimal handling. A strong increase in cortisol and glucose levels was observed after 1 h in all groups relative to the control group.

Pathogenic and Uncertain Genetic Variants Have Clinical Cardiac Correlates in Diverse Biobank Participants.

Background Genome sequencing coupled with electronic heath record data can uncover medically important genetic variation. Interpretation of rare genetic variation and its role in mediating cardiovascular phenotypes is confounded by variants of uncertain significance. Methods and Results We analyzed the whole genome sequence of 900 racially and ethnically diverse biobank participants selected from a single US center.

Corticosterone mediates telomere length in raptor chicks exposed to chemical mixture.

Stressors experience early in life by animals may have carry over impacts on life-traits over the life cycle. Accelerated telomere attrition induced by stress during development and growth could play a role in such delayed effects. Among stressors, exposure to chemicals may modify telomere dynamic but, to date, the trends evidenced between exposure and telomere shortening remains inconsistent.

Immunoassays are not immune to errors: Examples from two studies of steroid output from freshwater trout farms.

A "reproducibility crisis" is widespread across scientific disciplines, where results and conclusions of studies are not supported by subsequent investigation. Here we provide a steroid immunoassay example where human errors generated unreproducible results and conclusions. Our study was triggered by a scientific report citing abnormally high concentrations (means of 4-79 ng L) of three natural sex steroids [11-ketotestosterone (11-KT), testosterone (T) and oestradiol (E2)] in water samples collected from two UK rivers over 4 years (2002-6).

Effects of temperature on amoebic gill disease development: Does it play a role?

A relationship between increasing water temperature and amoebic gill disease (AGD) prevalence in Atlantic salmon (Salmo salar) has been noted at fish farms in numerous countries. In Scotland (UK), temperatures above 12°C are considered to be an important risk factor for AGD outbreaks. Thus, the purpose of this study was to test for the presence of an association between temperature and variation in the severity of AGD in Atlantic salmon at 10 and 15°C.

Effects of brownification and warming on algal blooms, metabolism and higher trophic levels in productive shallow lake mesocosms.

An increase of dissolved organic carbon (DOC) in inland waters has been reported across the northern temperate region but the effects of this on whole lake ecosystems, often combined with other anthropogenic stressors like nutrient inputs and warming, are poorly known. The effects of these changes on different component of the ecosystem were assessed in an experiment using twenty-four large (3000L) outdoor mesocosms simulating shallow lakes. Two different temperature regimes (ambient and ambient +4 °C) combined with three levels of organic matter (OM, added as filtered peaty water), simulating the DOC increase that is predicted to take place over the next 4 to 21 years were used.

Meta-analysis of exome array data identifies six novel genetic loci for lung function.

Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV ), forced vital capacity (FVC) and the ratio of FEV to FVC (FEV /FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals.

Effectiveness of a multidisciplinary patient care bundle for reducing surgical-site infections.

Background: Surgical-site infection (SSI) is associated with significant healthcare costs. To reduce the high rate of SSI among patients undergoing colorectal surgery at a cancer centre, a comprehensive care bundle was implemented and its efficacy tested.

Methods: A pragmatic study involving three phases (baseline, implementation and sustainability) was conducted on patients treated consecutively between 2013 and 2016.

The Influence of Sex, Parasitism, and Ontogeny on the Physiological Response of European Eels (Anguilla anguilla) to an Abiotic Stressor.

Migration of adult European eels (Anguilla anguilla) from freshwater feeding grounds to oceanic spawning grounds is an energetically demanding process and is accompanied by dramatic physiological and behavioral changes. Humans have altered the aquatic environment (e.g.