Alien Registration- Savage, Jennie S. (Houlton, Aroostook County)

https://digitalmaine.com/alien_docs/34828/thumbnail.jp

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Whole-genome sequence-based analysis of thyroid function

Tiina Paunio on työryhmän UK10K Consortium jäsen.Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N = 2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF >= 1%) associated with TSH and FT4 (N = 16,335). For TSH, we identify a novel variant in SYN2 (MAF = 23.5%, P = 6.15 x 10(-9)) and a new independent variant in PDE8B (MAF = 10.4%, P = 5.94 x 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/ SLC25A52 (MAF = 3.2%, P = 1.27 x 10(-9)) tagging a rare TTR variant (MAF = 0.4%, P = 2.14 x 10(-11)). All common variants explain >= 20% of the variance in TSH and FT4. Analysis of rare variants (MAFPeer reviewe

Alien Registration- Savage, Jennie S. (Houlton, Aroostook County)

https://digitalmaine.com/alien_docs/34828/thumbnail.jp

Emergency Department Communication in Persons Living With Dementia and Care Partners: A Scoping Review

OBJECTIVES: To synthesize published research exploring emergency department (ED) communication strategies and decision-making with persons living with dementia (PLWD) and their care partners as the basis for a multistakeholder consensus conference to prioritize future research. DESIGN: Systematic scoping review. SETTINGS AND PARTICIPANTS: PLWD and their care partners in the ED setting. METHODS: Informed by 2 Patient-Intervention-Comparison-Outcome (PICO) questions, we conducted systematic electronic searches of medical research databases for relevant publications following standardized methodological guidelines. The results were presented to interdisciplinary stakeholders, including dementia researchers, clinicians, PLWD, care partners, and advocacy organizations. The PICO questions included: How does communication differ for PLWD compared with persons without dementia? Are there specific communication strategies that improve the outcomes of ED care? Future research areas were prioritized. RESULTS: From 5451 studies identified for PICO-1, 21 were abstracted. From 2687 studies identified for PICO-2, 3 were abstracted. None of the included studies directly evaluated communication differences between PLWD and other populations, nor the effectiveness of specific communication strategies. General themes emerging from the scoping review included perceptions by PLWD/care partners of rushed ED communication, often exacerbated by inconsistent messages between providers. Care partners consistently reported limited engagement in medical decision-making. In order, the research priorities identified included: (1) Barriers/facilitators of effective communication; (2) valid outcome measures of effective communication; (3) best practices for care partner engagement; (4) defining how individual-, provider-, and system-level factors influence communication; and (5) understanding how each member of ED team can ensure high-quality communication. CONCLUSIONS AND IMPLICATIONS: Research exploring ED communication with PLWD is sparse and does not directly evaluate specific communication strategies. Defining barriers and facilitators of effective communication was the highest-ranked research priority, followed by validating outcome measures associated with improved information exchange

Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy

Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electrocardiography, transthoracic echocardiography and microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural and functional cardiac abnormalities, here we identify 705 lines with cardiac arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these 705 genes, 486 have not been previously associated with cardiac dysfunction in humans, and some of them represent variants of unknown relevance (VUR). Mice with mutations in Casz1, Dnajc18, Pde4dip, Rnf38 or Tmem161b genes show developmental cardiac structural abnormalities, with their human orthologs being categorized as VUR. Using UK Biobank data, we validate the importance of the DNAJC18 gene for cardiac homeostasis by showing that its loss of function is associated with altered left ventricular systolic function. Our results identify hundreds of previously unappreciated genes with potential function in congenital heart disease and suggest causal function of five VUR in congenital heart disease

Emergency Department Care Transitions for Patients With Cognitive Impairment: A Scoping Review

ObjectivesWe aimed to describe emergency department (ED) care transition interventions delivered to older adults with cognitive impairment, identify relevant patient-centered outcomes, and determine priority research areas for future investigation.DesignSystematic scoping review.Setting and participantsED patients with cognitive impairment and/or their care partners.MethodsInformed by the clinical questions, we conducted systematic electronic searches of medical research databases for relevant publications following published guidelines. The results were presented to a stakeholder group representing ED-based and non-ED-based clinicians, individuals living with cognitive impairment, care partners, and advocacy organizations. After discussion, they voted on potential research areas to prioritize for future investigations.ResultsFrom 3848 publications identified, 78 eligible studies underwent full text review, and 10 articles were abstracted. Common ED-to-community care transition interventions for older adults with cognitive impairment included interdisciplinary geriatric assessments, home visits from medical personnel, and telephone follow-ups. Intervention effects were mixed, with improvements observed in 30-day ED revisit rates but most largely ineffective at promoting connections to outpatient care or improving secondary outcomes such as physical function. Outcomes identified as important to adults with cognitive impairment and their care partners included care coordination between providers and inclusion of care partners in care management within the ED setting. The highest priority research area for future investigation identified by stakeholders was identifying strategies to tailor ED-to-community care transitions for adults living with cognitive impairment complicated by other vulnerabilities such as social isolation or economic disadvantage.Conclusions and implicationsThis scoping review identified key gaps in ED-to-community care transition interventions delivered to older adults with cognitive impairment. Combined with a stakeholder assessment and prioritization, it identified relevant patient-centered outcomes and clarifies priority areas for future investigation to improve ED care for individuals with impaired cognition, an area of critical need given the current population trends

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P &lt; 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p