Identification of p38 MAPK as a novel therapeutic target for Friedreich's ataxia.

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative disorder caused by decreased expression of frataxin, a protein that localizes to mitochondria and is critical for iron-sulfur-cluster (ISC) assembly. There are no proven effective treatments for FRDA. We previously screened a random shRNA library and identified a synthetic shRNA (gFA11) that reverses the growth defect of FRDA cells in culture.

Cardiac Resynchronization Therapy in Patients With Heart Failure and Narrow QRS Complexes.

Background: Cross correlation analysis (CCA) using tissue Doppler imaging has been shown to be associated with outcome after cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with wide QRS. However, its significance in patients with narrow QRS treated with CRT is unknown.

Objectives: The aim of the current study was to investigate the association of mechanical activation delay by CCA with study outcome in patients with HF enrolled in the EchoCRT trial.

Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection.

Approximately three quarters of acute hepatitis C (HCV) infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using ImmunoChip in European and African ancestries.

Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression.

The Incidence and Prevalence of Systemic Lupus Erythematosus in New York County (Manhattan), New York: The Manhattan Lupus Surveillance Program.

Objective: The Manhattan Lupus Surveillance Program (MLSP) is a population-based registry designed to determine the prevalence of systemic lupus erythematosus (SLE) in 2007 and the incidence from 2007 to 2009 among residents of New York County (Manhattan), New York, and to characterize cases by race/ethnicity, including Asians and Hispanics, for whom data are lacking.

Methods: We identified possible SLE cases from hospital records, rheumatologist records, and administrative databases. Cases were defined according to the American College of Rheumatology (ACR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, or the treating rheumatologist's diagnosis.

Cutaneous microvascular perfusion responses to insulin iontophoresis are differentially affected by insulin resistance after spinal cord injury.

What is the central question of this study? What impact does insulin resistance have on cutaneous perfusion responses to insulin iontophoresis in vascular beds with markedly reduced or functionally ablated sympathetic nervous system vasomotor function resulting from spinal cord injury? What is the main finding and its importance? Persons with spinal cord injury have sublesional microvascular endothelial dysfunction, as indicated by a blunted cutaneous perfusion response to acetylcholine iontophoresis, and the presence of insulin resistance has a further confounding effect on endothelium-mediated changes to cutaneous perfusion in the lower extremities. Endothelium-mediated mechanisms that regulate skin blood flow might play an integral role in optimizing skin perfusion in vascular beds with sympathetic nervous system vasomotor impairment, such as in spinal cord injury (SCI). Insulin is a vasoactive hormone and second messenger of nitric oxide that facilitates endothelium-mediated dilatation.

Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010.

Importance: Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making.

Objectives: To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk.

Postapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review.

 To characterize the prospective controlled clinical studies for all novel drugs that were initially approved by the Food and Drug Administration on the basis of limited evidence. Systematic review. Drugs@FDA database and PubMed.

Prognostic implications of left ventricular global longitudinal strain in heart failure patients with narrow QRS complex treated with cardiac resynchronization therapy: a subanalysis of the randomized EchoCRT trial.

Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic function and correlates inversely with the extent of LV myocardial scar and fibrosis. The present subanalysis of the Echocardiography Guided CRT trial investigated the prognostic value of LV GLS in patients with narrow QRS complex.

Methods And Results: Left ventricular (LV) global longitudinal strain (GLS) was measured on the apical 2-, 4- and 3-chamber views using speckle tracking analysis.

Breast Tissue Expanders with Magnetic Ports: Clinical Experience at 1.5 T.

Background: The purpose of this study was to evaluate breast tissue expanders with magnetic ports for safety in patients undergoing abdominal/pelvic magnetic resonance angiography before autologous breast reconstruction.

Methods: Magnetic resonance angiography of the abdomen and pelvis at 1.5 T was performed in 71 patients in prone position with tissue expanders with magnetic ports labeled "MR Unsafe" from July of 2012 to May of 2014.

Effect of cardiac resynchronization therapy in patients with diabetes randomized in EchoCRT.

Aims: As patients with heart failure (HF) and concomitant diabetes carry a poor prognosis, this post-hoc subgroup analysis aimed to compare the outcomes of patients with and without diabetes randomized in the Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) study.

Methods And Results: EchoCRT randomized patients with a QRS duration <130 ms and echocardiographic evidence of left ventricular dyssynchrony to CRT turned on (CRT=ON) vs. off (CRT=OFF) following device implantation.

