Fingolimod in children with Rett syndrome: the FINGORETT study.

Background: Rett syndrome (RS) is a severe neurodevelopmental disorder for which there is no approved therapy. This study aimed to assess safety and efficacy of oral fingolimod in children with RS using a pre-post and case-control design.

Methods: At the University of Basel Children's Hospital, Basel, Switzerland, children with RS were included if they were older than 6 years and met the established diagnostic criteria of RS, including a positive MeCP2 mutation.

Optimal allocation of limited test resources for the quantification of COVID-19 infections.

The systematic identification of infected individuals is critical for the containment of the COVID-19 pandemic. Currently, the spread of the disease is mostly quantified by the reported numbers of infections, hospitalisations, recoveries and deaths; these quantities inform epidemiology models that provide forecasts for the spread of the epidemic and guide policy making. The veracity of these forecasts depends on the discrepancy between the numbers of reported, and unreported yet infectious, individuals.

Changes of Conformation in Albumin with Temperature by Molecular Dynamics Simulations.

This work presents the analysis of the conformation of albumin in the temperature range of 300 K - 312 K , i.e., in the physiological range.

MedPath: A process-based modeling language for designing care pathways.

Context: Medical professionals and hospitals promote solutions like care pathways and Health Information Systems (HIS) to support medical conduct and improve the quality of medical care.

Purpose: This study proposes MedPath: a Domain Specific Language (DSL) for modeling care pathways based on the paradigms of Model-Based Engineering (MBE) that can be integrated into software solutions.

Procedures: We have developed MedPath's abstract syntax with the Eclipse Modeling Framework by employing Ecore technology and concrete syntax with the Eclipse Sirius.

Developmental differences in genome replication program and origin activation.

To ensure error-free duplication of all (epi)genetic information once per cell cycle, DNA replication follows a cell type and developmental stage specific spatio-temporal program. Here, we analyze the spatio-temporal DNA replication progression in (un)differentiated mouse embryonic stem (mES) cells. Whereas telomeres replicate throughout S-phase, we observe mid S-phase replication of (peri)centromeric heterochromatin in mES cells, which switches to late S-phase replication upon differentiation.

Gallbladder Cancer Presenting as Mirizzi Syndrome Complicated by Rapidly Evolving 23 rRNA Gene-Linezolid Resistance with Vancomycin-Resistant Enterococcus Infection Resulting in Fatal Cholangial Sepsis.

We describe the case of a 71-year-old woman who presented with obstructive jaundice and subhilar bile duct stenosis. MRI showed extensive cholecystolithiasis with an impacted bile stone in the cystic duct suggesting Mirizzi syndrome. Delayed enhancement of the thickened gallbladder wall suggested inflammation instead of carcinoma.

Intergenerational trauma is associated with expression alterations in glucocorticoid- and immune-related genes.

Offspring of trauma survivors are more likely to develop PTSD, mood, and anxiety disorders and demonstrate endocrine and molecular alterations compared to controls. This study reports the association between parental Holocaust exposure and genome-wide gene expression in peripheral blood mononuclear cells (PBMC) from 77 Holocaust survivor offspring and 15 comparison subjects. Forty-two differentially expressed genes (DEGs) were identified in association with parental Holocaust exposure (FDR-adjusted p < 0.

[Maternal deaths due to haemorrhage in France 2013-2015].

Maternal death from haemorrhage is decreasing: in the last 15 years the number of deaths has been halved. This improvement demonstrates the progress made in hemorrhage management as a result of collective efforts. The number of deaths in this triennium is 22, representing 8.

[Maternal deaths due to hypertensive disorders in France 2013-2015].

Between 2013 and 2015, six maternal deaths were due to hypertensive disorders. During this period, the maternal mortality ratio was 0.2/100,000 live births.

Fluorescence Microscopy-Based Quantitation of GLUT4 Translocation: High Throughput or High Content?

Due to the global rise of type 2 diabetes mellitus (T2DM) in combination with insulin resistance, novel compounds to efficiently treat this pandemic disease are needed. Screening for compounds that induce the translocation of glucose transporter 4 (GLUT4) from the intracellular compartments to the plasma membrane in insulin-sensitive tissues is an innovative strategy. Here, we compared the applicability of three fluorescence microscopy-based assays optimized for the quantitation of GLUT4 translocation in simple cell systems.

Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes.

Recent genome-wide association studies have identified over 230 genetic risk loci for multiple sclerosis. Current experimental autoimmune encephalomyelitis (EAE) models requiring active induction of disease may not be optimally suited for the characterization of the function of these genes. We have thus used gene expression profiling to study whether spontaneous opticospinal EAE (OSE) or MOG-induced EAE mirrors the genetic contribution to the pathogenesis of multiple sclerosis more faithfully.

-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal β-Glucocerebrosidase.

