The Risk of Nonsteroidal Anti-Inflammatory Drugs in Pediatric Medicine: Listen Carefully to Children with Pain.

Over the last decades, the use of over-the-counter analgesics in the general population has increased in Germany. Ibuprofen is one of the most commonly used nonsteroidal anti-inflammatory drug (NSAID) and is frequently prescribed to children as an analgesic and/or antipyretic. Besides having a well-established safety and efficacy profile when used in appropriate doses, cases of NSAID-induced acute kidney injury (AKI) have been described in the pediatric population, particularly in the context of dehydration and in combination with other drugs.

Potentials and current shortcomings in the cooperation between German centers for rare diseases and primary care physicians: results from the project TRANSLATE-NAMSE.

Background: The TRANSLATE-NAMSE project with the strengthening of the centers for rare diseases with their affiliation to the European Reference Networks was a major step towards the implementation of the German National Plan of Action for People with Rare Diseases establishing better care structures. As primary care physicians, general practitioners and pediatricians play a central role in the diagnosis of patients with rare disease, as it is usually them referring to specialists and rare disease centers. Therefore, the interface management between primary care physicians and the centers for rare diseases is of particular importance.

An Integrated clinical pathway for diagnosis, treatment and care of rare diseases: model, operating procedures, and results of the project TRANSLATE-NAMSE funded by the German Federal Joint Committee.

Background: Diagnosis, treatment, and care of patients with rare diseases require multidisciplinary cooperation between medical and paramedical specialities and with patients and families. Innovative genetic diagnostics, whole exome and whole genome sequencing (WES, WGS) has enlarged the diagnostic toolkit but also increased the complexity of the endeavour. Structured multidisciplinary clinical pathways (CPW) can guide diagnosis, treatment, and care of patients with rare diseases, link scientific evidence to clinical practice and optimise clinical outcomes whilst maximising clinical efficiency.

Generation of an induced pluripotent stem cell line (DHMCi006-A) from a patient with autosomal recessive polycystic kidney disease (ARPKD) carrying a compound heterozygous missense mutation in the fibrocystin encoding PKHD1 gene.

Mutations in the PKHD1 gene, encoding for the ciliary protein fibrocystin, play a major role in the cystogenesis in autosomal recessive polycystic kidney disease (ARPKD), a severe pediatric kidney disorder. Peripheral blood mononuclear cells (PBMCs) from a female patient carrying a compound heterozygous PKHD1 mutation (c.6331A>G(;)7717C>T) were obtained and reprogrammed by viral transduction using the Cytotune®-iPS 2.

Generation of an induced pluripotent stem cell line (DHMCi007-A) from a patient with autosomal recessive polycystic kidney disease (ARPKD) carrying a homozygous missense mutation in the fibrocystin-encoding PKHD1 gene.

Autosomal recessive polycystic kidney disease (ARPKD) is a severe pediatric kidney disorder primarily caused by mutations in the fibrocystin-encoding PKHD1 gene. It is characterized by the progressive development of cysts, eventually leading to renal failure. In order to create patient specific iPSCs, peripheral blood mononuclear cells (PBMCs) from a female patient carrying a homozygous PKHD1 mutation (c.

Differences of Phenylalanine Concentrations in Dried Blood Spots and in Plasma: Erythrocytes as a Neglected Component for This Observation.

Monitoring phenylalanine (Phe) concentrations is critical for the management of phenylketonuria (PKU). This can be done in dried blood spots (DBS) or in EDTA plasma derived from capillary or venous blood. Different techniques are used to measure Phe, the most common being flow-injection analysis tandem mass spectrometry (FIA-MS-MS) and ion exchange chromatography (IEC).

H-NMR-based metabolic profiling identifies non-invasive diagnostic and predictive urinary fingerprints in 5q spinal muscular atrophy.

Background: 5q spinal muscular atrophy (SMA) is a disabling and life-limiting neuromuscular disease. In recent years, novel therapies have shown to improve clinical outcomes. Yet, the absence of reliable biomarkers renders clinical assessment and prognosis of possibly already affected newborns with a positive newborn screening result for SMA imprecise and difficult.

Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings.

Congenital disorders of glycosylation (CDGs) form a group of rare diseases characterized by hypoglycosylation. We here report the identification of 16 individuals from nine families who have either inherited or de novo heterozygous missense variants in STT3A, leading to an autosomal-dominant CDG. STT3A encodes the catalytic subunit of the STT3A-containing oligosaccharyltransferase (OST) complex, essential for protein N-glycosylation.

Effects of Exercise Interventions on Immune Function in Children and Adolescents With Cancer and HSCT Recipients - A Systematic Review.

Background: Pediatric cancer patients are at high risk for life-threatening infections, therapy associated complications and cancer-related side effects. Exercise is a promising tool to support the immune system and reduce inflammation. The primary objective of this systematic review was to evaluate the effects of exercise interventions in pediatric cancer patients and survivors on the immune system.

Enhanced Antiviral Function of Magnesium Chloride-Modified Heparin on a Broad Spectrum of Viruses.

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium.

A Systematic Review of the Safety, Feasibility and Benefits of Exercise for Patients with Advanced Cancer.

Exercise therapy is a common supportive strategy in curative cancer treatment with strong evidence regarding its positive effects on, for example, cancer-related fatigue, health- related quality of life, and physical function. In the field of advanced cancer patients, knowledge about exercise as a useful supportive strategy is missing. The aim of this systematic review was to evaluate the feasibility and safety of exercise interventions as well as its effects on lowering the symptom burden.

