Dot plot and histograms representing TLR4 and TLR2 levels in monocytes.

<p>(A1-A3) Monocytes/lymphocyte cell population after CD14-positive cell staining. (B-C) Shift to the right demonstrating an increase in the amount of TLR4 staining in the monocytes. Specific mean fluorescence (MFI) can be quantified from these histograms for each case. (D) TLR4 levels on the population of monocytes as measured using relative mean fluorescence intensity (rMFI). (C) ‘reduced EF‘ patients (EF<45%) and ‘preserved EF‘ patients (EF>55%). (E) TLR2 levels on the population of monocytes as measured using rMFI. FACS analysis,* P<0.03 patient with ‘reduced EF’ TLR4 was higher than that of patients with ‘preserved EF’.</p

Biomarkers in the plasma and white blood cells count.

<p>Protein expression of different stress biomarkers in patients before CABG surgery: ‘reduced EF’ and ‘preserved EF’ patients. (A) CRP, p = 0.038, (B) NT Pro-BNP, *P<0.0001, (C) LDH, p = 0.497 reduced versus ‘preserved EF’, (D) WBC/Monocyte/Neutrophils count of the 2 groups, no statistical difference was observed.</p

Baseline characteristics of the study population (A) and medication (B).

<p>Baseline characteristics of the study population (A) and medication (B).</p

Gene expression of biomarkers of injury and immunostaining of TLR4 in patient auricles.

<p>(A-D) TLR4 and NOX4 are activated resulting in elevated TNF-α in the auricles. Auricles obtained during CABG surgery presented higher expression of TLR4 (P<0.03), BNP (P<0.05), NOX4 (P<0.03), and TNF-α (P = 0.135) in reduced versus ‘preserved EF’. (E) TLR2 expression was similar in both groups. (F1-F2) Representative photographs show double-immunostaining of Troponin I and TLR4 in ‘preserved EF’ auricle. (F3-F4) Representative photographs show double-immunostaining of troponin I and TLR4 in the ‘reduced EF’ auricle. TLR4 staining revealed an apparent upregulation in all ‘reduced EF’ patients examined compared to ‘preserved EF’ patients' tissue.</p

Comparison of a 12-month post-surgical follow up to the baseline data.

<p>Legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120175#pone.0120175.t002" target="_blank">Table 2</a>:</p><p>*P = 0.03 vs baseline</p><p>Comparison of a 12-month post-surgical follow up to the baseline data.</p

miR expression.

<p>A. miR320a expression in the serum of patients undergoing CABG surgery, with reduced EF was higher than preserved EF, * P <0.001. B. The miR15a, is presented in Fig B and noted as unchanged.</p

Epilepsy in Rett syndrome-Lessons from the Rett networked database

Objective Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype–phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming. Methods Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS Version 21 software, logistic regression, and Kaplan-Meier survival curves. Results Epilepsy was present in 68.1% of the patients, with uncontrolled seizures in 32.6% of the patients with epilepsy. Mean age of onset of epilepsy was 4.68 ± (standard deviation) 3.5 years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r = 0.668, p < 0.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p.R133C mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [OR] 2.46, confidence interval [CI] 95% 1.3–4.66), but not for severe epilepsy. The p.R255X mutation conferred an increased risk for epilepsy (OR 2.07, CI 95% 1.2–3.59) as well as for severe epilepsy (OR 3.4, CI 95% 1.6–7.3). The p.T158M and p.C306C mutations relatively increased the risk for severe epilepsy (OR 3.09 and 2.69, CI 95% 1.48–6.4 and 1.19–6.05, respectively), but not for epilepsy occurrence. Significance Various mutations in the MECP2 gene have a different influence on epilepsy, unrelated to the severity of the general Rett phenotype. This might suggest a site-specific effect of MeCp2 on epileptic pathways. Further investigation of these mechanisms should promote better understanding of epileptogenesis in Rett syndrome

Therapeutic response to peg-IFN-alpha-2b and ribavirin in HIV/HCV co-infected African-American and Caucasian patients as a function of HCV viral kinetics and interferon pharmacodynamics

In this study we sought to characterize the relationship between several pharmacokinetic (PK) and pharmacodynamic (PD) parameters and virologic responses among HIV/HCV genotype-1 co-infected patients receiving pegylated interferon-alpha-2b (peg-IFN2b) and ribavirin. We also tried to establish the underlying mechanisms that lead to poor SVR rates observed with African Americans (AA) against Caucasians and compared their results with those observed in a cohort of HCV mono-infected patients. Among our studied population, a viral decline of more than 1.0 log at day 3 combined with viral load of less than 5.0 log IU/ml at day 28 predicted SVR with NPV=100% and PPV=100%. AA had significantly (P<0.01) slower HCV VK as compared to Caucasians. However, peg-IFN2b concentrations and PK parameters, peg-IFN2b max and peg-IFN2b half-life, were similar in both groups and did not predict SVR. Nevertheless, the PD parameter Ec50, estimated from non-linear fitting of the viral kinetics together with peg-IFN2b concentration data, showed that HIV/HCV co-infected AA have lower sensitivity to interferon-alpha thus giving rise to slower viral decline. The combined PK/PD parameter IFNmax/Ec90 was excellent predictor of SVR, thus showing the importance to maintain peg-IFN2b levels above Ec90 to achieve successful treatment. Further studies are needed to evaluate whether these pharmacodynamical predictions are a result of differential host response to peg-IFN2b or other viral factors conferring relative resistance to peg-IFN2b