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. A cross-sectional observational study of children aged 5 to 16 years with T1D attending the Pediatric Endocrinology Unit of Puerta del Mar University Hospital in Cádiz (Spain) was performed. Demographic, anthropometric and clinical data, including glycated hemoglobin, were collected. The FCQ in Spanish was conducted to assess the eating behaviors of the main caregivers of children with T1D. Significance was established at the level of p-value < 0.05. In total, 85 children with T1D (female 56.5%, age 12.07 ± 2.93 years, HbA1c 7.29 ± 0.77%) were recruited. Of these children, 31.3% showed HbA1c levels of <7.0% and 44.9% had a TIR >70%. A significant positive correlation was found between Hb1Ac and "familiarity" (R: +0.233). Anthropometric measures (weight, BMI, skinfolds and body circumferences) showed significant positive correlations with "sensory appeal" and "price". Parents' eating behaviors influence the nutritional status of their children with T1D and their glycemic control of the disease.

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, 11.4 ± 2.4 years), middle (N = 16, 11.8 ± 1.9 years), and late (N = 33, 11.7 ± 2.0 years) responders according to the insulin secretion profile in response to an oral glucose tolerance test. To this end, we employed a high-throughput method aimed at determining the biodistribution of various essential and toxic elements by analyzing total metal contents, metal-containing proteins, and labile metal species. RESULTS: Compared with the early responders, participants with delayed glucose-induced hyperinsulinemia showed a worsened insulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL; LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances in the levels of plasmatic proteins containing chromium (4.8 vs. 5.1 µg/L), cobalt (0.79 vs. 1.2 µg/L), lead (0.021 vs. 0.025 µg/L), and arsenic (0.077 vs. 0.17 µg/L). A correlation analysis demonstrated a close inter-relationship among these multielemental perturbations and the characteristic metabolic complications occurring in childhood obesity, namely impaired insulin-mediated metabolism of carbohydrates and lipids. CONCLUSIONS: These findings highlight the crucial involvement that altered metal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, and dyslipidemia in childhood obesity.

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. From all participants, plasma and erythrocyte samples were collected and subjected to metallomics analysis and determination of classical biomarkers of oxidative stress and inflammation. Besides the expected raise of sexual hormones, pubertal children displayed better inflammatory and oxidative control, as reflected by lower levels of C-reactive protein and oxidative damage markers, as well as improved antioxidant defense. This was in turn accompanied by a healthier multielemental profile, with increased levels of essential elements involved in the antioxidant system and metabolic control (metalloproteins containing zinc, molybdenum, selenium, and manganese) and decreased content of potentially deleterious species (total copper, labile free iron). Therefore, our findings suggest that children with obesity have an exacerbated inflammatory and oxidative damage at early ages, which could be ameliorated during pubertal development by the action of trace element-mediated buffering mechanisms.

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. Children with obesity, regardless of sex and insulin resistance status, showed increased plasma copper-to-zinc ratios. More interestingly, obesity-related erythroid alterations were found to be sex-dependent, with increased contents of iron, zinc, and copper being exclusively detected among female subjects. Our findings suggest that a sexually dimorphic hormonal dysregulation in response to a pathological cascade involving inflammatory processes and hyperinsulinemia could be the main trigger of this female-specific intracellular sequestration of trace elements. Therefore, the present study highlights the relevance of genotypic sex as a susceptibility factor influencing the pathogenic events behind childhood obesity, thereby opening the door to develop sex-personalized approaches in the context of precision medicine.

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. Furthermore, we also review the characteristic fragmentation patterns of phospholipids with the aim of providing simple guidelines for their straightforward annotation.

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. Herein, we describe an untargeted metabolomics method to capture the plasmatic and erythroid metabolomes based on ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry, combining reversed-phase liquid chromatography and hydrophilic interaction liquid chromatography. The method provides comprehensive metabolomics fingerprinting of plasma and erythrocyte samples, thereby enabling the elucidation of the distinctive metabolic disturbances behind childhood obesity and associated comorbidities, such as insulin resistance.

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. Altogether, the metallomics method here proposed represents an excellent approach to comprehensively characterize the metal biodistribution in human peripheral blood, which would enable to decipher the role of metal homeostasis in health and disease, and particularly in childhood obesity.

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. A multi-elemental approach based on the size-fractionation of metal species was applied to quantify the total content of various essential and toxic elements in plasma and erythrocyte samples, and to simultaneously investigate the metal fractions conforming the metalloproteome and the labile metal pool. The most important disturbances in childhood obesity were found to be related to elevated circulating copper levels, decreased content of plasmatic proteins containing chromium, cobalt, iron, manganese, molybdenum, selenium, and zinc, as well as the sequestration of copper, iron, and selenium within erythrocytes. Interestingly, these metal disturbances were normally exacerbated among children with concomitant insulin resistance, and in turn were associated to other characteristic pathogenic events, such as inflammation, oxidative stress, abnormal glucose metabolism, and dyslipidemia. Therefore, this study represents one-step further towards a better understanding of the involvement of metals in the crosstalk between childhood obesity and insulin resistance.

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. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.

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 (N = 26) to explore the association between circulating blood trace elements and the degree of MD adherence, as assessed through the KIDMED questionnaire. Participants with higher MD adherence showed better glycemic/insulinemic control and a healthier lipid profile, as well as raised plasma levels of selenium, zinc, cobalt, molybdenum, and arsenic, and increased erythroid content of selenium. Interestingly, we found that these MD-related mineral alterations were closely correlated with the characteristic metabolic complications behind childhood obesity, namely hyperglycemia, hyperinsulinemia, and dyslipidemia (p < 0.05, |r| > 0.35). These findings highlight the pivotal role that dietary trace elements may play in the pathogenesis of obesity and related disorders.

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

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. MATERIALS AND METHODS: We performed a descriptive, prospective study sequentially enrolling those pediatric patients admitted to a tertiary University Hospital with a PPE between 2008 and 2018. Patients were classified in two groups: drainable PPE (pH < 7) and non-drainable PPE (pH > 7). Correlation with the pH, the area under the curve (AUC), and the sensitivity and specificity values for lactate and other parameters (glucose, and LDH) were analysed too. RESULTS: 72 patients with a median age of 4 years (interquartile range 2.25-6) were included. Both groups were homogeneous. Lactate levels were higher in the drainable PPE group (p < 0.001), and a strong inverse correlation between pH and lactate was found (r: -0.7; p < 0.001). A lactate cut-off value of 60.5 mmol/L, exhibit an AUC of 0.86 with a sensitivity of 70% and a high specificity (97.9%) to predict a pH < 7. CONCLUSIONS: Our data indicates that lactate in PF presents a strong correlation with pH and could potentially serve as a highly specific biomarker of the need for pleural drainage.

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.

Lung ultrasound score and diuretics in preterm infants born before 32 weeks: A pilot study.

OBJECTIVE: To describe if weekly determined lung ultrasound (LU) scores in preterm infants born before 32 weeks (PTB32W) change with diuretic therapy. DESIGN: We included infants who received diuretics and compared LU scores according to their evolution on respiratory support (RS) before and after diuretics. RESULTS: We included 18 PTB32W divided into two groups. Both groups were similar in terms of median gestational age: 26 weeks (interquartile range [IQR]: 25-28) in the responders' group and 27 weeks (IQR: 24-28) in the other. They differed, however, in the median number of days on invasive mechanical ventilation: 27 (IQR: 11-43) versus 76 (IQR: 35-117), p = .03; in addition to the number of infants with moderate-severe bronchopulmonary dysplasia: 3 (33%) versus 8 (89%), p = .025. The responders' group showed lower LU scores 2 days after diuretics, with a median LU score of 6 (IQR: 3-12) versus 14 (IQR: 12-17) in the nonresponders group, p = .03; 1 week after (3 [IQR: 0-10] versus 12 [12-12], p = .04); and 3 weeks after (5 [IQR: 3-6] versus 12 [10-15], p = .01). RS also decreased at the same time: 7 out of 9 (78%) were extubated in the responders' group, and 1 out of 9 (11%) in the nonresponders group, p = .02, and these differences remained throughout the entire follow-up. CONCLUSIONS: There is a group of PTB32W patients whose LU score improves after diuretics. This change appears only in those patients that can be weaned off from RS, and at the same period of time as the administration of diuretics.

Iron Metabolism in Obesity and Metabolic Syndrome.

Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.

Pleural line thickness reference values for preterm and term newborns.

BACKGROUND: In lung ultrasound (LUS), the pleural line is an artifact whose thickness depends on the underlying lung pathology. To date there are no published studies on normal values of pleural line thickness (PLT) in newborns. OBJECTIVE: The aim of our study is to describe normal PLT values in term newborn (TN) and preterm newborn (PTN). METHODS: We recruited eupneic TN and PTN, under 34 weeks of gestation, on their first 24 hours of life. Newborns presenting any respiratory distress since birth were excluded. LUS was performed in four areas: upper anterior, lower anterior, lateral and posterior. At each location, we measured PLT and values where compared. Intraobserver and interobserver agreement were assessed using the intraclass correlation coefficient (ICC), and the kappa coefficient. RESULTS: We included 23 TN with a median birth weight of 3365 g (interquartile range [IQR] 3100-3575 g) and a median gestational age of 39 weeks (IQR, 38-40 weeks). In the PTN group, 23 patients were included with a median birth weight of 1350 g (IQR, 1150-1590 g) and a median gestational age of 31 weeks (IQR, 30-32 weeks). Median PLT values were less than 1 mm, and there were no significant differences between groups at any locations, with the exception of the left lower anterior field (0.79 mm [IQR, 0.72-0.89 mm] vs 0.68 mm [IQR, 0.62-0.72 mm]). Intraobserver agreement was high: consistency ICC 0.77 (95% confidence interval [CI], 0.32-0.92) and absolute ICC 0.78 (95% CI, 0.34-0.93). Interobserver agreement was high for the definition of thin pleural line as less than 1 mm. CONCLUSIONS: TN and asymptomatic PTN have similar PLT values. Overall, PLT in healthy newborns should be less than 1 mm.

