TFIIH stabilization recovers the DNA repair and transcription dysfunctions in thermo-sensitive trichothiodystrophy.

Trichothiodystrophy (TTD) is a rare hereditary disease whose prominent feature is brittle hair. Additional clinical signs are physical and neurodevelopmental abnormalities and in about half of the cases hypersensitivity to UV radiation. The photosensitive form of TTD (PS-TTD) is most commonly caused by mutations in the ERCC2/XPD gene encoding a subunit of the transcription/DNA repair complex TFIIH.

Adherence to the Mediterranean Diet Is Associated with Better Metabolic Features in Youths with Type 1 Diabetes.

Our aim was to evaluate adherence to the Mediterranean diet (MedDiet) among children and adolescents with type 1 diabetes (T1D) in relation to metabolic control. Adherence to the MedDiet was assessed with the Mediterranean Diet Quality Index (KIDMED) questionnaire and physical activity by the International Physical Activity Questionnaire for Adolescent (IPAQ-A) on 65 subjects (32 males, 9-18 years) with T1D. Clinical and metabolic evaluation was performed (standardized body mass index (BMI-SDS), hemoglobin A1C (HbA1c), continuous glucose monitoring metrics when present, blood pressure, lipid profile).

Breakfast Skipping, Weight, Cardiometabolic Risk, and Nutrition Quality in Children and Adolescents: A Systematic Review of Randomized Controlled and Intervention Longitudinal Trials.

Breakfast skipping increases with age, and an association with a high risk of being overweight (OW) and of obesity (OB), cardiometabolic risk, and unhealthy diet regimen has been demonstrated in observational studies with children and adults. Short-term intervention trials in adults reported conflicting results. The purpose of this systematic review was to summarize the association of breakfast skipping with body weight, metabolic features, and nutrition quality in the groups of young people that underwent randomized controlled (RCT) or intervention longitudinal trials lasting more than two months.

Retrospective Diagnosis of a Novel Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature.

Short stature is a frequent disorder in the pediatric population and can be caused by multiple factors. In the last few years, the introduction of Next Generation Sequencing (NGS) in the molecular diagnostic workflow led to the discovery of mutations in novel genes causing short stature including heterozygous mutations in gene. It encodes for aggrecan, a primary proteoglycan component specific for the structure of the cartilage growth plate, articular and intervertebral disc.

Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial.

Background & Aims: Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality.

Methods: Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466).

Haptoglobin Phenotypes Are Associated with the Postload Glucose and Insulin Levels in Pediatric Obesity.

Purpose: Haptoglobin (Hp) is a protein involved in the acute-phase reaction of inflammation. Humans have three major phenotypes (Hp1-1, Hp1-2, and Hp2-2). Several studies have shown altered Hp regulation in adults with obesity and metabolic alterations.

The relationship between cortisol and IGF-I influences metabolic alteration in pediatric overweight and obesity.

Background/objective: Data on metabolic impairments in Cushing's syndrome and GH deficiency all suggest that the relationship between cortisol and GH/IGF-I axis in obesity may have a role in the related diseases. However, studies focusing only on one of these hormones are often controversial in paediatrics. We aimed to explore the simultaneous relationship between cortisol and IGF-I with the metabolic alterations in paediatric obesity.

A Systematic Review of the Association of Skipping Breakfast with Weight and Cardiometabolic Risk Factors in Children and Adolescents. What Should We Better Investigate in the Future?

The incidence of skipping breakfast in pediatric subjects is rising, and a relationship with overweight (OW) and obesity (OB) has been shown. Associations with cardiovascular outcomes and skipping breakfast in adults have been reported. The purpose of this systematic review was to summarize the association of skipping breakfast with body weight and metabolic outcomes in the pediatric population.

Adherence to the Mediterranean Diet among School Children and Adolescents Living in Northern Italy and Unhealthy Food Behaviors Associated to Overweight.

The purposes of this study were to evaluate the differences in Mediterranean diet and its components among primary and secondary school children and adolescents living in northern Italy, and the associations with the weight status. Adherence was assessed by the KIDMED (Mediterranean Diet Quality Index) questionnaire on 669 subjects (6⁻16 years) attending five schools of Novara. The adherence was poor in 16.

Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics.

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment.

[Consensus document and recommendations for the prevention of cardiovascular disease in Italy - 2018].

Cardiovascular prevention represents a cornerstone of modern strategies to reduce the burden of cardiovascular disease. It is of key importance to prevent cardiovascular diseases and associated events, not only to reduce morbidity and mortality, but also to increase the years of wellness in the aging population and to make the growing socio-economic burden imposed by cardiovascular events more sustainable.The current approach to prevention is based on an integrated use of effective lifestyle measures and, whenever appropriate, of antihypertensive and antidiabetic drugs, lipid-lowering agents and antiplatelet drugs.

