Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays.

Background: Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified.

Methods: To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e.

VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation.

The diagnostic odysseys for rare disease patients are getting shorter as next-generation sequencing becomes more widespread. However, the complex genetic diversity and factors influencing expressivity continue to challenge accurate diagnosis, leaving more than 50% of genetic variants categorized as variants of uncertain significance.Genomic expression intricately hinges on localized interactions among its products.

Identifying metabotypes of insulin resistance severity in children with metabolic syndrome.

Background: Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity.

Safety and Effectiveness of a Biosimilar Recombinant Human Growth Hormone in Children Requiring Growth Hormone Treatment: Analysis of Final Data from PATRO Children, an International, Post-Marketing Surveillance Study.

Purpose: Omnitrope (somatropin) was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006. Here, we report final data from the PAtients TReated with Omnitrope (PATRO) Children study, a post-marketing surveillance study designed to monitor the long-term safety and effectiveness of this treatment in pediatric patients.

Methods: The study population included all pediatric patients treated with Omnitrope (biosimilar rhGH), administered via daily injection, in routine clinical practice.

Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance.

Background: Insulin resistance (IR) is considered the main driver of obesity related metabolic complications, and is related to oxidative stress and inflammation, which in turn promote each other. There is currently no specific definition of IR in children, rather, that for adult population is used by pediatric endocrinologists instead. Altered insulin secretion dynamics are associated with worse metabolic profiles and type 2 diabetes mellitus development, thus we aimed to test whether insulin response relates to oxidative stress and inflammation in children.

Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity.

Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes.

Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents with obesity and concomitant insulin resistance, who were stratified as early (N = 17, 11.

Impact of Parental Food Choices on Nutritional and Metabolic Status of Children with Type 1 Diabetes.

Parents play a key role in what their children eat. The Food Choice Questionnaire (FCQ) has been used elsewhere to assess the dietary motivations of parents of healthy children, but not for parents of children with chronic diseases such as type 1 diabetes (T1D). The aim of our research was to evaluate the associations between parental food choice motivations and the nutritional status and glycemic control of children with T1D.

Sexually dimorphic metal alterations in childhood obesity are modulated by a complex interplay between inflammation, insulin, and sex hormones.

Although growing evidence points to a pivotal role of perturbed metal homeostasis in childhood obesity, sexual dimorphisms in this association have rarely been investigated. In this study, we applied multi-elemental analysis to plasma and erythrocyte samples from an observational cohort comprising children with obesity, with and without insulin resistance, and healthy control children. Furthermore, a wide number of variables related to carbohydrate and lipid metabolism, inflammation, and sex hormones were also determined.

Trace elements as potential modulators of puberty-induced amelioration of oxidative stress and inflammation in childhood obesity.

Although puberty is known to influence obesity progression, the molecular mechanisms underlying the role of sexual maturation in obesity-related complications remains largely unexplored. Here, we delve into the impact of puberty on the most relevant pathogenic hallmarks of obesity, namely oxidative stress and inflammation, and their association with trace element blood status. To this end, we studied a well-characterized observational cohort comprising prepubertal (N = 46) and pubertal (N = 48) children with obesity.

Assessment of the perception of vertical subjectivity in children born preterm.

Children born preterm have increased rates of paediatric mortality and morbidity. Prematurity has been associated with impaired visual perception and visuo-motor integration. The alteration of the perception of verticality translates into alterations of the vestibular system at central and/or peripheral level, which may manifest itself in symptoms such as imbalance, dizziness or even vertigo.

Exploring the association between circulating trace elements, metabolic risk factors, and the adherence to a Mediterranean diet among children and adolescents with obesity.

Diet is one of the most important modifiable lifestyle factors for preventing and treating obesity. In this respect, the Mediterranean diet (MD) has proven to be a rich source of a myriad of micronutrients with positive repercussions on human health. Herein, we studied an observational cohort of children and adolescents with obesity ( = 26) to explore the association between circulating blood trace elements and the degree of MD adherence, as assessed through the KIDMED questionnaire.

Analysis and Annotation of Phospholipids by Mass Spectrometry-Based Metabolomics.

Phospholipids are essential components of membrane lipid bilayers and serve as precursors of multiple signaling molecules, so alterations in their homeostasis are associated with the pathogenesis of numerous diseases. In this context, the application of mass spectrometry-based metabolomics has demonstrated great potential to comprehensively characterize the human phospholipidome. In this chapter, we describe an untargeted method for the determination of phospholipids and other related metabolites in a variety of biological matrices, including plasma/serum, erythrocytes, and tissues, based on the combination of high-throughput direct mass spectrometry fingerprinting and subsequent profiling by ultra-high-performance reversed-phase liquid chromatography coupled to mass spectrometry.

Altered Metal Homeostasis Associates with Inflammation, Oxidative Stress, Impaired Glucose Metabolism, and Dyslipidemia in the Crosstalk between Childhood Obesity and Insulin Resistance.

Metals are redox-active substances that participate in central biological processes and may be involved in a multitude of pathogenic events. However, considering the inconsistencies reported in the literature, further research is crucial to disentangle the role of metal homeostasis in childhood obesity and comorbidities using well-characterized cohorts and state-of-the-art analytical methods. To this end, we studied an observational population comprising children with obesity and insulin resistance, children with obesity without insulin resistance, and healthy control children.

Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes.

Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes.

