Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype.

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally.

A novel CYP17A1 deletion causes a functional knockout of the steroid enzyme 17-hydroxylase and 17,20-lyase in a Turkish family and illustrates the precise role of the CYP17A1 gene.

A novel homozygous long-range deletion of the CYP17A1 gene abolished protein expression and caused the severest form of 17-hydroxylase deficiency in one kindred of a Turkish family. The affected subjects presented with 46,XY sex reversal and 46,XX lack of pubertal development as well as severe hypertension.

Acute S100B in serum is associated with cognitive symptoms and memory performance 4 months after paediatric mild traumatic brain injury.

Objective: This study explored whether acute serum marker S100B is related with post-concussive symptoms (PCS) and neuropsychological performance 4 months after paediatric mild traumatic brain injury (mTBI).

Research Design And Methods: This prospective short-term longitudinal study investigated children (aged 6-16 years) with mTBI (n = 36, 16 males) and children with orthopaedic injuries (OI, n = 27, 18 males) as a control group. S100B in serum was measured during the acute phase and was correlated with parent-rated PCS and neuropsychological performance 4 months after the injury.

Functional evidence for continued alveolarisation in former preterms at school age?

Prematurity is the most common disruptor of lung development. The aim of our study was to examine the function of the more vulnerable peripheral airways in former preterm children by multiple-breath washout (MBW) measurements.86 school-aged children, born between 24 and 35 weeks of gestation and 49 term-born children performed nitrogen MBW.

Health-Related Quality of Life of Young Adults Treated with Recombinant Human Growth Hormone during Childhood.

Background: Since recombinant human growth hormone (rhGH) became available in 1985, the spectrum of indications has broadened and the number of treated patients increased. However, long-term health-related quality of life (HRQoL) after childhood rhGH treatment has rarely been documented. We assessed HRQoL and its determinants in young adults treated with rhGH during childhood.

The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts.

U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches. A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53 preschoolers with mild/moderate wheeze in a cross-sectional study. Despite high-dose treatment, the severe cohorts had more severe exacerbations compared with the mild/moderate ones (annual medians: school-aged 3.

Italo-Swiss "Chalk and blackboard interactive 2-day workshop"-participants feedback.

Ten "chalk and blackboard interactive workshops" have taken place between 2011 and 2015 in Southern Switzerland or Italy. Students, residents and expert pediatricians meet during 2 days and discuss 10-15 cases. Pediatricians promote reasoning, provide supporting information and correct statements.

Clinical characteristics and outcomes in children hospitalised with pandemic influenza A/H1N1/09 virus infection – a nationwide survey by the Pediatric Infectious Diseases Group of Switzerland.

Objective: To describe all patients admitted to children's hospitals in Switzerland with a diagnosis of influenza A/H1N1/09 virus infection during the 2009 influenza pandemic, and to analyse their characteristics, predictors of complications, and outcome.

Methods: All patients ≤18-years-old hospitalised in eleven children's hospitals in Switzerland between June 2009 and January 2010 with a positive influenza A/H1N1/09 reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal specimen were included.

Results: There were 326 PCR-confirmed patients of whom 189 (58%) were younger than 5 years of age, and 126 (38.

Impact of Software Settings on Multiple-Breath Washout Outcomes.

Background And Objectives: Multiple-breath washout (MBW) is an attractive test to assess ventilation inhomogeneity, a marker of peripheral lung disease. Standardization of MBW is hampered as little data exists on possible measurement bias. We aimed to identify potential sources of measurement bias based on MBW software settings.

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations.

Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.

LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases.

Background: Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking.

Methods: We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification.

Alternative outcomes for the multiple breath washout in children with CF.

Background: The lung clearance index (LCI) measured by multiple-breath washout (MBW) has been proposed as an outcome for clinical trials; however, MBW is time consuming and LCI can be affected by breathing pattern. We aimed to evaluate moment ratios and abbreviated LCI in school-aged children with mild-to-moderate CF lung disease.