High-normal estimated glomerular filtration rate and hyperuricemia positively correlate with metabolic impairment in pediatric obese patients.

Background: Childhood obesity represents a major health concern worldwide due to its well established detrimental effect on cardiovascular and its potential negative effect on kidney functions. However, biomarkers that can help diagnose early stages of kidney damage in obese children represent an unmet clinical need.

Objectives: In this study, we asked whether the prevalence of microalbuminuria, estimated glomerular filtration rate (eGFR) or hyperuricemia recorded in a wide cohort of obese children and adolescents would positively correlate with cardiometabolic dysfunction in these subjects.

Improving clinical diagnosis in SHOX deficiency: the importance of growth velocity.

BackgroundThe aim of this study was to estimate the prevalence of haploinsufficiency of short stature homeobox containing gene (SHOX) deficiency (SHOXD) in a population of short-statured children, and to analyze their phenotype and the performance of clinical scores.MethodsScreening for SHOXD was performed in 281 children with short stature by direct sequencing and multiplex ligation probe-dependent amplification. Subjects with SHOXD were compared with 117 matched short patients without SHOXD.

Insulin resistance, serum uric acid and metabolic syndrome are linked to cardiovascular dysfunction in pediatric obesity.

Introduction: Childhood obesity is associated with cardiovascular abnormalities but little is known on the potential correlation between early cardiovascular and metabolic alterations.

Aim: Aims of this study were 1) to evaluate early cardiovascular abnormalities in a large population of obese children and adolescents compared with a normal weight counterpart, 2) to investigate their potential association with insulin resistance (IR), serum uric acid (sUA) and metabolic syndrome (MetS).

Methods: This was a single-center case-control study.

GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy.

The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription.

Influence of Ultraviolet Radiation on the Association between 25-Hydroxy Vitamin D Levels and Cardiovascular Risk Factors in Obesity.

Objective: To establish if the correction with estimates of ultraviolet (UV) exposure influences the association between 25-OH-vitamin D (25OHD) levels and metabolic variables.

Study Design: A cross-sectional study was performed in 575 obese children and adolescents (>6 years of age) in a tertiary referral center. Cardiovascular risk factors were measured.

Adiponectin oligomers are similarly distributed in adequate-for-gestational-age obese children irrespective of feeding in their first year.

Background: Nutrition and growth in early postnatal life have a role in future diseases. Our aim was to investigate adiponectin oligomers in adequate-for-gestational-age obese children with respect to type and duration of feeding in the first year of life.

Methods: Adiponectin oligomers and cardiometabolic risk factors were measured in 113 adequate-for-gestational-age obese children, divided into group A (prolonged breast feeding, >6 mo), group B (short breast feeding, 1-6 mo), and group C (formula feeding from birth).

The pathophysiology of abdominal adipose tissue depots in health and disease.

Obesity is currently the most important contributor to ill health and expenditure worldwide. More alarming is the fact that the pediatric population parallels adults, with obesity closely associated to type 2 diabetes mellitus (T2D), cardiovascular disease, hypertension, non-alcoholic fatty liver disease, vitamin D deficiency (VDD) and certain types of cancer. The observation in the early 1950s that android or truncal adipose tissue (AT) distribution compared to gynoid had a greater association with metabolic dysfunction, in particular T2D and cardiovascular disease risk, led to the hypothesis that obesity-associated complications are not associated with fat mass per se, but the pattern of fat distribution.

Systematic review of ghrelin response to food intake in pediatric age, from neonates to adolescents.

Objective: Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence.

Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.

Context Objective: Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).

Pediatric obesity and vitamin D deficiency: a proteomic approach identifies multimeric adiponectin as a key link between these conditions.

Key circulating molecules that link vitamin D (VD) to pediatric obesity and its co-morbidities remain unclear. Using a proteomic approach, our objective was to identify key molecules in obese children dichotomized according to 25OH-vitamin D (25OHD) levels. A total of 42 obese children (M/F = 18/24) were divided according to their 25OHD3 levels into 25OHD3 deficient (VDD; n = 18; 25OHD<15 ng/ml) or normal subjects (NVD; n = 24; >30 ng/ml).

Super-telomeres in transformed human fibroblasts.

Telomere length maintenance is critical for organisms' long-term survival and cancer cell proliferation. Telomeres are kept within species-specific length ranges by the interplay between telomerase activity and telomeric chromatin organization. In this paper, we exploited telomerase immortalized human fibroblasts (cen3tel) that gradually underwent neoplastic transformation during culture propagation to study telomere composition and length regulation during the transformation process.

High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study.

Background: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents.

Methods: This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center.