Double ProGlide preclose technique for vascular access closure after leadless pacemaker implantation

Journal of Interventional Cardiac Electrophysiology - The use of vascular closure devices in patients receiving the Micra leadless pacemaker may shorten time to ambulation, facilitate same-day...     

Mode of action of iron (III) chelators as antimalarials: II. Evidence for differential effects on parasite iron-dependent nucleic acid synthesis

Iron chelation treatment of red blood cells infected with Plasmodium falciparum selectively intervenes with iron-dependent metabolism of malaria parasites and inhibits their development. Highly permeant hydroxamate iron chelator RSFileum2 affects all parasite stages when cultures are continuously exposed to drug, but affects primarily ring stages when assessed for irreversible effects, ie, sustained inhibition remaining after drug removal. On the other hand, the hydrophilic and poorly permeant desferrioxamine (DFO) affects primarily trophozoite/schizont stages when tested either in the continuous mode or irreversible mode. Unlike parasites, mammalian cells subjected to similar drug treatment show complete growth recovery once drugs are removed. Our studies indicate that parasites display a limited capacity to recover from intracellular iron depletion evoked by iron chelators. Based on these findings we provide a working model in which the irreversible effects of RSFs on rings are explained by the absence of pathways for iron acquisition/utilization by early forms of parasites. Trophozoite/schizonts can partially recover from RSFileum2 treatments, but show no DNA synthesis following DFO treatment even after drug removal and iron replenishment by permeant iron carriers. At trophozoite stage, the parasite uses a limited pathway for refurnishing its iron-containing enzymes, thus overcoming iron deprivation caused by permeant RSFileum2, but not by DFO because this latter drug is not easily removable from parasites. Their DNA synthesis is blocked by the hydroxamate iron chelators probably by affecting synthesis of ribonucleotide reductase (RNRase). Presumably in parasites, prolonged repression of the enzyme leads also to irreversible loss of activity. The action profiles of RSFileum2 and DFO presented in this study have implications for improved chemotherapeutic performance by combined drug treatment and future drug design based on specific intervention at parasite DNA synthesis.     

Serum immunoglobulin G subclass responses in different phases of hepatitis E virus infection

To investigate the specific immunoglobulin (Ig) G subclass responses in patients with hepatitis E virus (HEV) infection, an open reading frame 2 (ORF2) protein based enzyme‐linked immunosorbant assay was used to measure antibody levels in sera obtained at different phases of infection. Sera were collected at 2–31 days and at 6 months after the onset of symptoms corresponding to the acute (n = 48, 100% IgM‐positive) and convalescent (n = 17/48, 53% IgM‐positive) phases of infection, respectively. IgM‐negative sera from 61 individuals infected at least ≥6 months ago (prior exposure) were also tested. IgG1, IgG2, IgG3, and IgG4 antibodies were detected in 100%, 6%, 56%, and 4% of acute phase sera, respectively, and in 100%, 0%, 0%, and 65% of convalescent phase sera, respectively. IgG1 antibody levels were significantly higher than those of the other detectable subclasses of IgG in the acute and convalescent sera (P < 0.05). The IgG3 antibodies in six acute phase patients were replaced by IgG4 antibodies in the convalescent phase of infection. Patients with prior exposure to HEV had low total IgG antibody titers and decreased IgG1 seropositivity compared with those in the acute and convalescent phases. IgG1 was the only major subclass of antibody to be detected in all the three phases of infection. Other than IgG1 antibodies, the subclass antibody response was restricted to IgG3 and IgG4 antibodies in the acute and convalescent phases of infection, respectively. J. Med. Virol. 85:828–832, 2013. © 2013 Wiley Periodicals, Inc.     

Evolution of β-catenin-independent Wnt–GSK3–mTOR signalling in regulation of energy metabolism in isoproterenol-induced cardiotoxicity model

Inflammation Research - Isoproterenol (ISO) is widely used agent to study the effects of interventions which could prevent or attenuate the development of myocardial infarction. The sequence of...     

Non-equilibrium atmospheric pressure plasma assisted degradation of the pharmaceutical drug valsartan: influence of catalyst and degradation environment

This paper investigated the degradation of the pharmaceutical drug Valsartan (VS) using non-equilibrium atmospheric pressure plasma (NEAPP) with various operating conditions. The heterogeneous photocatalyst ZnO nanoparticles (NP''s) were synthesized using a hydrothermal process. The morphology, chemical composition and structure of as-synthesized ZnO NPs were examined by Field Emission Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) analysis. Then, VS degradation was examined in three subsequent treatment conditions including plasma treatment alone, the combination of plasma with as-prepared ZnO NPs and various environments (air, oxygen and hydrogen peroxide) at fixed plasma operating potential and treatment time. The degradation efficiency of plasma-treated VS by various conditions was observed using UV-visible spectroscopy. Optical Emission Spectrometry (OES) was used to characterize the distribution and emission intensity of various reactive species (OH˙, N₂-SPS and O) during the degradation processes which plays a vital role in the degradation of VS. The role of OH˙ and H₂O₂ during the degradation process was further examined by chemical dosimetry and spectroscopic techniques. Furthermore, pH, conductivity and TOC of the untreated and plasma-treated VS were also investigated. The results on the degradation of VS showed that plasma treatment combined with ZnO NP''s has a significant effect on degradation of molecules of VS than degradation processes carried out by other experimental conditions due to the formation of higher concentrations of various reactive oxygen and nitrogen species during the degradation processes.

Degradation of valsartan by plasma combined with various environmental conditions.     

Social support a key factor for adherence to multidrug-resistant tuberculosis treatment

Background

Multidrug-resistant tuberculosis (MDR-TB) is emerging as a major public health problem globally. Treatment success rates in MDR-TB across the globe are not encouraging as completing MDR-TB treatment successfully is challenging due to high proportion of lost to follow up.

INCLEN diagnostic tool for autism spectrum disorder (INDT-ASD): Development and validation

Objective

To develop and validate INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD).

Design

Diagnostic test evaluation by cross sectional design

Setting

Four tertiary pediatric neurology centers in Delhi and Thiruvanthapuram, India.

Methods

Children aged 2–9 years were enrolled in the study. INDT-ASD and Childhood Autism Rating Scale (CARS) were administered in a randomly decided sequence by trained psychologist, followed by an expert evaluation by DSM-IV TR diagnostic criteria (gold standard).

Main outcome measures

Psychometric parameters of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency.

Results

154 children (110 boys, mean age 64.2 mo) were enrolled. The overall diagnostic accuracy (AUC=0.97, 95% CI 0.93, 0.99; P<0.001) and validity (sensitivity 98%, specificity 95%, positive predictive value 91%, negative predictive value 99%) of INDT-ASD for Autism spectrum disorder were high, taking expert diagnosis using DSM-IV-TR as gold standard. The concordance rate between the INDT-ASD and expert diagnosis for’ ASD group’ was 82.52% [Cohen’s κ=0.89; 95% CI (0.82, 0.97); P=0.001]. The internal consistency of INDT-ASD was 0.96. The convergent validity with CARS (r = 0.73, P= 0.001) and divergent validity with Binet-Kamat Test of intelligence (r = ?0.37; P=0.004) were significantly high. INDT-ASD has a 4-factor structure explaining 85.3% of the variance.

Conclusion

INDT-ASD has high diagnostic accuracy, adequate content validity, good internal consistency high criterion validity and high to moderate convergent validity and 4-factor construct validity for diagnosis of Autistm spectrum disorder.