Perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular no Brasil

Background and objectives

Malignant hyperthermia is an autosomal dominant hypermetabolic pharmacogenetic syndrome, with a mortality rate of 10%‐20%, which is triggered by the use of halogenated inhaled anesthetics or muscle relaxant 10%‐20% succinylcholine. The gold standard for suspected susceptibility to malignant hyperthermia is the in vitro muscle contracture test in response to halothane and caffeine. The determination of susceptibility in suspected families allows the planning of safe anesthesia without triggering agents for patients with known susceptibility to malignant hyperthermia by positive in vitro muscle contracture test. Moreover, the patient whose suspicion of malignant hyperthermia was excluded by the in vitro negative muscle contracture test may undergo standard anesthesia. Susceptibility to malignant hyperthermia has a variable manifestation ranging from an asymptomatic subject presenting a crisis of malignant hyperthermia during anesthesia with triggering agents to a patient with atrophy and muscle weakness due to central core myopathy. The aim of this study is to analyze the profile of reports of susceptibility to malignant hyperthermia confirmed with in vitro muscle contracture test.

Pictures on My Analyst's Walls: Reflections on the Art of Käthe Kollwitz,the Nazis and the Art of Psychoanalysis

The author's reaction to the sight of two of the works of the German expressionist artist Käthe Kollwitz on the walls of the rooms of her prospective training analyst forms the starting point for an exploration of art, totalitarianism and the art of psychoanalysis. The art and life of Kollwitz are used as the basis of an attempt to grasp the meaning of art together with how and why art can speak so powerfully to us. The impact of the Nazi regime on Kollwitz and her contemporaries leads to consideration of the totalitarian view of the purpose of art and consequently what we mean by ‘art’. Finally, the author perceives the art of Kollwitz as a life‐long self‐analysis and considers this as a mirror to the concept of psychoanalysis as an art. In her exploration of the arts she applies Bion's concept of ‘O’ (the thing‐in‐itself) and its transformations to understand and give meaning to the arts.     

Exact Gradients Improve Parameter Estimation in Nonlinear Mixed Effects Models with Stochastic Dynamics

Nonlinear mixed effects (NLME) modeling based on stochastic differential equations (SDEs) have evolved into a promising approach for analysis of PK/PD data. SDE-NLME models go beyond the realm of standard population modeling as they consider stochastic dynamics, thereby introducing a probabilistic perspective on the state variables. This article presents a summary of the main contributions to SDE-NLME models found in the literature. The aims of this work were to develop an exact gradient version of the first-order conditional estimation (FOCE) method for SDE-NLME models and to investigate whether it enabled faster estimation and better gradient precision/accuracy compared to the use of gradients approximated by finite differences. A simulation-estimation study was set up whereby finite difference approximations of the gradients of each level were interchanged with the exact gradients. Following previous work, the uncertainty of the state variables was accounted for using the extended Kalman filter (EKF). The exact gradient FOCE method was implemented in Mathematica 11 and evaluated on SDE versions of three common PK/PD models. When finite difference gradients were replaced by exact gradients at both FOCE levels, relative runtimes improved between 6- and 32-fold, depending on model complexity. Additionally, gradient precision/accuracy was significantly better in the exact gradient case. We conclude that parameter estimation using FOCE with exact gradients can successfully be applied to SDE-NLME models.     

Geno- and Phenotypic Characterization of Human Cytomegalovirus Mutants Selected In Vitro after Letermovir (AIC246) Exposure

Letermovir is a novel antiviral compound currently in clinical development for the prevention of human cytomegalovirus (HCMV) infections. In contrast to all currently approved anti-HCMV drugs that target the viral DNA polymerase, letermovir acts via a distinct mode of action involving the viral terminase subunit pUL56. To extend our understanding of potential letermovir resistance mechanisms, we used marker transfer to characterize mutations identified in letermovir-resistant HCMV variants that were selected in cell culture.     

Effectiveness of preoperative breathing exercise interventions in patients undergoing cardiac surgery: A systematic review

Postoperative pulmonary complications are a common cause of morbidity and mortality in patients undergoing cardiac surgery, leading to an increase in length of hospital stay and healthcare costs.This systematic literature review aims to determine whether patients undergoing cardiac surgery who undergo preoperative breathing exercise training have better postoperative outcomes such as respiratory parameters, postoperative pulmonary complications, and length of hospital stay.Systematic searches were performed in the CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Clinical Answers, Cochrane Database of Systematic Reviews, MEDLINE and MedicLatina databases. Studies were included if they examined adult patients scheduled for elective cardiac surgery, who underwent a preoperative breathing exercise training aimed at improving breathing parameters, preventing postoperative pulmonary complications, and reducing hospital length of stay. This systematic review was based on Cochrane and Prisma statement recommendations in the design, literature search, analysis, and reporting of the review.The search yielded 608 records. Eleven studies met the inclusion criteria. Ten studies were randomized controlled trials and one was an observational cohort study. Data from 1240 participants was retrieved from these studies and meta-analysis was performed whenever possible.A preoperative breathing intervention on patients undergoing cardiac surgery may help improve respiratory performance after surgery, reduce postoperative pulmonary complications and hospital length of stay. However, more trials are needed to support and strengthen the evidence.     

Are linear measurements and computerized volumetric ratios determined from axial MRI useful for diagnosing hydrocephalus in children with tuberculous meningitis?

Purpose  

This study aimed to evaluate linear measurements and computerized volumetric ratios on axial magnetic resonance imaging (MRI) scans against the diagnosis of hydrocephalus in children with tuberculous meningitis (TBM).