Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis can be a contributor to short stature. One such mutation can occur in the ACAN gene, causing short stature and advanced bone age. Similarly, mutations in growth hormone receptors (GHR) can lead

Long-term outcomes of hematopoietic stem cell transplantation (HSCT) in children with juvenile metachromatic leukodystrophy (MLD) have been investigated systematically, while short-term effects of HSCT on the course of the disease remain to be elucidated. In this study, the clinical course was evaluated over the first 24 months following HSCT, conducted at our center in 12 children with juvenile MLD

Hyperoxia is a well-known cause of cerebral white matter injury in preterm infants with male sex being an independent and critical risk factor for poor neurodevelopmental outcome. Sex is therefore being widely considered as one of the major decisive factors for prognosis and treatment of these infants. But unfortunately, we still lack a clear view of the molecular mechanisms that lead to such a profound

Osteogenesis imperfecta (OI) is a rare congenital disease with a wide spectrum of severity characterized by skeletal deformity and increased bone fragility as well as additional, variable extraskeletal symptoms. Here, we present an overview of the genetic heterogeneity and pathophysiological background of OI as well as OI-related bone fragility disorders and highlight current therapeutic options. The

Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by mutations in the active 21-hydroxylase gene (CYP21A2). The clinical symptoms can vary greatly. To date, no systematic studies have been undertaken in Germany. Description of the phenotype, evaluation of the diagnostics and genotype-phenotype correlation Retrospective analysis of the data of 134 patients (age range

Biomarkers which predict future health outcomes are key to the goals of precision health. Such biomarkers do not have to be involved in the causal pathway of a disease, and their performance is best assessed using statistical tests of clinical performance and evaluation of net health impact. DNA methylation is the most commonly studied epigenetic process and represents a potential biomarker of future

The postnatal intestinal colonization of human milk-fed and formula-fed infants differs substantially, as does the susceptibility to infectious diseases during infancy. Specific ingredients in human milk, such as prebiotic human milk oligosaccharides and a specifically structured fat composition with high proportion of beta-palmitic acid (beta-PA) promote the growth of intestinal bifidobacteria, which

Febrile neutropenia is a common and serious complication during treatment of childhood cancer. Empirical broad-spectrum antibiotics are usually administered until neutrophil cell count recovery. It was the aim of this study to investigate cytokine profiles as potential biomarkers using in-vitro sepsis models to differentiate between distinct clinical courses of febrile neutropenia (FN). We conducted

To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1

Optoacoustic imaging (OAI), or photoacoustic imaging (PAI), has fundamentally influenced basic science by providing high-resolution visualization of biological mechanisms. With the introduction of multispectral optoacoustic tomography (MSOT), these technologies have now moved closer to clinical applications. MSOT utilizes short-pulsed near-infrared laser light to induce thermoelastic expansion in targeted

X chromosome inactivation (XCI) is an indispensable process in the development of human female embryos. Reportedly, XCI occurs when a blastocyst contains 10–12 embryonic progenitor cells. To date, it remains unclear whether XCI ratios are normally preserved in Klinefelter syndrome (KS) patients with 47,XXY karyotype. We examined XCI ratios in 18 KS patients through DNA methylation analysis for the

The impairment of nephrogenesis is caused by noxae, all of which are significantly different in molecular composition. These can cause an early termination of nephron development in preterm and low birth weight babies resulting in oligonephropathy. For the fetal human kidney, there was no negative effect reported on the early stages of nephron anlage such as the niche, pretubular aggregate, renal vesicle

Neonate immune cell functions lack full protection against pathogens. This could be either defect or protective mechanism against overshooting proinflammatory immune responses. We here analysed the function of classical, pro- and anti-inflammatory monocytes and granulocytes from neonates in comparison with adults to investigate if suppressed functions of subpopulations are causative for the unique

In Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whether the corresponding health benefits in vegetarians outweigh the risks of nutrient deficiencies has not been fully clarified. It should be noted that vegetarians often have a higher socioeconomic

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major healthcare burden. Despite great progresses in perinatal medicine over the past decades, no cure for BPD has been found. The complex pathophysiology of the disease further hampers the development of effective treatment strategies, but recent insights into the biology of mesenchymal stem (MSCs) and progenitor

