One-year swallowing outcomes following transoral laser microsurgery +/- adjuvant therapy versus primary chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma.

Objectives: To assess the between-group change in swallowing function from baseline to 12 months following treatment, for patients treated for resectable stage III and IVA oropharyngeal squamous cell carcinoma. To assess the within-group change in swallowing function between 3 and 12 months following treatment.

Design: Non-randomised cohort study.

Taking Personalized Medicine Seriously: Biomarker Approaches in Phase IIb/III Studies in Major Depression and Schizophrenia.

The success rate in the development of psychopharmacological compounds is insufficient. Two main reasons for failure have been frequently identified: 1) treating the wrong patients and 2) using the wrong dose. This is potentially based on the known heterogeneity among patients, both on a syndromal and a biological level.

Is blood pressure control for stroke prevention the correct goal? The lost opportunity of preventing hypertension.

Background And Purpose: Although pharmacological treatment of hypertension has important health benefits, it does not capture the benefit of maintenance of ideal health through the prevention or delay of hypertension.

Methods: A total of 26 875 black and white participants aged 45+ years were assessed and followed for incident stroke events. The association was assessed between incident stroke and: (1) systolic blood pressure (SBP)categorized as normal (<120 mm Hg), prehypertension (120-139 mm Hg), stage 1 hypertension (140-159 mm Hg), and stage 2 hypertension (160 mm Hg+), and (2) number of classes of antihypertensive medications, classified as none, 1, 2, or 3 or more.

Accumulation of metabolic cardiovascular risk factors in black and white young adults over 20 years.

Background: Cross-sectional clustering of metabolic risk factors for cardiovascular disease in middle-aged adults is well described, but less is known regarding the order in which risk factors develop through young adulthood and their relation to subclinical atherosclerosis.

Method And Results: A total of 3178 black and white women and men in the Coronary Artery Risk Development in Young Adults study were assessed to identify the order in which cardiovascular disease risk factors including diabetes, hypertension, dyslipidemia (low high-density lipoprotein cholesterol or high triglyceride levels), hypercholesterolemia (high total or low-density lipoprotein cholesterol), and obesity develop. Observed patterns of risk factor development were compared with those expected if risk factors accumulated randomly, given their overall distribution in the population.

GLI2 inhibition abrogates human leukemia stem cell dormancy.

Background: Dormant leukemia stem cells (LSC) promote therapeutic resistance and leukemic progression as a result of unbridled activation of stem cell gene expression programs. Thus, we hypothesized that 1) deregulation of the hedgehog (Hh) stem cell self-renewal and cell cycle regulatory pathway would promote dormant human LSC generation and 2) that PF-04449913, a clinical antagonist of the GLI2 transcriptional activator, smoothened (SMO), would enhance dormant human LSC eradication.

Methods: To test these postulates, whole transcriptome RNA sequencing (RNA-seq), microarray, qRT-PCR, stromal co-culture, confocal fluorescence microscopic, nanoproteomic, serial transplantation and cell cycle analyses were performed on FACS purified normal, chronic phase (CP) chronic myeloid leukemia (CML), blast crisis (BC) phase CML progenitors with or without PF-04449913 treatment.

Neural correlates of the preserved inhibition of return in schizophrenia.

Inhibition of return (IOR) is an attentional mechanism that previously has been reported to be either intact or blunted in subjects with schizophrenia (SCZ). In the present study, we explored the neural mechanism of IOR in SCZ by comparing the target-locked N1 and P1 activity evoked by valid-cued trials with that evoked by invalid-cued trials. Twenty-seven schizophrenia patients and nineteen healthy controls participated in a task involving covert orienting of attention with two stimulus onset asynchronies (SOAs: 700 ms and 1200 ms) during which 64-channel EEG data were recorded.

A Phase II study of a histamine H₃ receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy.

This Phase II exploratory study assessed GSK239512, a brain penetrant histamine H₃ receptor antagonist, versus placebo on cognitive impairment in 50 stable outpatients with schizophrenia. Subjects were randomized to placebo or GSK239512 for 7 weeks (4 weeks titration). GSK239512 was associated with a small positive effect size (ES) on the CogState Schizophrenia Battery (CSSB) Composite Score (ES=0.

Drug development in schizophrenia: are glutamatergic targets still worth aiming at?

Purpose Of Review: The ketamine model has dominated drug discovery in schizophrenia over the past decade, supported by genetic and postmortem evidence implicating glutamatergic transmission. This review assesses recent successes and disappointments of glutamatergic agents and identifies promising new directions.

Recent Findings: Strategies focused on enhancing activity of the N-methyl D-aspartate (NMDA) receptor via direct agonists at the glycine site or by inhibition of glycine reuptake have produced modest and often inconsistent evidence of efficacy, as have approaches to reduce excessive glutamate release by lamotrigine or by mGluR2/3 agonists.

Review of Twitter for infectious diseases clinicians: useful or a waste of time?

Twitter is a social networking service that has emerged as a valuable tool for healthcare professionals (HCPs). It is the only platform that allows one to connect, engage, learn, and educate oneself and others in real time on a global scale. HCPs are using social media tools to communicate, educate, and engage with their peers worldwide.

