Negative Regulation of Hepatitis C Virus Specific Immunity Is Highly Heterogeneous and Modulated by Pegylated Interferon-Alpha/Ribavirin Therapy

Specific inhibitory mechanisms suppress the T-cell response against the hepatitis C virus (HCV) in chronically infected patients. However, the relative importance of suppression by IL-10, TGF-β and regulatory T-cells and the impact of pegylated interferon-alpha and ribavirin (PegIFN-α/ribavirin) therapy on these inhibitory mechanisms are still unclear. We revealed that coregulation of the HCV-specific T-cell responses in blood of 43 chronic HCV patients showed a highly heterogeneous pattern before, during and after PegIFN-α/ribavirin. Prior to treatment, IL-10 mediated suppression of HCV-specific IFN-γ production in therapy-naive chronic HCV patients was associated with higher HCV-RNA loads, which suggests that protective antiviral immunity is controlled by IL-10. In addition, as a consequence of PegIFN-α/ribavirin therapy, negative regulation of especially HCV-specific IFN-γ production by TGF-β and IL-10 changed dramatically. Our findings emphasize the importance of negative regulation for the dysfunctional HCV-specific immunity, which should be considered in the design of future immunomodulatory therapies

Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease

To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments.We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models.By year 3, cognitive impairment was diagnosed in 15-38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer's disease Aβ amyloid pathology (lower CSF Aβ 1-42); and (4) genes (COMT val/val and BDNF val/val genotypes).Cognitive impairment in PD increases in frequency 50-200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease plaque pathology, and genetic factors

Surgical site infection rates in 16 cities in Turkey: findings of the International Nosocomial Infection Control Consortium (INICC)

Conclusions: In most of the 22 types of SP analyzed, our SSI rates were higher than the CDC NHSN rates and similar to the INICC rates. This study advances the knowledge of SSI epidemiology in Turkey, allowing the implementation of targeted interventions. Copyright (C) 2015 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Surgical site infection rates in 16 cities in Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Surgical site infections (SSIs) are a threat to patient safety; however, there were no available data on SSI rates stratified by surgical procedure (SP) in Turkey. METHODS: Between January 2005 and December 2011, a cohort prospective surveillance study on SSIs was conducted by the International Nosocomial Infection Control Consortium (INICC) in 20 hospitals in 16 Turkish cities. Data from hospitalized patients were registered using the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) methods and definitions for SSIs. Surgical procedures (SPs) were classified into 22 types according to International Classification of Diseases, Ninth Revision criteria. RESULTS: We recorded 1879 SSIs, associated with 41,563 SPs (4.3%; 95% confidence interval, 4.3-4.7). Among the results, the SSI rate per type of SP compared with rates reported by the INICC and CDC NHSN were 11.9% for ventricular shunt (vs 12.9% vs 5.6%); 5.3% for craniotomy (vs 4.4% vs 2.6%); 4.9% for coronary bypass with chest and donor incision (vs 4.5 vs 2.9); 3.5% for hip prosthesis (vs 2.6% vs 1.3%), and 3.0% for cesarean section (vs 0.7% vs 1.8%). CONCLUSIONS: In most of the 22 types of SP analyzed, our SSI rates were higher than the CDC NHSN rates and similar to the INICC rates. This study advances the knowledge of SSI epidemiology in Turkey, allowing the implementation of targeted interventions

Baseline biomarker predictors of investigator diagnosis of cognitive impairment.

<p>Baseline biomarker predictors of investigator diagnosis of cognitive impairment.</p

Biomarker availability at baseline and longitudinally.

<p>Biomarker availability at baseline and longitudinally.</p

Baseline demographic and clinical characteristics.

<p>Baseline demographic and clinical characteristics.</p