BACKGROUND Alveologenesis is the last stage in lung development and is essential for building the gas-exchanging units called alveoli. Despite intensive lung research, the intricate crosstalk between mesenchymal and epithelial cell lineages during alveologenesis is poorly understood. This crosstalk contributes to the formation of the secondary septae, which are key structures of healthy alveoli. CONCLUSIONS

Asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) are all chronic pulmonary diseases, albeit with different etiologies, that are characterized by airflow limitation, chronic inflammation, and abnormal mucus production/rheology. Small synthetic molecule-based therapies are commonly prescribed for all three diseases. However, there has been increased interest in "biologicals"

After birth, adequate lung function is necessary for the successful adaptation of a preterm baby. Both prenatal and postnatal insults and therapeutic interventions have an immediate effect on lung function and gas exchange but also interfere with fetal and neonatal lung development. Prenatal insults like chorioamnionitis and prenatal interventions like maternal glucocorticosteroids interact but might

The maintenance of oxygen homeostasis in human tissues is mediated by several cellular adaptations in response to low-oxygen stress, called hypoxia. A decrease in tissue oxygen levels is initially counteracted by increasing local blood flow to overcome diminished oxygenation and avoid hypoxic stress. However, studies have shown that the physiological oxygen concentrations in several tissues are much

Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have

Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils

Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial

Incomplete intestinal absorption of fructose might lead to abdominal complaints such as pain, flatulence and diarrhoea. Whether defect fructose transporters such as GLUT5 or GLUT2 are involved in the pathogenesis of fructose malabsorption is a matter of debate. The hydrogen production by colonic bacteria is used for diagnosis with the hydrogen breath test. However, the appropriate fructose test dose

Bacterial infection often leads to cellular damage, primarily marked by loss of cellular integrity and cell death. However, in recent years, it is being increasingly recognized that, in individual cells, there are graded responses collectively termed cell-autonomous defense mechanisms that induce cellular processes designed to limit cell damage, enable repair, and eliminate bacteria. Many of these

BACKGROUND Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Some gliadin peptides are not digested by intestinal proteases and can have different biological effects. Gliadin peptides can induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides

Irritable bowel syndrome (IBS) is a common condition with a complex and largely unknown etiology. There is no cure, and treatment options are mainly directed to the amelioration of symptoms. IBS causes reduced quality of life and poses considerable repercussions on health and socioeconomic systems. There is a heritable component in IBS, and genetic research is a valuable tool for the identification

Perinatal complications in both term- and preterm-born infants are a leading cause of neonatal morbidities and mortality. Infants face different challenges in the neonatal intensive care unit with long-term morbidities such as perinatal brain injury and bronchopulmonary dysplasia being particularly devastating. While advances in perinatal medicine have improved our understanding of the pathogenesis

Primary sucrase-isomaltase deficiency, originally thought to be a homozygous recessive disorder, has been found to have numerous genetic variants that alone or in combination (compound heterozygosity) express varying degrees of clinical illness, most commonly causing chronic diarrhea, abdominal pain, and bloating. These symptoms are also present with secondary sucrase-isomaltase deficiency. Recent

UNLABELLED ᅟ: Starch requires six enzymes for digestion to free glucose: two amylases (salivary and pancreatic) and four mucosal maltase activities; sucrase-isomaltase and maltase-glucoamylase. All are deficient in suckling rodents. OBJECTIVE The objective of this study is to test (13)C-starch digestion before weaning by measuring enrichment of blood (13)C-glucose in maltase-glucoamylase-null and wild-type

Microvillus inclusion disease (MVID) is characterised by onset of intractable life-threatening watery diarrhoea during infancy. Transmission electron microscopy demonstrates shortening or absence of apical microvilli, pathognomonic microvillus inclusions in mature enterocytes and subapical accumulation of periodic acid-Schiff-positive granules or vesicles confirming diagnosis. Mutations in MYO5B have

Osmotic diarrhea and abdominal pain in humans are oftentimes associated with carbohydrate malabsorption in the small intestine due to loss of function of microvillar disaccharidases. Disaccharidases are crucial for the digestion and the subsequent absorption of carbohydrates. This review focuses on sucrase-isomaltase as the most abundant intestinal disaccharidase and the primary or induced pathological

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestine. IBD is a multifactorial disorder, and IBD-associated genes are critical in innate immune response, inflammatory response, autophagy, and epithelial barrier integrity. Moreover, epithelial oxygen tension plays a critical role in intestinal inflammation and resolution in IBD. The intestines have a dynamic and

BACKGROUND Atopic dermatitis constitutes a most burdensome chronic inflammatory skin disease. Standard treatment is cumbersome and often targets its main symptom, pruritus, only insufficiently. FINDINGS Recent advances in our understanding of the role of histamine and its four receptors suggest new approaches which target the histamine receptors alone or as combination therapies to more efficiently

Despite continuous improvements in treating clinical symptoms and the identification of single compounds that effectively rescue some rare mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), associated lung and liver pathologies remain largely untreatable and no real breakthrough is visible for the majority of patients suffering from cystic fibrosis (CF).Novel compounds have

BACKGROUND Childhood arterial ischemic stroke (CAIS) is increasingly recognized as an important cause of significant long-term morbidity in the pediatric population. Post stroke movement disorders, above all hemi-dystonias, are much more common in children after stroke compared to adults. However, research in this field is largely lacking. By highlighting some important knowledge gaps, we aim to encourage

Asthma is a clinically heterogeneous disorder, whose onset and progression results from a complex interplay between genetic susceptibility, allergens, and viral triggers. Sphingolipids and altered sphingolipid metabolism have emerged as potential key contributors to the pathogenesis of asthma. Orosomucoid-like 3 gene (ORMDL3) and the asthma susceptibility locus 17q21 have been strongly and reproducibly

BACKGROUND Intestinal monocytes/macrophages sustain the intestinal immune homeostasis and might be an attractive therapeutic target for the management of inflammatory bowel disease (IBD). Granulocyte macrophage colony-stimulating factor (GM-CSF) exerts beneficial effects on intestinal inflammation and promotes signal transducer and activator of transcription 3 (STAT3)-mediated expansion of myeloid-derived

BACKGROUND The immunogenicity and limited stability of conventional messenger RNA (mRNA) has traditionally restricted its potential therapeutic use. In 1992, the first clinical application of mRNA was reported as a potential protein-replacement therapy; however, subsequent investigations have not been made for almost two decades. Recent developments, including increased stability, controlling immunogenicity

Protein homeostasis describes the tight supervision of protein synthesis, correct protein maturation and folding, as well as the timely disposal of unwanted and damaged proteins by the ubiquitin-proteasome pathway or the lysosome-autophagy route. The cellular processes involved in preservation of protein homeostasis are collectively called proteostasis. Dysregulation of proteostasis is an emerging

BACKGROUND Most cancer therapies are devised for adult or even elder patients. However, when dealing with pediatric cancers, additional considerations are needed. CONCLUSIONS This review discusses non-classic components of tumors and highlights possible treatment approaches which might be of particular benefit for children and adolescents.

BACKGROUND Fanconi anemia is one of the best studied inherited cancer-prone diseases. Greatly improved protocols for hematopoietic stem cell transplantation increasingly save the lives of these young patients. However, in both transplanted and not transplanted patients, the emergence of aggressive squamous cell carcinoma represents a major medical challenge. CONCLUSIONS This mini review summarizes

BACKGROUND MicroRNAs (miRNAs) are crucial regulators of human immunity e.g. against Mycobacterium tuberculosis. Against the background of still alarming high mortality of tuberculosis effective biomarkers to improve diagnosis of M. tuberculosis infection and successful treatment are of major importance. CONCLUSIONS This review summarizes recent surrogate tissue studies for identification of miRNA biomarker

Therapeutic hypothermia is an effective cytoprotectant and promising intervention shown to improve outcome in patients following cardiac arrest and neonatal hypoxia-ischemia. However, despite our clinical and experimental experiences, the protective molecular mechanisms of therapeutic hypothermia remain to be elucidated. Therefore, in this brief overview we discuss both the clinical evidence and molecular

Matrix metalloproteinases are vital drivers of synaptic remodeling in health and disease. It is suggested that at early stages of epileptogenesis, inhibition of matrix metalloproteinases may help ameliorate cell death, aberrant network rewiring, and neuroinflammation and prevent development of epilepsy.

