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This book translates the new findings in exercise research for the elderly for busy practitioners, trainees, students and administrators. This book provides practical strategies that can be implemented immediately in the common settings in which practitioners care for adults. The format includes key points and case examples which showcase the strong evidence supporting exercise by older adults as a key tool to enhance health, prevent serious outcomes, such as hospitalization and functional loss, and as part of the treatment plan for diseases that are common in older adults. Written by experts in the field of exercise in older persons, this book is a guide to maintaining quality of life and functional independence from frail to healthy aging adults. Strategies and exercises are discussed for specific care settings and illustrated via links to video examples, to ensure readers can immediately apply described techniques.Exercise for Aging Adults: A Guide for Practitioners is a useful tool for physicians, residents in training, medical students, physical therapists, gerontology advance practice nurse practitioners, assisted living facility administrators, directors of recreation, and long-term care directors.

This book translates the new findings in exercise research for the elderly for busy practitioners, trainees, students and administrators.This book provides practical strategies that can be implemented immediately in the common settings in which practitioners care for adults.

Older adults are at high risk for deconditioning as a result of bed rest during hospitalization.Deconditioning results in loss of function and discharge to higher levels of care, such as a nursing home, even after short or elective hospital stays.Older adults can participate in walking, resistance exercises, and early rehabilitation programs without increasing adverse events during acute hospitalization.Geriatric acute hospital units using comprehensive geriatric assessment, multidisciplinary teams, and interventions targeted to preserving function and mobility have the strongest evidence for reducing decline.Older adults for whom exercise may present significant risk or for whom exercise is not possible may benefit from passive range of motion and changes in position.System-wide interventions, such as changing the default activity order to out of bed, are recommended by experts yet require more study.

Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.The authors conducted a genetic meta-analysis of depression and found 269 associated genes. These genes highlight several potential drug repositioning opportunities, and relationships with depression were found for neuroticism and smoking.

Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified common risk variants which have progressively increased in number with increasing sample sizes of the respective studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank participants for three depression-related phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are significantly associated ( P  < 5 × 10 −8 ) across the three phenotypes. The direction of effect of these loci is consistently replicated in an independent sample, with 14 loci likely representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron spine and dendrite functions. Our findings suggest that broad depression is the most tractable UK Biobank phenotype for discovering genes and gene sets that further our understanding of the biological pathways underlying depression. The UK Biobank provides data for three depression-related phenotypes. Here, Howard et al. perform a genome-association study for broad depression, probable major depressive disorder (MDD) and hospital record-coded MDD in up to 322,580 UK Biobank participants which highlights excitatory synaptic pathways.

Assessing the Predictive Accuracy of QUICKI as a Surrogate Index for Insulin Sensitivity Using a Calibration Model Hui Chen , Gail Sullivan and Michael J. Quon From the Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland Address correspondence and reprint requests to Michael J. Quon, MD, PhD, Chief, Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Building 10, Room 6C-205, 10 Center Dr. MSC 1632, Bethesda, MD 20892-1632. E-mail: quonm{at}nih.gov Abstract The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear correlation with the glucose clamp index of insulin sensitivity (SI Clamp ) that is better than that of many other surrogate indexes. However, correlation between a surrogate and reference standard may improve as variability between subjects in a cohort increases (i.e., with an increased range of values). Correlation may be excellent even when prediction of reference values by the surrogate is poor. Thus, it is important to evaluate the ability of QUICKI to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In the present study, we used a calibration model to compare the ability of QUICKI and other simple surrogates to predict SI Clamp . Predictive accuracy was evaluated by both root mean squared error of prediction as well as a more robust leave-one-out cross-validation–type root mean squared error of prediction (CVPE). Based on data from 116 glucose clamps obtained from nonobese, obese, type 2 diabetic, and hypertensive subjects, we found that QUICKI and log (homeostasis model assessment [HOMA]) were both excellent at predicting SI Clamp (CVPE = 1.45 and 1.51, respectively) and significantly better than HOMA, 1/HOMA, and fasting insulin (CVPE = 3.17, P < 0.001; 1.67, P < 0.02; and 2.85, P < 0.001, respectively). QUICKI and log(HOMA) also had the narrowest distribution of residuals (measured SI Clamp − predicted SI Clamp ). In a subset of subjects ( n = 78) who also underwent a frequently sampled intravenous glucose tolerance test with minimal model analysis, QUICKI was significantly better than the minimal model index of insulin sensitivity (SI MM ) at predicting SI Clamp (CVPE = 1.54 vs. 1.98, P = 0.001). We conclude that QUICKI and log(HOMA) are among the most accurate surrogate indexes for determining insulin sensitivity in humans. CVPE, cross-validation–type root mean squared error of prediction FSIVGTT, frequently sampled intravenous glucose tolerance test HOMA, homeostasis model assessment QUICKI, quantitative insulin-sensitivity check index RMSE, square root of the mean squared error of prediction Footnotes Accepted April 4, 2005. Received September 11, 2004. DIABETES

A genetic synthetic lethal screen reveals that ATM and MET kinases promote cell survival upon activation of p53 with Nutlin-3, and these survival pathways act in parallel to canonical cell cycle arrest and apoptotic genes induced by p53. The p53 tumor suppressor orchestrates alternative stress responses including cell cycle arrest and apoptosis, but the mechanisms defining cell fate upon p53 activation are poorly understood. Several small-molecule activators of p53 have been developed, including Nutlin-3, but their therapeutic potential is limited by the fact that they induce reversible cell cycle arrest in most cancer cell types. We report here the results of a genome-wide short hairpin RNA screen for genes that are lethal in combination with p53 activation by Nutlin-3, which showed that the ATM and MET kinases govern cell fate choice upon p53 activation. Genetic or pharmacological interference with ATM or MET activity converts the cellular response from cell cycle arrest into apoptosis in diverse cancer cell types without affecting expression of key p53 target genes. ATM and MET inhibitors also enable Nutlin-3 to kill tumor spheroids. These results identify new pathways controlling the cellular response to p53 activation and aid in the design of p53-based therapies.