An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients.

To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved.

Vascular alterations among male elite athletes recovering from SARS-CoV-2 infection.

SARS-CoV-2 may affect the cardiovascular system and vascular impairment has been reported in healthy young adults recovering from COVID-19. However, the impact of SARS-CoV-2 infection on the vascular function of elite athletes is unknown. We examined 30 healthy male elite athletes (age 25.

Recommendations for whole genome sequencing in diagnostics for rare diseases.

In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions.

Strategies and Bottlenecks in Hexaploid Wheat to Mobilize Soil Iron to Grains.

Our knowledge of iron (Fe) uptake and mobilization in plants is mainly based on and rice. Although multiple players of Fe homeostasis have been elucidated, there is a significant gap in our understanding of crop species, such as wheat. It is, therefore, imperative not only to understand the different hurdles for Fe enrichment in tissues but also to address specifically the knowns/unknowns involved in the plausible mechanism of Fe sensing, signaling, transport, and subsequent storage in plants.

Phase Angle Is a Stronger Predictor of Hospital Outcome than Subjective Global Assessment-Results from the Prospective Dessau Hospital Malnutrition Study.

This prospective cohort study of 16,943 consecutive patients compared phase angle (PhA, foot-to-hand at 50 kHz) and subjective global assessment (SGA) to predict outcomes length of hospital stay (LOS) and in-hospital mortality in patients at risk of malnutrition (NRS-2002 ≥ 3). In 1505 patients, the independent effects on LOS were determined by competing risk analysis and on mortality by logistic regression. In model I, including influence factors age, sex, BMI, and diagnoses, malnourished (SGA B and C) patients had a lower chance for a regular discharge (HR 0.

Peri-intubation Cardiovascular Collapse in Patients Who Are Critically Ill: Insights from the INTUBE Study.

Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e.

Novel Liposomal Rolipram Formulation for Clinical Application to Reduce Emesis.

Introduction: The phosphodiesterase 4 (PDE4) inhibitor, rolipram, has beneficial effects on tissue inflammation, injury and fibrosis, including in the liver. Since rolipram elicits significant CNS side-effects in humans (ie, nausea and emesis), our group developed a fusogenic lipid vesicle (FLV) drug delivery system that targets the liver to avoid adverse events. We evaluated whether this novel liposomal rolipram formulation reduces emesis.

Reproducibility of strength performance and strength-endurance profiles: A test-retest study.

The present study was designed to evaluate the test-retest consistency of repetition maximum tests at standardized relative loads and determine the robustness of strength-endurance profiles across test-retest trials. Twenty-four resistance-trained males and females (age, 27.4 ± 4.

Clinical and genetic characterization of a cohort of 97 CLN6 patients tested at a single center.

Background: Ceroid lipofuscinoses neuronal 6 (CLN6) disease belongs to the neuronal ceroid lipofuscinoses (NCLs), complex and genetically heterogeneous disorders with wide geographical and phenotypic variation. The first clinical signs usually appear between 18 months and 8 years, but examples of later-onset have also been reported. Common manifestations include ataxia, seizures, vision impairment, and developmental regression.

Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia.

Objective: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (Mendelian Inheritance in Man # 615683).

Putting the pieces together: Cognitive correlates of self-derivation of new knowledge in elementary school classrooms.

A central goal of development and formal education is to build a knowledge base. Accumulating knowledge relies, in part, on self-derivation of new semantic knowledge via integration of separate yet related learning episodes. Previous tests of self-derivation evidence both age-related and significant individual variability in self-derivation performance in the laboratory and the classroom due in part to individual differences in verbal comprehension (children and adults) and working memory (adults only).

Inhibitory Response to CK II Inhibitor Silmitasertib and CDKs Inhibitor Dinaciclib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines.

Casein kinase II (CK2) and cyclin-dependent kinases (CDKs) frequently interact within multiple pathways in pancreatic ductal adenocarcinoma (PDAC). Application of CK2- and CDK-inhibitors have been considered as a therapeutic option, but are currently not part of routine chemotherapy regimens. We investigated ten PDAC cell lines exposed to increasing concentrations of silmitasertib and dinaciclib.

The Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 and Buparlisib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines.

The aberrant activation of the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathway is common in pancreatic ductal adenocarcinomas (PDAC). The application of inhibitors against PI3K and AKT has been considered as a therapeutic option. We investigated PDAC cell lines exposed to increasing concentrations of MK-2206 (an AKT1/2/3 inhibitor) and Buparlisib (a pan-PI3K inhibitor).

Identification of 27 Novel Variants in Genes , and in Lithuanian Families With Alport Syndrome.

Introduction: Alport syndrome (AS) is an inherited disorder characterized by hematuria, proteinuria, and kidney function impairment, and frequently associated with extrarenal manifestations. Pathogenic variants in usually cause X-linked Alport syndrome (XLAS), whereas those in the or genes are associated with autosomal dominant (AD) or recessive (AR) inheritance. To date, more than 3000 different disease-causing variants in , and have been identified.

Diabetic ketoacidosis, cerebral venous sinus thrombosis and fulminant cerebral oedema in COVID-19 infection complicated by infection.

We present an unusual case of a woman in her 30s who was admitted for diabetic ketoacidosis (DKA) in the setting of newly diagnosed but late COVID-19 infection with associated infection. Her altered mental status, out of proportion with her metabolic decompensation, revealed a superimposed cerebral venous sinus thrombosis (CVST) with fulminant cerebral oedema and ultimately brain death. This unusual and fulminant case of cerebral oedema in the setting of COVID-19 infection with bacterial infection, DKA and CVST was the perfect storm with multiple interwoven factors.

Metabolomic Study Using Time-of-Flight Mass Spectrometry Reveals Novel Urinary Biomarkers for Gaucher Disease Type 1.

Gaucher disease (GD) is a lysosomal storage disorder resulting from a biallelic mutation in the gene , leading to deficiencies in the enzyme β-glucocerebrosidase (Gcase). Inabilities of the Gcase to catabolize its substrate result in the accumulation of sphingolipids in macrophages, which impairs the cell functions and ultimately leads to multisystemic clinical manifestations. Important variability in symptoms and manifestations may lead to challenging diagnosis and patient care.

Tracking cortical excitability dynamics with transcranial magnetic stimulation in focal epilepsy.

Introduction: The lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS-EMG) to track dynamical changes in cortical excitability on a within-subject basis.

Methods: We recruited people with refractory focal epilepsy who underwent video-EEG monitoring and drug tapering as part of the presurgical evaluation.

Epidemiology and Trends in Survival of Systemic Sclerosis in Olmsted County (1980-2018): A Population-based Study.

Background/purpose: To update the epidemiology of systemic sclerosis (SSc) and evaluate the performance of the ACR/EULAR 2013 vs. 1980 ARA classification criteria in a U.S.

Alterations in the Experience of Time, Space, and Intersubjectivity and the Interaction with Pre-Existent Psychopathology during the COVID-19 Pandemic.

Background: The COVID-19 pandemic and the measures to protect the physically vulnerable may disproportionately affect people with mental health vulnerabilities, who receive psychotherapeutic inpatient treatment, as many of these measures impact the (inter)subjective space crucial to psychotherapy.

Objective: We investigate how people with pre-existing mental health conditions and healthcare professionals experienced changes linked to the COVID-19 pandemic.

Methods: During the first COVID-19 outbreak and lockdown in spring 2020, we conducted semi-structured interviews with patients and healthcare professionals at a clinic for psychosomatic medicine in Germany and analyzed them following the principles of descriptive phenomenology focusing on social interactions, intersubjectivity, and the therapeutic space.

Evaluation of Eosinophilic Cationic Protein as a Marker of Alveolar and Cystic Echinococcosis.

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus . In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein of eosinophilic granulocytes, against . Therefore, the main objective of this study was to evaluate ECP as a biomarker in the treatment of alveolar echinococcosis (AE) and cystic echinococcosis (CE).