Rheumatology Research Foundation Clinician Scholar Educator Award: Fifteen Years Promoting Rheumatology Educators and Education.

Objective: The Rheumatology Research Foundation's Clinician Scholar Educator (CSE) award is a 3-year career development award supporting medical education research while providing opportunities for mentorship and collaboration. Our objective was to document the individual and institutional impact of the award since its inception, as well as its promise to strengthen the subspecialty of rheumatology.

Methods: All 60 CSE Award recipients were surveyed periodically.

Association of persistent or worsened echocardiographic dyssynchrony with unfavourable clinical outcomes in heart failure patients with narrow QRS width: a subgroup analysis of the EchoCRT trial.

Aims: EchoCRT was a randomized trial of cardiac resynchronization therapy (CRT) in severely symptomatic heart failure (HF) patients with narrow QRS width <130 ms, ejection fraction ≤35%, and echocardiographic dyssynchrony. All received CRT implants which were then randomized to CRT-On or CRT-Off. While the trial showed no benefit of CRT to these patients, the aim of this subgroup analysis was to test the hypothesis that persistent or worsening dyssynchrony is associated with unfavourable clinical outcomes.

The effect of QRS duration on cardiac resynchronization therapy in patients with a narrow QRS complex: a subgroup analysis of the EchoCRT trial.

Aims: In EchoCRT, a randomized trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome occurred more frequently in the CRT when compared with the control group. According to current heart failure guidelines, CRT is recommended in patients with a QRS duration of ≥120 ms. However, there is some ambiguity from clinical trial data regarding the benefit of patients with a QRS duration of 120-130 ms.

Community practice patterns for bacterial corneal ulcer evaluation and treatment.

Objective: To examine current practice patterns in the management of bacterial keratitis among U.S. ophthalmologists and differences in the management and opinions between cornea specialists and non-cornea specialists.

Oral clefting in china over the last decade: 205,679 patients.

Background: China is the most populated country and has one of the highest prevalences of oral clefting. The present study reports the epidemiology and surgical procedures performed on the largest reported cohort of individuals with clefting in China.

Methods: A retrospective review of patients who received cleft repair through Smile Train in China from 2000 to 2011 was conducted.

Cleft lip and/or palate: one organization's experience with more than a quarter million surgeries during the past decade.

Background: A charitable surgical relief organization (Smile Train) enables local physicians in developing countries to provide surgical treatment of cleft lip and/or palate. The following study reviews the epidemiological data from more than 260,000 surgeries performed in India through this organization from 2000 until January 1, 2012.

Methods: Demographic and clinical patient data were collected from the participating surgeons, recorded in Excel (Microsoft, Redmond, WA), and analyzed using Software Package for the Social Sciences (IBM, Armonk, NY).

A neurobiological hypothesis of treatment-resistant depression - mechanisms for selective serotonin reuptake inhibitor non-efficacy.

First-line treatment of major depression includes administration of a selective serotonin reuptake inhibitor (SSRI), yet studies suggest that remission rates following two trials of an SSRI are <50%. The authors examine the putative biological substrates underlying "treatment resistant depression (TRD)" with the goal of elucidating novel rationales to treat TRD. We look at relevant articles from the preclinical and clinical literature combined with clinical exposure to TRD patients.

Direct-to-consumer Internet promotion of robotic prostatectomy exhibits varying quality of information.

Robotic surgery to remove a cancerous prostate has become a popular treatment. Internet marketing of this surgery provides an intriguing case study of direct-to-consumer promotions of medical devices, which are more loosely regulated than pharmaceutical promotions. We investigated whether the claims made in online promotions of robotic prostatectomy were consistent with evidence from comparative effectiveness studies.

Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection.

Background & Aims: Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms.

Methods: Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT, and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during 10 acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of overall changes.

Telmisartan in high-risk cardiovascular patients.

Increasing attention is being devoted to the use of combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in order to achieve maximal blockade of the renin-angiotensin system (RAS) in patients at high risk of cardiovascular events. This approach has been adopted in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), which compared the effects of the ARB telmisartan and the ACE inhibitor ramipril, alone and in combination, on cardiovascular mortality and morbidity in high-risk patients with vascular disease or diabetes mellitus and end-organ damage. The results showed that telmisartan was as effective as ramipril for the primary cardiovascular outcome during a 56-month follow-up but was better tolerated.