Screening Tools for Alcohol Use Disorder Among Older Adults: A Scoping Review.

Purpose: As the number of older adults increases, the volume of alcohol-related problems among the older adult population also rises. The purpose of the current scoping review was to summarize and disseminate research findings related to screening for alcohol use disorder (AUD) in older adults (aged ≥60 years) and determine if research gaps exist in the current literature.

Method: The concepts of older adults, screening tools, AUD, and instrument evaluation were searched in Medline, APA PsycINFO, and CINAHL.

Sleep Quality and Interoception Are Associated with Generalized Anxiety in Baccalaureate Nursing Students: A Cross-Sectional Study.

Baccalaureate nursing students are at increased risk for anxiety and related mood disorders. We conducted a cross-sectional study to explore the relationships among anxiety symptoms measured by the Generalized Anxiety Disorder (GAD-7) questionnaire and lifestyle behaviors including habitual diet, sleep quality (Pittsburg Sleep Quality Index [PSQI]), and physical activity. Descriptive statistics were obtained for sample characteristics, and Pearson correlations and backward stepwise linear regression explored relationships between the GAD-7 scores, the Multidimensional Assessment of Interoceptive Awareness, version 2 (MAIA-2) subscales, and other variables.

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease at High Risk of Exacerbation: The BICS Randomized Clinical Trial.

Importance: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that β-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission.

Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.

Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study.

Background: Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH.

EyeG2P: an automated variant filtering approach improves efficiency of diagnostic genomic testing for inherited ophthalmic disorders.

Background: Genomic variant prioritisation is one of the most significant bottlenecks to mainstream genomic testing in healthcare. Tools to improve precision while ensuring high recall are critical to successful mainstream clinical genomic testing, in particular for whole genome sequencing where millions of variants must be considered for each patient.

Methods: We developed EyeG2P, a publicly available database and web application using the Ensembl Variant Effect Predictor.

Genetic and chemotherapeutic influences on germline hypermutation.

Mutations in the germline generates all evolutionary genetic variation and is a cause of genetic disease. Parental age is the primary determinant of the number of new germline mutations in an individual's genome. Here we analysed the genome-wide sequences of 21,879 families with rare genetic diseases and identified 12 individuals with a hypermutated genome with between two and seven times more de novo single-nucleotide variants than expected.

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS).

Background: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations.

Impact of Parental Illness and Injury on Pediatric Disorders of Gut-Brain Interaction.

Objective: To evaluate the relationship between parental injury and illness and disorders of gut-brain interaction (DGBI) in children.

Study Design: A self-controlled case series using data from the Military Health System Data Repository compared International Classification of Diseases, Ninth Revision-identified DGBI-related outpatient visits and prescriptions in 442 651 children aged 3-16 years in the 2 years before and the 2 years after the injury and/or illness of their military parent. Negative binomial regression was used to compare visit rates for constipation, fecal incontinence, abdominal pain, irritable bowel syndrome, and a composite of these before and after parental injury and/or illness.

Evidence for 28 genetic disorders discovered by combining healthcare and research data.

De novo mutations in protein-coding genes are a well-established cause of developmental disorders. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations. Here, to identify previously undescribed genes associated with developmental disorders, we integrate healthcare and research exome-sequence data from 31,058 parent-offspring trios of individuals with developmental disorders, and develop a simulation-based statistical test to identify gene-specific enrichment of de novo mutations.

Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders.

How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis.

Contribution of retrotransposition to developmental disorders.

Mobile genetic Elements (MEs) are segments of DNA which can copy themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. Here we identify RT-derived events in 9738 exome sequenced trios with DD-affected probands.

The University of São Paulo Twin Panel: Current Status and Prospects for Brazilian Twin Studies in Behavioral Research.

The University of São Paulo Twin Panel (Painel USP de Gêmeos), based at the Institute of Psychology of the University of São Paulo, started formally in 2017. Our registry is new, but in only two years of formal existence, it comprises a volunteer sample of 4826 registered individuals (98% twins and 2% higher-order multiples), recruited at the University of São Paulo and by social media campaigns. Our main aim is to conduct and promote research with twins on psychological processes and behavior.

