Slowing of Peripheral Nerve Conduction Velocity in Children and Adolescents With Type 1 Diabetes Is Predicted by Glucose Fluctuations.

Unlabelled: Nerve conduction velocity (NCV) abnormalities are the forerunners of diabetic peripheral neuropathy (DPN). Therefore, this study aimed to analyze the effect of glucose profile quality on NCV in children and young adults with type 1 diabetes. Fifty-three children age 5 to 23 years with type 1 diabetes were recruited to participate in the study, which was conducted prospectively at the Children's Hospital of Eastern Switzerland from 2016 to 2022.

Home visits to identify the roles lifestyle and stress play in families of children with obesity.

One-sixth of Swiss children are affected by overweight, and despite the implementation of an evidence-based multiprofessional approach, there has only been moderate therapeutic success. An unfavourable home environment and psychosocial stresses on the family may impede lifestyle changes. This longitudinal observational study included children with obesity (body mass index [BMI] ≥97th percentile [P.

mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice.

The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in .

Effects of a novel mobile health intervention compared to a multi-component behaviour changing program on body mass index, physical capacities and stress parameters in adolescents with obesity: a randomized controlled trial.

Background: Less than 2% of overweight children and adolescents in Switzerland can participate in multi-component behaviour changing interventions (BCI), due to costs and lack of time. Stress often hinders positive health outcomes in youth with obesity. Digital health interventions, with fewer on-site visits, promise health care access in remote regions; however, evidence for their effectiveness is scarce.

Modeling of levothyroxine in newborns and infants with congenital hypothyroidism: challenges and opportunities of a rare disease multi-center study.

Modeling of retrospectively collected multi-center data of a rare disease in pediatrics is challenging because laboratory data can stem from several decades measured with different assays. Here we present a retrospective pharmacometrics (PMX) based data analysis of the rare disease congenital hypothyroidism (CH) in newborns and infants. Our overall aim is to develop a model that can be applied to optimize dosing in this pediatric patient population since suboptimal treatment of CH during the first 2 years of life is associated with a reduced intelligence quotient between 10 and 14 years.

The mechano-sensitive response of β1 integrin promotes SRC-positive late endosome recycling and activation of Yes-associated protein.

Yes-associated protein (YAP) signaling has emerged as a crucial pathway in several normal and pathological processes. Although the main upstream effectors that regulate its activity have been extensively studied, the role of the endosomal system has been far less characterized. Here, we identified the late endosomal/lysosomal adaptor MAPK and mTOR activator (LAMTOR) complex as an important regulator of YAP signaling in a preosteoblast cell line.

Phosphorylation of Merlin by Aurora A kinase appears necessary for mitotic progression.

Although Merlin's function as a tumor suppressor and regulator of mitogenic signaling networks such as the Ras/rac, Akt, and Hippo pathways is well-documented, in mammals as well as in insects, its role during cell cycle progression remains unclear. In this study, using a combination of approaches, including FACS analysis, time-lapse imaging, immunofluorescence microscopy, and co-immunoprecipitation, we show that Ser-518 of Merlin is a substrate of the Aurora protein kinase A during mitosis and that its phosphorylation facilitates the phosphorylation of a newly discovered site, Thr-581. We found that the expression in HeLa cells of a Merlin variant that is phosphorylation-defective on both sites leads to a defect in centrosomes and mitotic spindles positioning during metaphase and delays the transition from metaphase to anaphase.

Evaluating a childhood obesity program with the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework.

Primary care providers can use behavioral lifestyle interventions to effectively treat children with overweight and obesity, but implementing these interventions is challenging. Most childhood obesity intervention evaluation studies focus on effectiveness. Few studies describe implementation.

Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures.

Objective: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood.

Targeted next-generation sequencing for differential diagnosis of neurofibromatosis type 2, schwannomatosis, and meningiomatosis.

Background: Clinical overlap between neurofibromatosis type 2 (NF2), schwannomatosis, and meningiomatosis can make clinical diagnosis difficult. Hence, molecular investigation of germline and tumor tissues may improve the diagnosis.

Methods: We present the targeted next-generation sequencing (NGS) of NF2, SMARCB1, LZTR1, SMARCE1, and SUFU tumor suppressor genes, using an amplicon-based approach.

β1 integrin-dependent Rac/group I PAK signaling mediates YAP activation of Yes-associated protein 1 (YAP1) via NF2/merlin.