Diagnostic Performance of SARS-CoV-2 Rapid Antigen Test in a Large, German Cohort.

We assessed the performance of a rapid antigen test (RAT) in everyday clinical practice. Between 1 November 2020 until 1 April 2021 all in-patients at the Helios University Hospital Wuppertal, Germany, as well as the accompanying relatives at the Children's Hospital received a SARS-CoV-2 RAT and a SARS-CoV-2 RT-PCR prior to admission. Out of 3686 patients, 22 (0.

Mitochondrial damage in renal epithelial cells is potentiated by protein exposure in propionic aciduria.

Propionic aciduria (PA) is caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). Due to inefficient propionate catabolism patients are endangered by life-threatening ketoacidotic crisis. Protein and amino acid restriction are major therapeutic pillars.

Human Species D Adenoviruses Isolated from Diarrheal Feces Show Low Infection Rates in Primary Nasal Epithelial Cells.

The importance of adenovirus (Ad) research is significantly increasing with respect to virotherapy for vaccine development, tumor, and gene therapy. Due to the different species and subtypes of this virus, the characterization of the biological significance of especially rare Ad is necessary. Previously, rare Ad types 70, 73, and 74 were originally isolated from fecal samples of immunocompromised patients and they represent recombinants of other Ad types.

Childhood-onset hereditary spastic paraplegia and its treatable mimics.

Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common "mimics" of cerebral palsy. Early detection of these heterogenous genetic disorders can inform genetic counseling, anticipatory guidance, and improve outcomes, particularly where specific treatments exist. The diagnosis relies on clinical pattern recognition, biochemical testing, neuroimaging, and increasingly next-generation sequencing-based molecular testing.

Biceps Femoris Long Head Muscle Fascicles Actively Lengthen During the Nordic Hamstring Exercise.

Current debate exists around whether a presumed eccentric exercise, the Nordic hamstring exercise (NHE), actually causes active hamstring muscle lengthening. This is because of the decoupling that can occur between the muscle fascicle and muscle-tendon unit (MTU) length changes in relatively compliant human lower-limb MTUs, which results in MTU lengthening not necessarily causing muscle fascicle lengthening. This missing knowledge complicates the interpretation of why the NHE is effective at reducing running-related hamstring muscle injury risk in athletes previously unfamiliar with performing this exercise.

A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation.

Defects in the evolutionarily conserved protein-glycosylation machinery during embryonic development are often fatal. Consequently, congenital disorders of glycosylation (CDG) in human are rare. We modelled a putative hypomorphic mutation described in an alpha-1,3/1,6-mannosyltransferase (ALG2) index patient (ALG2-CDG) to address the developmental consequences in the teleost medaka (Oryzias latipes).

The mystery behind the nostrils - technical clues for successful nasal epithelial cell cultivation.

Objectives: Research involving the nose reveals important information regarding the morphology and physiology of the epithelium and its molecular response to agents. The role of nasal epithelial cells and other cell subsets within the nasal epithelium play an interesting translational split between experimental and clinical research studying respiratory disorders or pathogen reactions. With an additional technical manuscript including a detailed description of important technical aspects, tips, tricks, and nuances for a successful culturing of primary, human nasal epithelial cells (NAEPCs), we here aim to improve the process of communication between experimentalists and physicians, supporting the purpose of a fruitful work for future translational projects.

Molecular and metabolic bases of tetrahydrobiopterin (BH) deficiencies.

Tetrahydrobiopterin (BH) deficiency is caused by genetic variants in the three genes involved in de novo cofactor biosynthesis, GTP cyclohydrolase I (GTPCH/GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS/PTS), sepiapterin reductase (SR/SPR), and the two genes involved in cofactor recycling, carbinolamine-4α-dehydratase (PCD/PCBD1) and dihydropteridine reductase (DHPR/QDPR). Dysfunction in BH metabolism leads to reduced cofactor levels and may result in systemic hyperphenylalaninemia and/or neurological sequelae due to secondary deficiency in monoamine neurotransmitters in the central nervous system. More than 1100 patients with BH deficiency and 800 different allelic variants distributed throughout the individual genes are tabulated in database of pediatric neurotransmitter disorders PNDdb.

Trimethylamine-N-Oxide Levels Are Similar in Asymptomatic vs. Symptomatic Cerebrovascular Atherosclerosis.

Trimethylamine-N-oxide (TMAO) is correlated with atherosclerosis and vascular diseases such as coronary heart disease and ischemic stroke. The aim of the study was to investigate whether TMAO levels are different in symptomatic vs. asymptomatic cerebrovascular atherosclerosis.

Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma Patients Treated with Postoperative Radiotherapy.

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models.

Transient elastography correlated to four different histological fibrosis scores in children with liver disease.

Currently, liver histology is the gold standard for the detection of liver fibrosis. In recent years, new methods such as transient elastography (TE) have been introduced into clinical practice, which allow a non-invasive assessment of liver fibrosis. The aim of the present study was to investigate the predictive value of TE for higher grade fibrosis and whether there is any relevance which histologic score is used for matching.

The spectrum of peripheral neuropathy in disorders of the mitochondrial trifunctional protein.

Peripheral neuropathy is a known irreversible long-term complication of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MTPD), two inherited disorders of mitochondrial long-chain fatty acid oxidation. The underlying pathophysiology of neuropathy is still not fully understood. We report electrophysiological studies and neurological findings in a series of 8 LCHAD-deficient and 11 MTP-deficient patients.