Analyzing Hospital Choices of Colon Cancer Patients in Four States in Appalachia.

While geographic disparities in cancer treatment are documented, little research has investigated patients' willingness to travel longer distances for treatment at higher-quality hospitals. Even fewer studies have compared metropolitan and non-metropolitan patients on this dimension. Using population-based data from the Appalachian counties of four states, we identified all hospitals within a plausible driving distance of each newly diagnosed colon cancer patient and estimated conditional logit models of hospital choices for cancer surgery.

Pathogenicity and selective constraint on variation near splice sites.

Mutations that perturb normal pre-mRNA splicing are significant contributors to human disease. We used exome sequencing data from 7833 probands with developmental disorders (DDs) and their unaffected parents, as well as more than 60,000 aggregated exomes from the Exome Aggregation Consortium, to investigate selection around the splice sites and quantify the contribution of splicing mutations to DDs. Patterns of purifying selection, a deficit of variants in highly constrained genes in healthy subjects, and excess de novo mutations in patients highlighted particular positions within and around the consensus splice site of greater functional relevance.

Quantifying the contribution of recessive coding variation to developmental disorders.

We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations.

De novo mutations in regulatory elements in neurodevelopmental disorders.

We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders.

Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD.

Background: Beta-blockers remain underused in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease.

Aim: We compared how different inhaled therapies affect tolerability of bisoprolol and carvedilol in moderate to severe COPD.

Design: A randomized, open label, cross-over study.

Thyrotoxicosis and Choledocholithiasis Masquerading as Thyroid Storm.

A 26-year-old female, thirteen months postpartum, presented to the emergency department for four weeks of epigastric abdominal pain, pruritus, new onset jaundice, and 11.3 kgs (25 lbs) unintentional weight loss. On examination, she was afebrile, tachycardic, alert, and oriented and had jaundice with scleral icterus.

Tunable Surface Repellency Maintains Stemness and Redox Capacity of Human Mesenchymal Stem Cells.

Human bone marrow derived mesenchymal stem cells (hMSCs) hold great promise for regenerative medicine due to their multipotent differentiation capacity and immunomodulatory capabilities. Substantial research has elucidated mechanisms by which extracellular cues regulate hMSC fate decisions, but considerably less work has addressed how material properties can be leveraged to maintain undifferentiated stem cells. Here, we show that synthetic culture substrates designed to exhibit moderate cell-repellency promote high stemness and low oxidative stress-two indicators of naïve, healthy stem cells-in commercial and patient-derived hMSCs.

Design and use of mouse control DNA for DNA biomarker extraction and PCR detection from urine: Application for transrenal Mycobacterium tuberculosis DNA detection.

Urine samples are increasingly used for diagnosing infections including Escherichia coli, Ebola virus, and Zika virus. However, extraction and concentration of nucleic acid biomarkers from urine is necessary for many molecular detection strategies such as polymerase chain reaction (PCR). Since urine samples typically have large volumes with dilute biomarker concentrations making them prone to false negatives, another impediment for urine-based diagnostics is the establishment of appropriate controls particularly to rule out false negatives.

Inhaled corticosteroid dose response in asthma: Should we measure inflammation?

Background: Inhaled corticosteroid (ICS) titration in asthma is primarily based on symptoms and pulmonary function. ICSs may not be increased on this basis despite residual airway inflammation.

Objective: To compare the dose-response relationships of ICSs on measures of pulmonary function, symptoms, and inflammation in patients with persistent asthma.

Is Gly16Arg β2 Receptor Polymorphism Related to Impulse Oscillometry in a Real-Life Asthma Clinic Setting?

Purpose: We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting.

Methods: Patients with persistent asthma taking inhaled corticosteroid ± long-acting beta-agonist (ICS ± LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.