Cell adhesion to the extracellular matrix or to surrounding cells plays a key role in cell proliferation and differentiation and is critical for proper tissue homeostasis. An important pathway in adhesion-dependent cell proliferation is the Hippo signaling cascade, which is coregulated by the transcription factors Yes-associated protein 1 (YAP1) and transcriptional coactivator with PDZ-binding motif (TAZ). However, how cells integrate extracellular information at the molecular level to regulate YAP1's nuclear localization is still puzzling.

Linear stapled gastrojejunostomy results in fewer strictures compared to circular stapled gastrojejunostomy in laparoscopic gastric bypass surgery.

Purpose: Currently, there are two laparoscopic stapling techniques to perform the gastrojejunostomy in gastric bypass surgery: the linear stapling and circular stapling techniques. The aim of the study was to compare the two techniques regarding postoperative morbidity and weight loss at an accredited bariatric reference center in Switzerland.

Methods: We compared two consecutive cohorts at a single institution between November 2012 and June 2014 undergoing laparoscopic gastric bypass surgery.

Non-Virilizing Congenital Adrenal Hyperplasia in a Female Patient with a Novel HSD3B2 Mutation.

Classic 3β-hydroxysteroid dehydrogenase type 2 (3β-HSD II) deficiency causes congenital adrenal hyperplasia with glucocorticoid, mineralocorticoid, and sex steroid deficiency. We present a female patient with congenital adrenal hyperplasia detected in newborn screening due to elevated 17OH-progesterone. Female external genitalia and non-measurable androgen levels elicited the suspicion of a defect early in the steroid cascade.

AMOTL1 Promotes Breast Cancer Progression and Is Antagonized by Merlin.

The Hippo signaling network is a key regulator of cell fate. In the recent years, it was shown that its implication in cancer goes well beyond the sole role of YAP transcriptional activity and its regulation by the canonical MST/LATS kinase cascade. Here we show that the motin family member AMOTL1 is an important effector of Hippo signaling in breast cancer.

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.

Proteomic screening identifies a YAP-driven signaling network linked to tumor cell proliferation in human schwannomas.

Background: Inactivation of the NF2 gene predisposes to neurofibromatosis type II and the development of schwannomas. In vitro studies have shown that loss of NF2 leads to the induction of mitogenic signaling mediated by receptor tyrosine kinases (RTKs), MAP kinase, AKT, or Hippo pathways. The goal of our study was to evaluate the expression and activity of these signaling pathways in human schwannomas in order to identify new potential therapeutic targets.

[Options and limits in the treatment of overweight children and adolescents and their families in primary care].

The general practitioner or pediatrician mostly is the first point of contact for overweight children and may recognize adiposity early enough in order to start therapy of obesity or comorbidity or to initiate measures of prevention. Interventions against overweight are most efficient before age 7 in terms of short-and long-term results and should not be delayed. As obesity requires care of the entire family, close or recurring contact with the overweight child and its family is important as well as the treatment nearby their residence.

Insulinoma: only in adults?-case reports and literature review.

Insulinomas first presenting as refractory seizure disorders are well documented in adulthood but rarely found in children. Only a few cases of childhood insulinoma have been reported so far. We report on two adolescents with hyperinsulinaemic hypoglycaemia, initially misdiagnosed as epilepsy and migraine accompagnée, and compare those to other cases published.

Comorbidities in overweight children and adolescents: do we treat them effectively?

Objective: The aim was to analyze the effectiveness of treatment concerning obesity-associated comorbidities in clinical practice.

Methods: A total of 11,681 overweight children with ≥ 6-month follow-up treated at 175 centers specialized in pediatric obesity care in Central Europe were included in this analysis (mean body mass index (BMI) 29.0 ± 5.

[Recommendations on the quality of life of dependent elderly people].

The French national agency for the assessment and quality of social and medical-social institutes and services (ANESM) recently published recommendations aiming to promote the quality of life of elderly people in nursing homes. These recommendations take into account the specific characteristics of the quality of life of this sector of the population.

Does obesity lead to a specific lipid disorder? Analysis from the German/Austrian/Swiss APV registry.

Overweight and obese youth represent a challenge for the affected individual, the healthcare system as well as society as a whole. Increased long-term cardiovascular risk is one of the major consequences of early-onset obesity, affecting both life expectancy and quality of life. The aim of this report is to study the effects of age, gender and obesity category on the presence of individual components of dyslipidemia using normal-weight subjects from the population-based German KIGGS study including 17,641 randomly selected children and adolescents, aged 0-18 years (11,110 normal-weight subjects with lipid measurements) and the German-Austrian-Swiss APV registry, including 57,239 overweight or obese children, adolescents and young adults from 162 specialized obesity care centers (lipid measurements available in 29,711 subjects).