Genetic Insulin Resistance Is a Potent Regulator of Gene Expression and Proliferation in Human iPS Cells

Insulin resistance is central to diabetes and metabolic syndrome. To define the consequences of genetic insulin resistance distinct from those secondary to cellular differentiation or in vivo regulation, we generated induced pluripotent stem cells (iPSCs) from individuals with insulin receptor mutations and age-appropriate control subjects and studied insulin signaling and gene expression compared with the fibroblasts from which they were derived. iPSCs from patients with genetic insulin resistance exhibited altered insulin signaling, paralleling that seen in the original fibroblasts. Insulin-stimulated expression of immediate early genes and proliferation were also potently reduced in insulin resistant iPSCs. Global gene expression analysis revealed marked differences in both insulin-resistant iPSCs and corresponding fibroblasts compared with control iPSCs and fibroblasts. Patterns of gene expression in patients with genetic insulin resistance were particularly distinct in the two cell types, indicating dependence on not only receptor activity but also the cellular context of the mutant insulin receptor. Thus, iPSCs provide a novel approach to define effects of genetically determined insulin resistance. This study demonstrates that effects of insulin resistance on gene expression are modified by cellular context and differentiation state. Moreover, altered insulin receptor signaling and insulin resistance can modify proliferation and function of pluripotent stem cell populations.     

Sleep spindle detection using multivariate Gaussian mixture models

In this research study we have developed a clustering‐based automatic sleep spindle detection method that was evaluated on two different databases. The databases consisted of 20 all‐night polysomnograph recordings. Past detection methods have been based on subject‐independent and some subject‐dependent parameters, such as fixed or variable thresholds to identify spindles. Using a multivariate Gaussian mixture model clustering technique, our algorithm was developed to use only subject‐specific parameters to detect spindles. We have obtained an overall sensitivity range (65.1–74.1%) at a (59.55–119.7%) false positive proportion.     

Nursing Case Management Strategies for Adults with Serious Mental Illness Seeking Dental Services

A university-community partnership initiated a dental screening and nursing case management program for Medicaid-insured adults with serious mental illness (SMI). Forty-three adults with SMI participated in dental screening; 72% participated in case management. Per client, an average of six case management contacts was made. After 6 months, 87% (27/31) had attended at least one dental appointment, with a 13% no-show rate; 8 completed treatment, 4 had ongoing treatment, 12 had interrupted care, and 3 were lost to follow-up. Adults with SMI experienced high unmet dental needs; nursing case management strategies aided clients to initiate and complete dental care.     

Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia

Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide–induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease.     

Social work‐generated evidence in traumatic brain injury from 1975 to 2014: A systematic scoping review

The International Network for Social Workers in Acquired Brain Injury (INSWABI) commissioned a systematic scoping review to ascertain the social work‐generated evidence base on people with traumatic brain injury (TBI) of working age. The review aimed to identify the output, impact and quality of publications authored by social workers on this topic. Study quality was evaluated through assessment frameworks drawn from the United Kingdom National Service Framework for Long‐Term Conditions. In the 40‐year period from 1975 to 2014, 115 items were published that met the search criteria (intervention studies, n = 10; observational studies, n = 52; literature reviews, n = 6; expert opinion or policy analysis, n = 39; and others, n = 8). The publications could be grouped into five major fields of practice: families, social inclusion, military, inequalities and psychological adjustment. There was a significant increase in the number of publications over each decade. Impact was demonstrated in that the great majority of publications had been cited at least once (80.6%, 103/115). Articles published in rehabilitation journals were cited significantly more often than articles published in social work journals. A significant improvement in publication quality was observed across the four decades, with the majority of studies in the last decade rated as high quality.