BACKGROUND Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) is the most common disorder of mitochondrial β-oxidation of long-chain fatty acids. In order to maintain glucose homeostasis, the kidney and liver as the main gluconeogenic organs play an important role under conditions of impaired fatty acid oxidation. However, little is known about how a defective fatty acid oxidation machinery

Congenital leptin deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the leptin gene. This review describes the molecular and cellular characteristics of the eight distinct mutations found so far in humans.

BACKGROUND Stent implantation into the tracheo-bronchial system may be life-saving in selected pediatric patients with otherwise intractable stenosis of the upper airways. Following implantation, significant tissue proliferation may occur, requiring re-interventions. We sought to evaluate the effect of immunosuppressive coating of the stents on the extent of tissue proliferation in an animal model

Cystic fibrosis is a mono-genetic multi-system disease; however, respiratory manifestations cause the main morbidity and mortality where chronic bacterial infections lead to bronchiectasis and ultimately respiratory failure. Metabolomics allows a relatively complete snapshot of metabolic processes in a sample using different mass spectrometry methods. Sample types used for discovery of biomarkers or

Childhood obesity and incidence of asthma are increasing globally. The parallel increase of the two suggests that obesity and asthma may be related and that abnormalities in the lipid and/or glucose metabolism may contribute to the pathogenesis of asthma. The clinical presentation of obese asthma is distinct from other asthma phenotypes and depending on age of onset of symptoms. Asthma in obese people

BACKGROUND Primary cilia are membrane-bound microtubule-based protuberances of the cell membrane projecting to the extracellular environment. While little attention was paid to this subcellular structure over a long time, recent research has highlighted multiple cellular functions of primary cilia and has brought cilia to the focus of medical and cell biological research. FINDINGS Cilia are nowadays

BACKGROUND Mutations in known causative genes and cytogenetically detectable chromosomal rearrangements account for a fraction of cases with 46,XY disorders of sex development (DSD). Recent advances in molecular cytogenetic technologies, including array-based comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA), have enabled the identification of copy-number

BACKGROUND Sodium channels predominantly expressed in brain are expressed in myocardial tissue and play an important role in cardiac physiology. Alterations of sodium channels are known to result in neurological disease in infancy and childhood. It will be of interest to study the expression of brain-type sodium channels in the developing myocardium. METHODS The expression of neuronal sodium channels

BACKGROUND Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia. METHODS Forty-four late preterm lambs underwent total umbilical

Chitin, after cellulose, the second most abundant biopolymer on earth, is a key component of insects, fungi, and house-dust mites. Lower life forms are endowed with chitinases to defend themselves against chitin-bearing pathogens. Unexpectedly, humans were also found to express chitinases as well as chitinase-like proteins that modulate immune responses. Particularly, increased levels of the chitinase-like

Neonatal chronic lung disease in the preterm infant, i.e. bronchopulmonary dysplasia (BPD) is characterized by impaired pulmonary development with its effects persisting into adulthood. Triggered in the immature lung by infectious complications, oxygen toxicity and the impact of mechanical ventilation, a sustained inflammatory response, extensive remodeling of the extracellular matrix, increased apoptosis

BACKGROUND MicroRNA (miRNA) and messenger RNA (mRNA) expression differs in cystic fibrosis (CF) versus non-CF bronchial epithelium. Here, the role of miRNA in basal regulation of the transcription factor ATF6 was investigated in bronchial epithelial cells in vitro and in vivo. METHODS Using in silico analysis, miRNAs predicted to target the 3'untranslated region (3'UTR) of the human ATF6 mRNA were

BACKGROUND AND FINDINGS Perinatal programming, i.e., the (epigenetic) modification of (genetic) functions throughout lifetime, suffers from the notion of premature theories and difficult and extensive research strategies. CONCLUSIONS This mini review aims at depicting 9 current developments and discusses possible future research strategies.