Comparative activity of carbapenem testing (the COMPACT study) in Turkey

<p>Abstract</p> <p>Background</p> <p>Recent evidence indicates that Gram-negative bacterial pathogens, the most common of which are <it>Pseudomonas </it>spp., <it>Enterobacteriaceae</it>, and <it>Acinetobacter baumannii</it>, are frequent causes of hospital-acquired infections. This study aims to evaluate the in vitro activity of doripenem and comparator carbapenem antibiotics against Gram-negative clinical isolates collected from COMParative Activity of Carbapenem Testing (COMPACT) study centres in Turkey.</p> <p>Methods</p> <p>Ten centres in Turkey were invited to submit <it>Pseudomonas aeruginosa</it>, <it>Enterobacteriaceae</it>, and other Gram-negative isolates from intensive care unit (ICU)/non-ICU patients with complicated intra-abdominal infections, bloodstream infections, or nosocomial pneumonia, including ventilator-associated pneumonia, between May and October 2008. Susceptibility was determined by each centre using E-test. A central laboratory performed species confirmation as well as limited susceptibility and quality-control testing.</p> <p>Results</p> <p>Five hundred and ninety six isolates were collected. MIC₉₀values for doripenem, meropenem, and imipenem, respectively, were 32, ≥ 64, and ≥ 64 mg/L against <it>Pseudomonas </it>spp.; 0.12, 0.12, and 0.5 mg/L against <it>Enterobacteriaceae</it>; and ≥ 64 mg/L for each against other Gram-negative isolates. In determining the susceptibility of hospital isolates of selected Gram-negative pathogens to doripenem, imipenem, and meropenem, we found that against all pathogens combined, the MIC₉₀for ICU compared with non-ICU isolates was higher.</p> <p>Conclusions</p> <p>Doripenem showed similar or slightly better activity than meropenem and better activity than imipenem against the Gram-negative pathogens collected in Turkey.</p

Primary aldosteronism: A Japanese perspective

Primary aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 10% of all hypertension. Far from being benign, hypertension due to PA is associated with high cardiovascular morbidity and mortality. However, PA is still underdiagnosed in general practice. Recent reports strongly recommend that identifying patients with PA is cost-beneficial based on improved cardiovascular outcomes afforded by specific surgical and medical treatment. This review provides an update of PA including controversial aspects of diagnosis and treatment

Structure-Activity Relationship of Cinnamaldehyde Analogs as Inhibitors of AI-2 Based Quorum Sensing and Their Effect on Virulence of Vibrio spp

Background: Many bacteria, including Vibrio spp., regulate virulence gene expression in a cell-density dependent way through a communication process termed quorum sensing (QS). Hence, interfering with QS could be a valuable novel antipathogenic strategy. Cinnamaldehyde has previously been shown to inhibit QS-regulated virulence by decreasing the DNA-binding ability of the QS response regulator LuxR. However, little is known about the structure-activity relationship of cinnamaldehyde analogs. Methodology/Principal Findings: By evaluating the QS inhibitory activity of a series of cinnamaldehyde analogs, structural elements critical for autoinducer-2 QS inhibition were identified. These include an alpha, beta unsaturated acyl group capable of reacting as Michael acceptor connected to a hydrophobic moiety and a partially negative charge. The most active cinnamaldehyde analogs were found to affect the starvation response, biofilm formation, pigment production and protease production in Vibrio spp in vitro, while exhibiting low cytotoxicity. In addition, these compounds significantly increased the survival of the nematode Caenorhabditis elegans infected with Vibrio anguillarum, Vibrio harveyi and Vibrio vulnificus. Conclusions/Significance: Several new and more active cinnamaldehyde analogs were discovered and they were shown to affect Vibrio spp. virulence factor production in vitro and in vivo. Although ligands for LuxR have not been identified so far, the nature of different cinnamaldehyde analogs and their effect on the DNA binding ability of LuxR suggest that these compounds act as LuxR-ligands

Exploración vocacional en adolescentes: evaluación de una intervención en clase

Analisa-se o impacto de uma intervenção psicológica na exploração e tomada de decisão vocacional em adolescentes portugueses. Em contexto curricular e de classe, desenvolveram-se actividades de exploração do meio e do Eu com 39 alunos e 43 alunas do 9o ano, entre 13 e 17 anos (M=14,4, DP=0,95). Em um design pré/pós-teste, aplicaram-se o Career Exploration Survey (CES) e o Career Decision Difficulties Questionnaire (CDDQ). Os resultados do teste do sinal evidenciaram ganhos significativos (p<0,01) nas dimensões de exploração e diminuição significativa da falta de informação profissional (p<0,01) e do total das dificuldades de decisão (p<0,05). Observou-se um padrão de correlações negativas (ró de Spearman) entre as duas medidas vocacionais, evidenciando uma relação entre a informação explorada na intervenção e a diminuição das dificuldades de decisão por falta de motivação. Em geral, os resultados suportam a importância do papel da exploração da carreira na diminuição das dificuldades de tomada de decisão.This study analyses the impact of a psychological intervention to promote vocational exploration and decisionmaking in Portuguese adolescents. Activities to foster exploration of self and environment were developed in a classroom program with 39 boys and 43 girls, all 9th grade students, between 13 and 17 years of age (M=14,4, SD=0.95). Following a pre/post-test design, the Career Exploration Survey (CES), and the Career Decision Difficulties Questionnaire (CDDQ) were administered. Results of sign-test showed significant increments (p<0.01) in all of the exploration dimensions, significant reduction of lack of occupational information (p<0.01) and of the total of career decision-making difficulties (p<0.05). Negative correlations (Spearman’s rho) between the two career measures was observed, evidencing a relationship between information explored during intervention and decreased difficulty with decision-making due to lack of motivation. In general, results support the importance of career exploration on diminishing decision-making difficulties.Evalúa-se el impacto de una intervención psicológica que fomenta la exploración y la decisión vocacional en adolescentes portugueses. Fueran efectuadas actividades de exploración del medio ambiente y del yo en contexto curricular de clase con 39 alumnos y 43 alumnas del curso 3º ESO, 13 hasta 17 años (M=14,4, DP=0,95). Utilizó-se un diseño pre/posteste, con aplicación del Career Exploration Survey (CES) y Career Decision Difficulties Questionnaire (CDDQ). Resultados del test del señal evidencian beneficios significativos (p<0,01) en las dimensiones de la exploración, reducción significativa de ausencia de información ocupacional (p<0,01) y total de dificultades de decisión (p<0,05). Ha sido observado un patrón de correlaciones negativas (ró de Spearman) entre las dos medidas vocacionales, mostrando relación entre la información explorada e la disminución de las dificultades de decisión por falta de motivación. En general, resultados sostienen la importancia de la exploración de carrera en la disminución de las dificultades de decisió

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

PURPOSE: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. METHODS: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. RESULTS: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10-18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10-13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. CONCLUSION: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing