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.

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.

Cost-Utility Analysis of Adjuvant Olaparib for Germline BRCA1/2-Mutated, High-Risk HER2-Negative Early Breast Cancer in Spain.

Objective: Here we estimate the cost-effectiveness of olaparib in the Spanish National Health Service (SNHS) as adjuvant treatment of early germline mutations in the BRCA1/2 genes (gBRCAm) HER2-negative (HER2neg) breast cancer (BC) with high risk of recurrence.

Methods: A semi-Markov model was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a lifetime horizon. Two scenarios were compared: receiving olaparib versus standard of care (SoC) treatment.

Association between childhood obesity, trace elements, and heavy metals: Recent discoveries and future perspectives.

Trace elements and heavy metals play pivotal roles in health status by regulating a myriad of vital biological functions. Abnormal metal homeostasis has been linked to a constellation of pathogenic complications, including oxidative stress, inflammatory processes, dyslipidemia, and impaired insulin-mediated metabolism of carbohydrates, thereby increasing the odds of developing childhood obesity and related comorbidities. Herein, we provide a comprehensive revision of recent literature on the association between childhood obesity, trace elements, and heavy metals.

Aortic thrombosis and acute kidney injury due to atherosclerosis in a dog.

Objective: Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Due to its cardiovascular ischemic complications, it is one of the most common causes of death in people. However, atherosclerosis is seldomly reported in dogs.

Somatostatin: a possible mediator of the long-term effects of experimental vertical gastrectomy on glucose metabolism in rats?

Background: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric surgeries. SG treats type 2 diabetes mellitus better than several drugs. The mechanisms that underlie this phenomenon are not clear.

Mass Spectrometry-Based Metabolomics Multi-platform for Alzheimer's Disease Research.

The integration of complementary analytical platforms is nowadays the most common strategy for comprehensive metabolomics analysis of complex biological systems. In this chapter, we describe methods and tips for the application of a mass spectrometry multi-platform in Alzheimer's disease research, based on the combination of direct mass spectrometry and orthogonal hyphenated approaches, namely, reversed-phase ultrahigh-performance liquid chromatography and gas chromatography. These procedures have been optimized for the analysis of multiple biological samples from human patients and transgenic animal models, including blood serum, various brain regions (e.

Parental obesity predisposes to exacerbated metabolic and inflammatory disturbances in childhood obesity within the framework of an altered profile of trace elements.

Background: Family history of obesity is known to increase the odds of developing childhood obesity in the offspring, but its influence in underlying molecular complications remains unexplored.

Subjects/methods: Here, we investigated a population-based cohort comprising children with obesity, with and without parental obesity (PO+, N = 20; PO-, N = 29), and lean healthy children as controls (N = 30), from whom plasma and erythrocyte samples were collected to characterize their multi-elemental profile, inflammatory status, as well as carbohydrate and lipid metabolisms.

Results: We found parental obesity to be associated with unhealthier outcomes in children, as reflected in increased blood insulin levels and reduced insulin sensitivity, unfavorable lipid profile, and pro-inflammatory milieu.

Economic impact of the use of patiromer in chronic kidney disease or heart failure for the treatment of chronic hyperkalemia in Spain.

Introduction: Chronic hyperkalemia has negative consequences in the medium and long term, and determines the suspension of nephro and cardioprotective drugs, such as renin-angiotensin-aldosterone system inhibitors (RAASi). There is an alternative to the suspension or dose reduction of these treatments: the administration of potassium chelators. The aim of this study is to estimate the economic impact of the use of patiromer in patients with chronic kidney disease (CKD) or heart failure (HF) and hyperkalemia in Spain.

QC: Recommendations and Guidelines for Robust, Easily Implementable and Reportable Quality Control of Metabolomics Data.

The implementation of quality control strategies is crucial to ensure the reproducibility, accuracy, and meaningfulness of metabolomics data. However, this pivotal step is often overlooked within the metabolomics workflow and frequently relies on the use of nonstandardized and poorly reported protocols. To address current limitations in this respect, we have developed QC, a robust, easily implementable and reportable method for monitoring and controlling data quality.

Retrospective evaluation of hematological ratios in canine parvovirosis: 401 cases.

Background: The utility of neutrophil-to-lymphocyte ratio (NLR), platelet to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) as prognostic indicators has not been investigated in canine parvovirosis (CPV).

Hypothesis: To evaluate whether these hematological ratios obtained at hospital admission in CPV are associated with outcome or duration of hospitalization.

Animals: Four hundred one client-owned dogs presented with CPV.

How far are we from reliable metabolomics-based biomarkers? The often-overlooked importance of addressing inter-individual variability factors.

Metabolomics has proven great potential to unravel the molecular basis of diseases. However, most attempts aimed at identifying reliable metabolomics-based biomarkers for diagnosis, prediction, and prognosis of diseases have repeatedly failed because of inconsistent results and unsatisfactory replication in independent cohorts. This review article explores the possible causes behind this reproducibility crisis, with special focus on the role that inter-individual variability factors play in modulating the susceptibility to disease development.

Childhood obesity, metabolic syndrome, and oxidative stress: microRNAs go on stage.

The incidence of childhood obesity and metabolic syndrome has grown notably in the last years, becoming major public health burdens in developed countries. Nowadays, oxidative stress is well-recognized to be closely associated with the onset and progression of several obesity-related complications within the framework of a complex crosstalk involving other intertwined pathogenic events, such as inflammation, insulin disturbances, and dyslipidemia. Thus, understanding the molecular basis behind these oxidative dysregulations could provide new approaches for the diagnosis, prevention, and treatment of childhood obesity and associated disorders.

The role of glucagon after bariatric/metabolic surgery: much more than an "anti-insulin" hormone.

The biological activity of glucagon has recently been proposed to both stimulate hepatic glucose production and also include a paradoxical insulinotropic effect, which could suggest a new role of glucagon in the pathophysiology type 2 diabetes mellitus (T2DM). An insulinotropic role of glucagon has been observed after bariatric/metabolic surgery that is mediated through the GLP-1 receptor on pancreatic beta cells. This effect appears to be modulated by other members of the proglucagon family, playing a key role in the beneficial effects and complications of bariatric/metabolic surgery.

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.

Cost-effectiveness of the CNIC-Polypill versus separate monocomponents in cardiovascular secondary prevention in Spain.

Introduction And Objectives: Despite advances in treatment, cardiovascular disease is the second leading cause of death in Spain. The objective of this study was to determine the cost-effectiveness of the CNIC-Polypill strategy (acetylsalicylic acid 100 mg, atorvastatin 20/40 mg, ramipril 2.5/5/10 mg) compared with the same separate monocomponents for the secondary prevention of recurrent cardiovascular events in adults in Spain.

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.

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.

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.

Cost-benefit analysis of ALK diagnosis vs. non-diagnosis in patients with advanced non-small cell lung cancer in Spain.

Introduction: In recent years, target therapies to specific molecular alterations in advanced non-small cell lung cancer (NSCLC) have been identified and have shown superior efficacy compared to non-targeted treatments. Anaplastic lymphoma kinase (ALK) is one of the therapeutic targets; nevertheless, ALK diagnosis is not performed in all NSCLC patients in Spain. The objective of this study is to estimate in monetary terms the benefit for the Spanish society of ALK diagnosis in advanced NSCLC patients.

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.