Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation.

Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex.

Quantifying cerebrovascular reactivity in anterior and posterior cerebral circulations during voluntary breath holding.

What is the central question of this study? We developed and validated a 'stimulus index' (SI; ratio of end-tidal partial pressures of CO and O ) method to quantify cerebrovascular reactivity (CVR) in anterior and posterior cerebral circulations during breath holding. We aimed to determine whether the magnitude of CVR is correlated with breath-hold duration. What is the main finding and its importance? Using the SI method and transcranial Doppler ultrasound, we found that the magnitude of CVR of the anterior and posterior cerebral circulations is not positively correlated with physiological or psychological break-point during end-inspiratory breath holding.

Retinal vascular occlusion: a window to diagnosis of familial and acquired thrombophilia and hypofibrinolysis, with important ramifications for pregnancy outcomes.

Aim: Our specific aim was to document the pathoetiologic importance of thrombophilia among females presenting with severe ischemic retinal vein (RVO) or retinal artery (RAO) occlusion, without typical risk factors, and to emphasize that the ophthalmologists' diagnosis of thrombophilia has important diagnostic and therapeutic downstream ramifications for nonocular thrombosis, including reproductive outcomes.

Methods: We evaluated familial and acquired thrombophilia in 60 females with RVO (central RVO, n=52; branch RVO, n=8) and 16 with RAO (central RAO, n=11; branch RAO, n=5). They were referred by retinologists, without typical risk factors for RVO/RAO and/or severe ocular ischemic presentation.

Percutaneous Epicardial Pacing using a Novel Insulated Multi-electrode Lead.

Introduction: Epicardial cardiac resynchronization therapy (CRT) permits unrestricted electrode positioning. However, this requires surgical placement of device leads and the risk of unwanted phrenic nerve stimulation. We hypothesized that shielded electrodes can capture myocardium without extracardiac stimulation.

Stability-based assessment of Monteggia-type injuries predicts failure of treatment.

Paediatric Monteggia-type injuries are complicated by treatment failure and posterior interosseous nerve palsy, without reliable predictive indicators. Outcome is considered to be good, with little patient-reported evidence. We propose novel radiographic parameters.

Novel Techniques in Epilepsy Management: Venous Pacing and Capture of Electrical Activity in the Primate Cortex.

Objective: Pharmacotherapy for epilepsy is limited with 30% of patients refractory to this approach of suppressing seizures. Current surgical options are invasive and carry significant morbidities including infection, bleeding, and the potential for deleterious neurocognitive effects. As a result, there is a burgeoning need for innovation to develop safer and efficacious interventions.

Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease.

Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to quantify GDF11, resolved from its homolog, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging.

Reversing diet-induced metabolic dysregulation by diet switching leads to altered hepatic de novo lipogenesis and glycerolipid synthesis.

In humans, low-energy diets rapidly reduce hepatic fat and improve/normalise glycemic control. Due to difficulties in obtaining human liver, little is known about changes to the lipid species and pathway fluxes that occur under these conditions. Using a combination of stable isotope, and targeted metabolomic approaches we investigated the acute (7-9 days) hepatic effects of switching high-fat high-sucrose diet (HFD) fed obese mice back to a chow diet.

The lognormal age of onset distribution in Perthes' disease: an analysis from a large well-defined cohort.

Aims: To explore the of age of onset distribution for Perthes' disease of the hip, with particular reference to gender, laterality and conformity to the lognormal distribution.

Patients And Methods: A total of 1082 patients were identified from the Liverpool Perthes' Disease Register between 1976 and 2010, of which 992 had the date of diagnosis recorded. In total, 682 patients came from the geographical area exclusively served by Alder Hey Hospital, of which 673 had a date of diagnosis.

Increasing nursing students' understanding and accuracy with medical dose calculations: A collaborative approach.

Background: Accurate calculation of medication dosages can be challenging for nursing students. Specific interventions related to types of errors made by nursing students may improve the learning of this important skill.

