D-glyceric aciduria due to GLYCTK mutation: Disease or non-disease?

D-glyceric aciduria (DGA) is caused by D-glycerate-2-kinase deficiency due to biallelic pathogenic variants in It is associated with variable neurological symptoms. DGA is extremely rare, and genetic variants are only known in 7 previously described patients. We report a new patient with DGA and a novel homozygous variant.

Discovery of potent dihydro-oxazinoquinolinone inhibitors of GuaB for the treatment of tuberculosis.

Tuberculosis is the leading cause of death from an infectious disease, and is caused by Mycobacterium tuberculosis (M.tb). More than 1 billion people worldwide are thought to harbor an M.

The expanding clinical and genetic spectrum of DYNC1H1-related disorders.

Intracellular trafficking involves an intricate machinery of motor complexes including the dynein complex to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains as well as cytoplasmic light and intermediate chains have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons.

Global expression patterns of -genes in tomato and potato.

Introduction: As key-players of plant immunity, the proteins encoded by resistance genes (-genes) recognize pathogens and initiate pathogen-specific defense responses. The expression of some -genes carry fitness costs and therefore inducible immune responses are likely advantageous. To what degree inducible resistance driven by -genes is triggered by pathogen infection is currently an open question.

SMDT1 variants impair EMRE-mediated mitochondrial calcium uptake in patients with muscle involvement.

Ionic calcium (Ca) is a key messenger in signal transduction and its mitochondrial uptake plays an important role in cell physiology. This uptake is mediated by the mitochondrial Ca uniporter (MCU), which is regulated by EMRE (essential MCU regulator) encoded by the SMDT1 (single-pass membrane protein with aspartate rich tail 1) gene. This work presents the genetic, clinical and cellular characterization of two patients harbouring SMDT1 variants and presenting with muscle problems.

Normal range of intraoperative three-dimensionally derived right ventricular free-wall strain in coronary artery bypass surgery patients.

Background: Data on intraoperative three-dimensionally derived right ventricular free-wall strain (3D-RV FWS) is sparse.

Objectives: We sought to evaluate the normal range of intraoperative 3D-RV FWS in patients scheduled for coronary artery bypass graft (CABG) surgery and compared to conventional echocardiographic parameters. Prospective observational study.

Biallelic variants in PIGN cause Fryns syndrome, multiple congenital anomalies-hypotonia-seizures syndrome, and neurologic phenotypes: A genotype-phenotype correlation study.

Purpose: Biallelic PIGN variants have been described in Fryns syndrome, multiple congenital anomalies-hypotonia-seizure syndrome (MCAHS), and neurologic phenotypes. The full spectrum of clinical manifestations in relation to the genotypes is yet to be reported.

Methods: Genotype and phenotype data were collated and analyzed for 61 biallelic PIGN cases: 21 new and 40 previously published cases.

Integrated genomic surveillance enables tracing of person-to-person SARS-CoV-2 transmission chains during community transmission and reveals extensive onward transmission of travel-imported infections, Germany, June to July 2021.

BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.

The role of the efflux transporter, P-glycoprotein, at the blood-brain barrier in drug discovery.

The blood-brain barrier (BBB) expresses a high abundance of transporters, particularly P-glycoprotein (P-gp), that regulate endogenous and exogenous molecule uptake and removal of waste. This review discusses key drug metabolism and pharmacokinetic considerations for the efflux transporter P-gp at the BBB in drug discovery and development. We highlight the differences in P-gp expression and protein levels across species but the limited observations of species-specific substrates.

Drug clearance by aldehyde oxidase: can we avoid clinical failure?

Despite increased awareness of aldehyde oxidase (AO) as a major drug-metabolising enzyme, predicting the pharmacokinetics of its substrates remains challenging. Several drug candidates have been terminated due to high clearance, which were subsequently discovered to be AO substrates. Even retrospective extrapolation of human clearance, from models more sensitive to AO activity, often resulted in underprediction.