The scope of a series of -alkylated iminosugar based inhibitors in the d- as well as d- configuration towards their interaction with human lysosomal β-glucocerebrosidase has been evaluated. A versatile synthetic toolbox has been developed for the synthesis of -alkylated iminosugar scaffolds conjugated to a variety of terminal groups via a benzoic acid ester linker. The terminal groups such as nitrile, azide, alkyne, nonafluoro--butyl and amino substituents enable follow-up chemistry as well as visualisation experiments.

The glucose-sensing transcription factor ChREBP is targeted by proline hydroxylation.

Cellular energy demands are met by uptake and metabolism of nutrients like glucose. The principal transcriptional regulator for adapting glycolytic flux and downstream pathways like lipogenesis to glucose availability in many cell types is carbohydrate response element-binding protein (ChREBP). ChREBP is activated by glucose metabolites and post-translational modifications, inducing nuclear accumulation and regulation of target genes.

BALSAM-An Interactive Online Platform for Breath Analysis, Visualization and Classification.

The field of breath analysis lacks a fully automated analysis platform that enforces machine learning good practice and enables clinicians and clinical researchers to rapidly and reproducibly discover metabolite patterns in diseases. We present BALSAM-a comprehensive web-platform to simplify and automate this process, offering features for preprocessing, peak detection, feature extraction, visualization and pattern discovery. Our main focus is on data from multi-capillary-column ion-mobility-spectrometry.

Short and long sleep duration and associated factors in pre-adolescence and early adulthood: evidence from the 1993 Pelotas birth cohort study.

Objective: The objective of the present study was to investigate the associated factors with short and long sleep duration at ages 11 (pre-adolescence) and 22 years old (early adulthood).

Methods: Participants of the 1993 Pelotas birth cohort with self-reported sleep records at 11 (n = 4442) and 22 (n = 3800) years were included. The total sleep time duration was categorised as short (<9 h for 11 years and <7 h for 22 years), long (>11 for 11 years and >9 for 22 years) and recommended according to the National Sleep Foundation criteria.

American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Foundation Guide to Enhance Otologic and Neurotologic Care During the COVID-19 Pandemic.

: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19.

Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes and -5a-Substituted Derivatives of 4--Isofagomine.

Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid β-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the potent β-d-galactosidase inhibitor 4--isofagomine. Structure-activity relationships were investigated by X-ray crystallography as well as by alterations in the cyclopentane moiety such as deoxygenation and replacement by fluorine of a "strategic" hydroxyl group.

Characterisation of pulmonary function trajectories: results from a Brazilian cohort.

Background: Pulmonary function (PF) trajectories are determined by different exposures throughout the life course. The aim of this study was to investigate characteristics related to PF trajectories from 15 to 22 years in a Brazilian cohort.

Methods: A birth cohort study (1993 Pelotas Birth Cohort) was conducted with spirometry at 15, 18 and 22 years.

Rapid recovery of carbon cycle processes after the cessation of chronic nutrient enrichment.

Salt marshes provide critical ecosystem services including some of the highest rates of carbon storage on Earth. However, many salt marshes receive very high nutrient loads and there is a growing body of evidence indicating that this nutrient enrichment alters carbon cycle processes. While many restoration plans prioritize nutrient management in their efforts to conserve salt marsh ecosystems, there has been little empirical investigation of the capacity for carbon cycle processes to recover once nutrient loading is reduced.

Drug-drug and drug-food interactions in an infant with early-onset SCN2A epilepsy treated with carbamazepine, phenytoin and a ketogenic diet.

Sodium channel 2 subunit α (SCN2A) mutations cause difficult-to-treat early-onset epilepsy. Effective treatment includes high-dose phenytoin or carbamazepine ± ketogenic diet (KD). We describe an infant with early-onset SCN2A-epilepsy with subtherapeutic carbamazepine concentration during transition from phenytoin treatment to avoid long-term neurotoxicity.

Transcriptome network of the papillary thyroid carcinoma radiation marker CLIP2.

Background: We present a functional gene association network of the CLIP2 gene, generated by de-novo reconstruction from transcriptomic microarray data. CLIP2 was previously identified as a potential marker for radiation induced papillary thyroid carcinoma (PTC) of young patients in the aftermath of the Chernobyl reactor accident. Considering the rising thyroid cancer incidence rates in western societies, potentially related to medical radiation exposure, the functional characterization of CLIP2 is of relevance and contributes to the knowledge about radiation-induced thyroid malignancies.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

Health-related quality of life, self-reported impairments and activities of daily living in relation to muscle function in post-polio syndrome.

Background: The symptoms of post-polio syndrome (PPS) and its resulting disabilities can affect quality of life and the ability to perform daily activities. No study has comprehensively analysed how various patient-reported outcome measures (PROMs) are associated with objectively assessed physical function in patients with PPS.

Aim: To investigate health-related quality of life (HRQOL), self-reported impairments and activities of daily living during 6 months and evaluate their association with clinical muscle function outcomes in individuals with PPS.