Characterization of the Plasmatic and Erythroid Multielemental Biodistribution in Childhood Obesity Using a High-Throughput Method for Size Fractionation of Metal Species.

In this chapter, we describe a metallomics method based on protein precipitation under non-denaturing conditions and further analysis by inductively coupled plasma mass spectrometry for high-throughput metal speciation in plasma and erythrocyte samples. This methodology enables to study the total multielemental profile of these biological matrices, as well as to quantify the metal fractions conforming the metallometabolome and the metalloproteome. Furthermore, the analytical coverage comprises several essential and toxic metal elements, namely aluminum, arsenic, cadmium, cobalt, chromium, copper, iron, lithium, manganese, molybdenum, nickel, lead, selenium, vanadium, and zinc.

Untargeted Metabolomics Based on Liquid Chromatography-Mass Spectrometry for the Analysis of Plasma and Erythrocyte Samples in Childhood Obesity.

The circulating metabolome of human peripheral blood provides valuable information to investigate the molecular mechanisms underlying the development of diseases and to discover candidate biomarkers. In particular, erythrocytes have been proposed as potential systemic indicators of the metabolic and redox status of the organism. To accomplish wide-coverage metabolomics analysis, the combination of complementary analytical techniques is necessary to manage the physicochemical complexity of the human metabolome.

Catalase post-translational modifications as key targets in the control of erythrocyte redox homeostasis in children with obesity and insulin resistance.

Insulin resistance (IR) is the most common metabolic disturbance in children with obesity. Children with obesity and insulin resistance (ObIR+) display a detriment in erythroid antioxidant defenses, caused by an impaired catalase activity and the increase in oxidative and pro-inflammatory markers. Therefore, erythrocytes from ObRI+ are more vulnerable to any oxidative stress elicitor.

Test-retest of the Subjective Visual Vertical Test performed using a mobile application with the smartphone anchored to a turntable.

Purpose: The alterations of the Subjective visual vertical test are related to vestibular pathology. Our previously validated method to distinguish between healthy and pathological individuals measures the deviation from the Subjective visual vertical using a mobile application installed on a smartphone fixed to a turntable anchored to the wall. The aim of this study was evaluating the intra-observer reliability of our method in individuals with or without vestibular pathology.

Adherence to Mediterranean Diet Is Associated With Better Glycemic Control in Children With Type 1 Diabetes: A Cross-Sectional Study.

Unlabelled: Type 1 diabetes (T1D) is a chronic condition, with increased morbidity and mortality, due to a higher rate of cardiovascular disease among other factors. Cardiovascular risk increases with the worse glycemic profile. Nutrition has a deep impact on diabetes control.

Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF-1 levels, while improving height in patients small for gestational age A long-term observational study.

Objective: In children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance (IR) has only been investigated for a short period, necessitating a longer observation period. This study aimed to evaluate the long-term (10 years) effect of GH to SGA-children on IR and safety during treatment.

Design: This was a multicenter observational study.

Levels of lactic acid's concordance with pH in pediatric parapneumonic pleural effusion.

Unlabelled: Purpose of the article: The indication of pleural drainage in parapneumonic pleural effusion (PPE) is still controversial. Pleural fluid's (PF) pH is widely used as an indicator of the need for pleural drainage. We hypothesized that PF's lactate will have a high concordance with pH, and thus, may be a valuable tool to determine the need for pleural drainage in pediatric PPE.

Efficacy of the subjective visual vertical test performed using a mobile application to detect vestibular pathology.

Background: The subjective visual vertical (SVV) test is a sensitive test of vestibular dysfunction that allows the evaluation of otolithic organs; however, with the current method, there are technical and logistical limitations that make the application of this test difficult in the conventional clinic.

Objective: The objective of this study is to assess the effectiveness of detecting vestibular pathology using the SVV via a new screening method.

Methods: A consecutive sample of 62 patients with suspected vestibular pathology was included in the study.

Hybrid Closed-Loop System Achieves Optimal Perioperative Glycemia in a Boy With Type 1 Diabetes: A Case Report.

The goal in type 1 diabetes (T1D) therapy is to maintain optimal glycemic control under any circumstance. Diabetes technology is in continuous development to achieve this goal. The most advanced Food and Drug Administration- and European Medicines Agency-approved devices are hybrid closed-loop (HCL) systems, which deliver insulin subcutaneously in response to glucose levels according to an automated algorithm.

Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line.

Basic research on types 1 and 2 diabetes mellitus require early stage studies using beta cells or cell lines, ideally of human origin and with preserved insulin secretion in response to glucose. The 1.1E7 cells are a hybrid cell line resulting from the electrofusion of dispersed human islets and PANC-1 cells, capable of secreting insulin in response to glucose, but their survival and function under toxic conditions remains untested.

Mechanistic Insights into Alzheimer's Disease Unveiled through the Investigation of Disturbances in Central Metabolites and Metabolic Pathways.

Hydrophilic metabolites are closely involved in multiple primary metabolic pathways and, consequently, play an essential role in the onset and progression of multifactorial human disorders, such as Alzheimer's disease. This review article provides a comprehensive revision of the literature published on the use of mass spectrometry-based metabolomics platforms for approaching the central metabolome in Alzheimer's disease research, including direct mass spectrometry, gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Overall, mounting evidence points to profound disturbances that affect a multitude of central metabolic pathways, such as the energy-related metabolism, the urea cycle, the homeostasis of amino acids, fatty acids and nucleotides, neurotransmission, and others.