The role of base-rate neglect in cyberchondria and health anxiety.

Cyberchondria is characterized by excessive health-related online search behavior associated with an unfounded escalation of concerns about common symptomatology. It often co-occurs with health anxiety. We investigated whether base-rate neglect-the cognitive bias to ignore a priori probabilities (e.

A proof of concept using the Ussing chamber methodology to study pediatric intestinal drug transport and age-dependent differences in absorption.

Little is known about the impact of age on the processes governing human intestinal drug absorption. The Ussing chamber is a system to study drug transport across tissue barriers, but it has not been used to study drug absorption processes in children. This study aimed to explore the feasibility of the Ussing chamber methodology to assess pediatric intestinal drug absorption.

Winners and losers of the COVID-19 pandemic: An excess profits tax proposal.

In this paper, we study the gains and losses incurred during the COVID-19 pandemic. We distinguish between the effects of the pandemic and those of the health measures implemented to reduce the death toll, notably "the lockdown." Our theoretical model is focused on within-sector firm heterogeneity and involves imperfect competition in a partial equilibrium setting.

Cost-Effectiveness of Nintedanib for Patients with Progressive Fibrosing Interstitial Lung Disease (PF-ILD).

Objectives: Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by increased pulmonary fibrosis, lung function decline, acute exacerbations, decreased quality of life and increased mortality. Nintedanib may slow down disease progression, but long-term outcomes are unknown. We aimed to assess the cost-effectiveness of nintedanib in comparison to placebo, both on top of usual care in patients with PF-ILD.

PIGN encephalopathy: Characterizing the epileptology.

Objective: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy.

Methods: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment.

Cell wall thickenings and tylosoid: developmental morphology reveals novelties for secretory canals in Protium ovatum (Burseraceae).

We investigated the structure, histochemistry, and ultrastructure of the secretory canals in the vegetative axis of Protium ovatum from a developmental perspective. Samples of roots, stems, and leaves were analyzed using light and transmission electron microscopy. Secretory canals composed of a uniseriate epithelium and a wide lumen occurred in the phloem of all analyzed organs.

Ontogeny of Small Intestinal Drug Transporters and Metabolizing Enzymes Based on Targeted Quantitative Proteomics.

Most drugs are administered to children orally. An information gap remains on the protein abundance of small intestinal drug-metabolizing enzymes (DMEs) and drug transporters (DTs) across the pediatric age range, which hinders precision dosing in children. To explore age-related differences in DMEs and DTs, surgical leftover intestinal tissues from pediatric and adult jejunum and ileum were collected and analyzed by targeted quantitative proteomics for apical sodium-bile acid transporter, breast cancer resistance protein (BCRP), monocarboxylate transporter 1 (MCT1), multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein (MRP) 2, MRP3, organic anion-transporting polypeptide 2B1, organic cation transporter 1, peptide transporter 1 (PEPT1), CYP2C19, CYP3A4, CYP3A5, UDP glucuronosyltransferase (UGT) 1A1, UGT1A10, and UGT2B7.

Perioperative Two-Dimensional Left Ventricular Global Longitudinal Strain in Coronary Artery Bypass Surgery: A Prospective Observational Pilot Study.

Objectives: There are limited data on perioperative left ventricular strain. The authors aimed to describe the entire perioperative course of two-dimensional left ventricular global longitudinal strain in patients undergoing coronary artery bypass graft (CABG) surgery and compare to common parameters of LV function assessment.

Design: Prospective observational study.

Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients Are Not Affected by Extracorporeal Membrane Oxygenation: A Matched Cohort Analysis.

Existing evidence is inconclusive whether meropenem dosing should be adjusted in patients receiving extracorporeal membrane oxygenation (ECMO). Therefore, the aim of this observational matched cohort study was to evaluate the effect of ECMO on pharmacokinetic (PK) variability and target attainment (TA) of meropenem. Patients admitted to the intensive care unit (ICU) simultaneously treated with meropenem and ECMO were eligible.