Lipoprotein particles and incident type 2 diabetes in the multi-ethnic study of atherosclerosis.

Objective: In the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated associations of baseline levels of a lipoprotein-based insulin resistance (IR) index (LP-IR), IR-related lipoprotein particles, mean particle sizes, and lipids, with incident type 2 diabetes, independent of confounders, glucose, insulin, and HOMA-IR.

Research Design And Methods: Among 5,314 adults aged 45-84 years without baseline diabetes or cardiovascular disease, 656 cases of diabetes were identified during a mean follow-up of 7.7 years.

The impact of NMDA receptor hypofunction on GABAergic neurons in the pathophysiology of schizophrenia.

While the dopamine hypothesis has dominated schizophrenia research for several decades, more recent studies have highlighted the role of fast synaptic transmitters and their receptors in schizophrenia etiology. Here we review evidence that schizophrenia is associated with a reduction in N-methyl-d-aspartate receptor (NMDAR) function. By highlighting postmortem, neuroimaging and electrophysiological studies, we provide evidence for preferential disruption of GABAergic circuits in the context of NMDAR hypo-activity states.

Atrial fibrillation incidence and risk factors in relation to race-ethnicity and the population attributable fraction of atrial fibrillation risk factors: the Multi-Ethnic Study of Atherosclerosis.

Purpose: We studied incident atrial fibrillation (AF) in the prospective community-based Multi-Ethnic Study of Atherosclerosis (MESA). Reportedly, non-Hispanic blacks (NHBs) have a lower AF burden compared with their non-Hispanic white (NHW) counterparts. Information on the epidemiology of AF in Hispanic and Asian populations is much more limited.

Dietary intake relative to cardiovascular disease risk factors in individuals with chronic spinal cord injury: a pilot study.

Background: The relationship between cardiovascular disease (CVD) risk factors and dietary intake is unknown among individuals with spinal cord injury (SCI).

Objective: To investigate the relationship between consumption of selected food groups (dairy, whole grains, fruits, vegetables, and meat) and CVD risk factors in individuals with chronic SCI.

Methods: A cross-sectional substudy of individuals with SCI to assess CVD risk factors and dietary intake in comparison with age-, gender-, and race-matched able-bodied individuals enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

ACC/AHA/AACVPR/AAFP/ANA concepts for clinician-patient shared accountability in performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures.

Developed in collaboration with the National Committee for Quality Assurance, the American Society of Health-System Pharmacists, and the American Medical Association–Physician Consortium for Performance Improvement Endorsed by the American Society of Health-System Pharmacists

Mechanisms of heart failure in obesity.

Heart failure is a leading cause of morbidity and mortality and its prevalence continues to rise. Because obesity has been linked with heart failure, the increasing prevalence of obesity may presage further rise in heart failure in the future. Obesity-related factors are estimated to cause 11% of heart failure cases in men and 14% in women.

Bad bugs need old drugs: a stewardship program's evaluation of minocycline for multidrug-resistant Acinetobacter baumannii infections.

Background: Minocycline is an "old-drug" with Food and Drug Administration approval for the treatment of infection due to Acinetobacter species. The purpose of this study is to describe an Antimicrobial Stewardship Program's evaluation of minocycline for the treatment of patients with multidrug resistant A. baumannii (MDR-AB) infections.

Effects of weight regain following intentional weight loss on glucoregulatory function in overweight and obese adults with pre-diabetes.

Objective: To assess the extent to which initial, intentional weight loss-associated improvements in glucose tolerance and insulin action are diminished with weight regain.

Methods: 138 overweight and obese (BMI: 32.4±3.

Effects of a community-based weight loss intervention on adipose tissue circulating factors.

Aims: Obesity is associated with metabolic dysfunctions, which may be mediated by changes in adipose tissue signaling factors. These molecules are denoted as Adipose Tissue Generated Mediators of CardioVascular Risk (ATGMCVR) here, and include leptin, adiponectin, C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and plasminogen activator inhibitor 1 (PAI-1). This study examined the effect of a weight loss program on ATGMCVR in obese adults with prediabetes.

Association of menopause age and N-terminal pro brain natriuretic peptide: the Multi-Ethnic Study of Atherosclerosis.

Objective: Menopause age can affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before age 45 y) and menopause age with N-terminal pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure.

Methods: Our cross-sectional study included 2,275 postmenopausal women, aged 45 to 85 years and without clinical CVD (2000-2002), from the Multi-Ethnic Study of Atherosclerosis.

Review of rapid diagnostic tests used by antimicrobial stewardship programs.

Rapid microbiologic tests provide opportunities for antimicrobial stewardship programs to improve antimicrobial use and clinical and economic outcomes. Standard techniques for identification of organisms require at least 48-72 hours for final results, compared with rapid diagnostic tests that provide final organism identification within hours of growth. Importantly, rapid microbiologic tests are considered "game changers" and represent a significant advancement in the management of infectious diseases.