Adherence to a healthy lifestyle behavior composite score and cardiometabolic risk factors in Spanish children from the CORALS cohort.

To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors.   Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

Reproducibility and relative validity of a semi-quantitative food and beverage frequency questionnaire for Spanish children aged 3 to 11 years: the COME-Kids F&B-FQ.

A reliable food and beverage frequency questionnaire (F&B-FQ) to measure dietary intakes for children across Spain is currently unavailable. Thus, we designed and assessed the reproducibility and relative validity of a new F&B-FQ in 210 Spanish children aged 3-11 years. COME-Kids F&B-FQ contained 125 items to assess the usual diet intake in the past year among children. To explore the reproducibility, caregivers answered COME-Kids F&B-FQ twice over a 15-day period (± 1 week). To evaluate the relative validity, estimates from a third COME-Kids F&B-FQ administered at 1 year of follow-up were compared with the mean estimates from 3-day dietary records (3d-DR) collected at baseline, 6 months, and after 1 year of follow-up. Reproducibility and relative validity of the COME-Kids F&B-FQ in estimating food groups and nutrients were assessed using Pearson (r) and intra-class (ICC) correlation coefficients. We used the kappa index to evaluate the agreement in repeat administrations or with the 3d-DR. We used Bland-Altman plots to identify bias across levels of intake. A total of 195 children (105 boys, 90 girls) completed the study. The reproducibility of data estimated from COME-Kids F&B-FQ was substantial with mean r and ICC being 0.65 and 0.64 for food groups and 0.63 and 0.62 for nutrients, respectively. Validation assessments comparing the FFQ and 3d-DRs showed r = 0.36 and ICC = 0.30 for food groups and r = 0.29 and ICC = 0.24 for nutrients. The mean agreement for food group reproducibility and relative validity was 86% and 65%, respectively. These estimates were 85% for reproducibility and 64% for relative validity in the case of nutrients. For reproducibility and relative validity, the overall mean kappa index was 63% and 37% for all food groups and 52% and 27% for nutrients, respectively. Bland-Altman plots showed no specific bias relating to the level of intake of nutrients and several food groups. CONCLUSION: COME-Kids F&B-FQ showed substantial reproducibility and acceptable relative validity to assess food and beverage intake in Spanish children aged 3 to 11 years. Most children were correctly classified in relation to the intake of food groups and nutrients, and misclassification was unlikely with reference to 3d-DR. WHAT IS KNOWN: • The estimation of dietary intake in children is complex, especially in large cohorts. • The food frequency questionnaire is a well-recognized and the most frequently used method for assessing food consumption. WHAT IS NEW: • A new food and beverage frequency questionnaire including a beverage section and novel plant-based food items has been validated in Spanish children aged 3-11 years.

Circadian Disruption and Mental Health: The Chronotherapeutic Potential of Microbiome-Based and Dietary Strategies.

Mental illness is alarmingly on the rise, and circadian disruptions linked to a modern lifestyle may largely explain this trend. Impaired circadian rhythms are associated with mental disorders. The evening chronotype, which is linked to circadian misalignment, is a risk factor for severe psychiatric symptoms and psychiatric metabolic comorbidities. Resynchronization of circadian rhythms commonly improves psychiatric symptoms. Furthermore, evidence indicates that preventing circadian misalignment may help reduce the risk of psychiatric disorders and the impact of neuro-immuno-metabolic disturbances in psychiatry. The gut microbiota exhibits diurnal rhythmicity, as largely governed by meal timing, which regulates the host's circadian rhythms. Temporal circadian regulation of feeding has emerged as a promising chronotherapeutic strategy to prevent and/or help with the treatment of mental illnesses, largely through the modulation of gut microbiota. Here, we provide an overview of the link between circadian disruption and mental illness. We summarize the connection between gut microbiota and circadian rhythms, supporting the idea that gut microbiota modulation may aid in preventing circadian misalignment and in the resynchronization of disrupted circadian rhythms. We describe diurnal microbiome rhythmicity and its related factors, highlighting the role of meal timing. Lastly, we emphasize the necessity and rationale for further research to develop effective and safe microbiome and dietary strategies based on chrononutrition to combat mental illness.

