A Web-Based, Population-Based Cirrhosis Identification and Management System for Improving Cirrhosis Care: Qualitative Formative Evaluation.

Background: Cirrhosis, or scarring of the liver, is a debilitating condition that affects millions of US adults. Early identification, linkage to care, and retention of care are critical for preventing severe complications and death from cirrhosis.

Objective: The purpose of this study is to conduct a preimplementation formative evaluation to identify factors that could impact implementation of the Population-Based Cirrhosis Identification and Management System (P-CIMS) in clinics serving patients with cirrhosis.

Neoliberalism and Accountability Failure in the Delivery of Services Affecting the Health of the Public.

Since the 1980s, the emergence of neoliberalism as a dominant government paradigm has led to increasing instances of accountability failure, resulting in significant injuries or death. Employing a grounded theory approach, accountability failure is defined and explored through analysis of 18 public inquiries and reports in the United Kingdom and Canada. The analysis reveals that the combination of a neoliberal policy paradigm and flawed regulation, governance, culture, and performance management inevitably led to accountability failure.

Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington's disease mice.

Huntington's disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD.

Improving the Electronic Capture of Advance Care Directives in a Healthcare Delivery System.

Objectives: To determine the effectiveness of a multifaceted quality improvement intervention in outpatient clinics at an integrated healthcare delivery system on capture rate of advance directives (ADs) in the electronic medical record (EMR).

Design: Interrupted time series analysis with control groups between January 2010 and June 2015.

Setting: Oncology, nephrology, and primary care outpatient clinics in an integrated healthcare delivery system.

Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific.

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions could be present in all brain cells. The effects of nuclear inclusion formation have been mainly studied in neurons, while the effect on glia has been comparatively disregarded.

Collaborative Care for Depression in Chronic Hepatitis C Clinics.

Objective: Depression is highly prevalent yet underdiagnosed and undertreated among patients with chronic hepatitis C virus (HCV) infection. Collaborative care models have improved depression outcomes in primary care settings, and this study aimed to provide more information on testing such methods in specialty HCV care.

Methods: Hepatitis C Translating Initiatives for Depression Into Effective Solutions (HEPTIDES) was a randomized controlled trial that tested a collaborative depression care model in HCV clinics at four Veterans Affairs facilities.

Correction: SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice.

[This corrects the article DOI: 10.1371/journal.pone.

SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice.

Huntington's disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown.

Qualitative analysis of patient-centered decision attributes associated with initiating hepatitis C treatment.

Background: In this era of a constantly changing landscape of antiviral treatment options for chronic viral hepatitis C (CHC), shared clinical decision-making addresses the need to engage patients in complex treatment decisions. However, little is known about the decision attributes that CHC patients consider when making treatment decisions. We identify key patient-centered decision attributes, and explore relationships among these attributes, to help inform the development of a future CHC shared decision-making aid.

Transforming Ward Rounds Through Rounding-in-Flow.

Background: Traditional "batched" bedside clinical care rounds, where rounds for all patients precede clinical tasks, may delay clinical care and reduce resident work efficiency.

Innovation: Using Lean concepts, we developed a novel "Rounding-in-Flow" approach, with the patient care team completing all tasks for a single patient before initiating any tasks for the next patient. Outcome measures included timely patient discharge and intern work hours.

Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.

Inflammation is a growing area of research in neurodegeneration. In Huntington's disease (HD), a fatal inherited neurodegenerative disease caused by a CAG-repeat expansion in the gene encoding huntingtin, patients have increased plasma levels of inflammatory cytokines and circulating monocytes that are hyper-responsive to immune stimuli. Several mouse models of HD also show elevated plasma levels of inflammatory cytokines.

Dysfunction of the CNS-heart axis in mouse models of Huntington's disease.

Cardiac remodelling and contractile dysfunction occur during both acute and chronic disease processes including the accumulation of insoluble aggregates of misfolded amyloid proteins that are typical features of Alzheimer's, Parkinson's and Huntington's disease (HD). While HD has been described mainly as a neurological disease, multiple epidemiological studies have shown that HD patients exhibit a high incidence of cardiovascular events leading to heart failure, and that this is the second highest cause of death. Given that huntingtin is ubiquitously expressed, cardiomyocytes may be at risk of an HD-related dysfunction.

Workplace model for physical therapists and occupational therapists.

Purpose: The purpose of this paper is to test a model linking physical therapy (PT) and occupational therapy (OT) practitioners' perceptions of resonant leadership, structural empowerment and psychological empowerment to their experiences of spirit at work (SAW), job satisfaction and organizational commitment within the Canadian workplace.

Design/methodology/approach: The authors tested the model using LISREL 8.80 and survey data from 101 OTs and 169 PTs, randomly selected by the Alberta professional licensing associations.