NT-proBNP plasma levels as biomarkers for pulmonary hypertension in healthy infants with respiratory syncytial virus infection.

Aim: To explore NT-proBNP as biomarker for pulmonary hypertension (PH) in infants with respiratory syncytial virus infection (RSVI). Patients & methods: We prospectively enrolled 93 healthy infants with RSVI aged 1-12 months. NT-proBNP determination and echocardiography were performed at admission. Results: PH was found in 22% of patients and associated with a severe course of the disease. NT-proBNP >1635 pg/ml resulted an independent predictor for PH (odds ratio: 16.46 [95% CI: 4.10-66; p < 0.001]). The diagnostic performance of NT-proBNP to detect PH in RSVI was high (area under receiver operator curve of 0.932 [95% CI: 0.883-0.981; p < 0.001]). Conclusions: The presence of PH in healthy infants with RSVI is associated with worse outcomes. NT-proBNP resulted an accurate biomarker for PH in this setting.

High-Throughput Metabolomics Based on Direct Mass Spectrometry Analysis in Biomedical Research.

Metabolomics based on direct mass spectrometry analysis shows a great potential in biomedical research because of its high-throughput screening capability and wide metabolome coverage. This chapter contains detailed protocols to perform comprehensive metabolomic fingerprinting of multiple biological samples (serum, plasma, urine, brain, liver, spleen, thymus) by using complementary analytical platforms. The most important issues to be considered are discussed, including sample treatment, metabolomic analysis, raw data preprocessing, and data analysis.

Broad spectrum antibiotics in newborns increase multi-drug resistant infections.

Our objective was to determine if broad spectrum antibiotics (BSA) are associated with multi-resistant bacterial (MRB) infections in neonatal patients. We conducted a case-control study with two groups of patients: those with and without a MRB infection. We included 43 cases and 43 controls. MRB strains were: 21 S. maltophila (49%), 11 ESBL-producing Enterobacteriae (25%), 8 P. aeruginosa (19%) and 3 MRSA (7%). Odds ratio (OR) for MRB after seven days of carbapenems was 4.25 (95% confidence interval (CI) 1.4-17.4) and OR for MRB after seven days of third generation cephalosporin was 8 (95% CI 1.1-34.9). BSA longer than seven days, increases MRB infections 22.5 times in patients with bronchopulmonary dysplasia (BPD). Our data show a clear association between the use of BSA and the development of MRB infections, especially in BPD. Although we cannot state this is a causal relationship, we can recommend avoiding prolonged treatment with these antibiotics in preterm babies at risk of BPD.

Intervention and Observational Trials are Complementary in Metabolomics: Diabetes and the Oral Glucose Tolerance Test.

Observational experimental designs are usually employed in metabolomics to elucidate pathological mechanisms underlying disease development and to discover candidate biomarkers for diagnosis. However, intervention trials can also be a suitable starting point before performing a validation study in lager epidemiological cohorts, with a great potential in personalized medicine to investigate how different patients respond to similar stimuli. In the present work, we provide a review of the literature on the application of metabolomics to investigate metabolic alterations associated with diabetes, the diabetes predisposing state of insulin resistance and the oral glucose tolerance test as a case study to demonstrate the complementarity of observational and interventional study designs.

An Overview on the Importance of Combining Complementary Analytical Platforms in Metabolomic Research.

The analytical bias introduced by most of the commonly used techniques in metabolomics considerably hinders the simultaneous detection of all metabolites present in complex biological samples. In order to solve this limitation, the combination of complementary approaches is emerging in recent years as the most suitable strategy in order to maximize metabolite coverage. This review article presents a general overview of the most important analytical techniques usually employed in metabolomics: nuclear magnetic resonance, mass spectrometry and hybrid approaches. Furthermore, we emphasize the potential of integrating various tools in the form of metabolomic multi-platforms in order to get a deeper metabolome characterization, for which a revision of the existing literature in this field is provided. This review is not intended to be exhaustive but, rather, to give a practical and concise guide to readers not familiar with analytical chemistry on the considerations to account for the proper selection of the technique to be used in a metabolomic experiment in biomedical research.