Methods: Using existing data from three studies we assessed the sensitivity of moment ratios and abbreviated LCIs to (i) detect mild-to-moderate CF lung disease and (ii) detect treatment effects after 4 weeks of hypertonic saline or dornase alfa inhalation.

Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study.

Background: Niemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The objective of this retrospective cohort study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up in the Swiss NP-C cohort.

Methods: Clinical, biochemical and genetic data were assessed for 14 patients derived from 9 families diagnosed with NP-C between 1994 and 2013.

Post-concussive symptoms and neuropsychological performance in the post-acute period following pediatric mild traumatic brain injury.

Objective: There is evidence that children after mild traumatic brain injuries (mTBI) suffer ongoing post-concussive symptoms (PCS). However, results concerning neuropsychological outcome after mTBI are controversial. Thus, our aim was to examine group differences regarding neuropsychological outcome and PCS.

Salt intake in children and its consequences on blood pressure.

Sodium is the most abundant extracellular cation and therefore pivotal in determining fluid balance. At the beginning of life, a positive sodium balance is needed to grow. Newborns and preterm infants tend to lose sodium via their kidneys and therefore need adequate sodium intake.

Human NR5A1/SF-1 mutations show decreased activity on BDNF (brain-derived neurotrophic factor), an important regulator of energy balance: testing impact of novel SF-1 mutations beyond steroidogenesis.

Context: Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus.

Feasibility of automated slope III and Scond analysis in children.

Background: Multiple breath washout (MBW) derived Scond is an established index of ventilation inhomogeneity. Time-consuming post hoc calculations of the expirogram's slope of alveolar phase III (SIII) and the lack of available software hampered widespread application of Scond.

Methods: Seventy-two school-aged children (45 with cystic fibrosis; CF) performed 3 nitrogen MBW.

Pharmacogenomics of human P450 oxidoreductase.

Cytochrome P450 oxidoreductase (POR) supports reactions of microsomal cytochrome P450 which metabolize drugs and steroid hormones. Mutations in POR cause disorders of sexual development. P450 oxidoreductase deficiency (PORD) was initially identified in patients with Antley-Bixler syndrome (ABS) but now it has been established as a separate disorder of sexual development (DSD).

Taste acceptability of pulverized brand-name and generic drugs containing amlodipine or candesartan.

Trials with pulverized brand-name antihypertensive drugs suggest that, from the perspective of taste acceptability, crushed candesartan, chlortalidon, hydrochlorothiazide, lercanidipine and lisinopril should be preferred to pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan, ramipril, telmisartan and valsartan. Brand-name antihypertensive drugs and the corresponding generic medicines have never been compared with respect to their taste acceptability. We therefore investigated among healthy health care workers the taste acceptability of a pulverized 1 mg-test dose of the brand-name and two generics containing either the dihydropyridine calcium-channel blocker amlodipine (Norvasc(®), Amlodipin-Mepha(®) and Amlodipin Pfizer(®)) or the angiotensin receptor antagonist candesartan (Atacand(®), Cansartan-Mepha(®) and Pemzek(®)).

Coping is excellent in Swiss Children with inflammatory bowel disease: results from the Swiss IBD cohort study.

Background: Inflammatory bowel disease (IBD) starting during childhood has been assumed to impair quality of life (QoL) of affected children. As this aspect is crucial for further personality development, the health-related quality of life (HRQOL) was assessed in a Swiss nationwide cohort to obtain detailed information on the fields of impairment.

Methods: Data were prospectively acquired from pediatric patients included in the Swiss IBD Cohort Study.

Abnormal small airways function in children with mild asthma.

Background: Small airways disease is a hallmark in adults with persistent asthma, but little is known about small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, with an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched control subjects.

Methods: The primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test.

STAR splicing mutations cause the severe phenotype of lipoid congenital adrenal hyperplasia: insights from a novel splice mutation and review of reported cases.

Objective: The steroidogenic acute regulatory protein (StAR) transports cholesterol to the mitochondria for steroidogenesis. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired synthesis of adrenal and gonadal steroids causing adrenal insufficiency, 46,XY disorder of sex development (DSD) and failure of pubertal development. Partial loss of StAR activity may cause adrenal insufficiency only.