Objective: The objective of this study was to determine areas of challenge for students in performing medication dosage calculations in order to design interventions to improve this skill.

Treatment of complex idiopathic clubfoot using the modified Ponseti method: up to 11 years follow-up.

Unlabelled: Complex idiopathic clubfeet are distinguished by significant shortening, rigid equinus with a deep crease above the heel, severe plantar flexion of all metatarsals, a deep plantar crease seven across the full width of the sole of the foot and high cavus with a short and hyperextended big toe. Ponseti has devised a modified technique for treating complex clubfeet. We retrospectively identified 11 children (nine males and two females) with 17 complex clubfeet who were treated with the modified Ponseti method.

Echocardiographic and Fluoroscopic Fusion Imaging for Procedural Guidance: An Overview and Early Clinical Experience.

There has been significant growth in the volume and complexity of percutaneous structural heart procedures in the past decade. Increasing procedural complexity and accompanying reliance on multimodality imaging have fueled the development of fusion imaging to facilitate procedural guidance. The first clinically available system capable of echocardiographic and fluoroscopic fusion for real-time guidance of structural heart procedures was approved by the US Food and Drug Administration in 2012.

Development and validation of a patient-centered knowledge scale for left ventricular assist device placement.

Background: A central tenet of patient-centered health care advocated by the Institute of Medicine and the American Medical Association is to enhance informed decision-making in a way that incorporates patient values, knowledge and beliefs. Achievement of this goal is constrained by a lack of validated measures of patients' knowledge needs.

Methods: In this study we present a comprehensive and valid methodology for developing a clinically informed and patient-centered measure of knowledge about left ventricular assist device (LVAD) therapy to facilitate discussion and measure candidate understanding of treatment options.

PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications.

Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro.

Extinction efficiencies for metallic fibers in the infrared: erratum.

In this erratum, a correction of a previously computed extinction spectrum of a sample of silver fibers in the infrared [Appl. Opt.48, 5095 (2009)APOPAI0003-693510.

A Qualitative Exploration of a Clinical Ethicist's Role and Contributions During Family Meetings.

Despite the interpersonal nature of family meetings and the frequency in which they occur, the clinical ethics literature is devoid of any rich descriptions of what clinical ethicists should actually be doing during family meetings. Here, we propose a framework for describing and understanding "transitioning" facilitation skills based on a retrospective review of our internal documentation of 100 consecutive cases (June 01, 2013-December 31, 2014) wherein a clinical ethicist facilitated at least one family meeting. The internal documents were analyzed using qualitative methodologies, i.

Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy.

Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes of non-degenerative muscle wasting.

Comparing and characterizing transient and steady-state tests of the peripheral chemoreflex in humans.

What is the central question of this study? We aimed to characterize the cardiorespiratory and cerebrovascular responses to transient and steady-state tests of the peripheral chemoreflex and to compare the hypoxic ventilatory responses (HVRs) between these tests. What is the main finding and its importance? The cardiovascular and cerebrovascular responses to transient tests were small in magnitude and short in duration. The steady-state isocapnic hypoxia test elicited a larger HVR than the transient 100% N(2) test, but the response magnitudes were correlated within individuals.

Profile of a Malignant Brain Tumour in Jamaica: An Eight-year Review, 2005 to 2012.

Objective: Glioblastoma multiforme (GBM) is the most malignant and most common primary brain tumour worldwide. This study was undertaken to investigate the demographics of this tumour in Jamaica as there is to date no such published data. Data from the recently started Intracranial Tumour Registry (ITR) at the University Hospital of the West Indies was used.

Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism.

Liver steatosis is associated with the development of insulin resistance and the pathogenesis of type 2 diabetes. We tested the hypothesis that protein signals originating from steatotic hepatocytes communicate with other cells to modulate metabolic phenotypes. We show that the secreted factors from steatotic hepatocytes induce pro-inflammatory signaling and insulin resistance in cultured cells.