Resonant leadership, workplace empowerment, and "spirit at work": impact on RN job satisfaction and organizational commitment.

Canadian researchers have developed the Spirit At Work (SAW) tool for identifying the experiences of individuals who are passionate about and energized by their work. This article describes (a) what registered nurses perceive as contributing to their personal SAW; and (b) the relationships among resonant leadership, structural empowerment concepts, psychological empowerment concepts, SAW concepts, job satisfaction, organizational commitment, and the demographic variables of experience, education, and rank in the RN workplace. The theoretical model was tested using LISREL 8.

HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration.

Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine-rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntington's disease (HD), a protein-folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion in the huntingtin protein. We found that HDAC4 associates with huntingtin in a polyglutamine-length-dependent manner and co-localises with cytoplasmic inclusions.

Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies.

Neurodegenerative disorders such as Huntington's disease are hallmarked by neuronal intracellular inclusion body formation. Whether proteasomes are irreversibly recruited into inclusion bodies in these protein misfolding disorders is a controversial subject. In addition, it has been proposed that the proteasomes may become clogged by the aggregated protein fragments, leading to impairment of the ubiquitin-proteasome system.

Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease.

Huntington disease (HD) is a devastating, late-onset, inherited neurodegenerative disorder that manifests with personality changes, movement disorders, and cognitive decline. It is caused by a CAG repeat expansion in exon 1 of the HTT gene that translates to a polyglutamine tract in the huntingtin protein (HTT). The formation of HTT fragments has been implicated as an essential step in the molecular pathogenesis of HD and several proteases that cleave HTT have been identified.

Oral administration of the pimelic diphenylamide HDAC inhibitor HDACi 4b is unsuitable for chronic inhibition of HDAC activity in the CNS in vivo.

Histone deacetylase (HDAC) inhibitors have received considerable attention as potential therapeutics for a variety of cancers and neurological disorders. Recent publications on a class of pimelic diphenylamide HDAC inhibitors have highlighted their promise in the treatment of the neurodegenerative diseases Friedreich's ataxia and Huntington's disease, based on efficacy in cell and mouse models. These studies' authors have proposed that the unique action of these compounds compared to hydroxamic acid-based HDAC inhibitors results from their unusual slow-on/slow-off kinetics of binding, preferentially to HDAC3, resulting in a distinctive pharmacological profile and reduced toxicity.

Rhodium-catalyzed [2 + 2] cycloaddition of ynamides with nitroalkenes.

In the presence of a diene-ligated rhodium complex, ynamides and nitroalkenes undergo catalytic [2 + 2] cycloadditions to provide cyclobutenamides. The presence of sodium tetraphenylborate was found to be crucial for the reactions to proceed efficiently.

SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive neurological disorder for which there are no disease-modifying treatments. Transcriptional dysregulation is a major molecular feature of HD, which significantly contributes to disease progression. Therefore, the development of histone deacetylase (HDAC) inhibitors as therapeutics for HD has been energetically pursued.

Palladium-catalyzed hydroacyloxylation of ynamides.

In the presence of substoichiometric Pd(OAc)(2), carboxylic acids undergo highly regio- and stereoselective additions to ynamides to provide α-acyloxyenamides.

The relationship between structural empowerment and psychological empowerment for nurses: a systematic review.

Aim: To describe the findings of a systematic review examining the relationship between structural empowerment and psychological empowerment for registered nurses (RNs).

Background: Workplace empowerment research reveals a link between empowerment and positive work behaviours and attitudes. Research demonstrating the essential relationship between structural empowerment and psychological empowerment will provide direction for future interventions aimed at the development of a strong and effective health care sector.

SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis.

Huntington's disease (HD), an incurable neurodegenerative disorder, has a complex pathogenesis including protein aggregation and the dysregulation of neuronal transcription and metabolism. Here, we demonstrate that inhibition of sirtuin 2 (SIRT2) achieves neuroprotection in cellular and invertebrate models of HD. Genetic or pharmacologic inhibition of SIRT2 in a striatal neuron model of HD resulted in gene expression changes including significant down-regulation of RNAs responsible for sterol biosynthesis.

Reversal of long-term dendritic spine alterations in Alzheimer disease models.

Synapse loss is strongly correlated with cognitive impairment in Alzheimer's disease (AD). We have previously reported the loss of dendritic spines and the presence of dystrophic neurites in both the hippocampi of transgenic mice overexpressing amyloid precursor protein (APP) and in the human brain affected with AD. In the studies reported here we have asked whether the acute alterations in dendritic spines induced by Abeta, as well as the chronic loss of spine density seen in hAPP transgenic mice, are reversible by treatments that restore the cAMP/PKA/CREB signaling pathway or proteasome function to control levels.