Reduced Free Fatty Acid Receptor 4 Gene Expression is Associated With Extreme Obesity and Insulin Resistance in Children.

OBJECTIVES: Free fatty acid receptor 4 (FFAR4) is a G-protein-coupled membrane receptor highly expressed in macrophages that triggers anti-inflammatory effects and promotes insulin sensitization. We have previously found significant associations between the FFAR4 rs11187533 single nucleotide polymorphism (SNP) and various obesity comorbidity parameters. We aimed to verify the FFAR4 expression levels in children with obesity and the associated comorbidities. METHODS: Thirty-eight children with obesity were studied. Clinical and anthropometric evaluation was performed. A venous sample under fasting conditions was obtained. Biochemical study included parameters of metabolic risk. DNA was extracted and genotyped for the rs11187533 FFAR4 SNP. Real-time PCR technique was performed to investigate the gene expression. Relative FFAR4 mRNA levels were determined according to the 2-ΔΔCt method. RESULTS: Significant differences in FFAR4 expression levels between the CC and CT-TT genotypes of the rs11187533 FFAR4 SNP were observed (P = 0.034). The minor allele T presented higher levels of FFAR4 expression. We found that a loss of FFAR4 expression was associated with extreme obesity (P = 0.032). The lowest FFAR4 expression levels were observed in children who had higher insulin (P = 0.008) and homeostasis model assessment insulin resistance values (P = 0.012) and lower quantitative insulin-sensitivity check index (P = 0.033). CONCLUSIONS: The underexpression of FFAR4 was associated with extreme obesity and parameters indicative of obesity comorbidities in children. This under expression could be partially influenced by the presence of the C allele rs11187533 FFAR4 SNP.

Correlation of Anti-Tissue Transglutaminase Antibodies With the Mucosal Changes and IgA Status of Children With Celiac Disease.

OBJECTIVES: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD). METHODS: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed. RESULTS: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms. CONCLUSIONS: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels.

Spanish National Registry of Paediatric Coeliac Disease: Changes in the Clinical Presentation in the 21st Century.

OBJECTIVES: Over the last several decades, there has been a tendency towards a predominance of less symptomatic forms of coeliac disease (CD) and an increase in the patient age at diagnosis. This study aimed to assess the clinical presentation and diagnostic process of paediatric CD in Spain. METHODS: A nationwide prospective, observational, multicentre registry of new paediatric CD cases was conducted from January 2011 to June 2017. The data regarding demographic variables, type of birth, breast-feeding history, family history of CD, symptoms, height and weight, associated conditions, serological markers, human leukocyte antigen (HLA) phenotype, and histopathological findings were collected. RESULTS: In total, 4838 cases (61% girls) from 73 centres were registered. The median age at diagnosis was 4 years. Gastrointestinal symptoms were detected in 71.4% of the patients, and diarrhoea was the most frequent symptom (45.9%). The most common clinical presentation was the classical form (65.1%) whereas 9.8% ofthe patients were asymptomatic. There was a trend towards an increase in the age at diagnosis, proportion of asymptomatic CD cases, and usage of anti-deamidated gliadin peptide antibodies and HLA typing for CD diagnosis. There was, however, a decreasing trend in the proportion of patients undergoing biopsies. Some of these significant trend changes may reflect the effects of the 2012 ESPGHAN diagnosis guidelines. CONCLUSIONS: Paediatric CD in Spain is evolving in the same direction as in the rest of Europe, although classical CD remains the most common presentation form, and the age at diagnosis remains relatively low.

Melatonin in Early Nutrition: Long-Term Effects on Cardiovascular System.

Breastfeeding protects against adverse cardiovascular outcomes in the long term. Melatonin is an active molecule that is present in the breast milk produced at night beginning in the first stages of lactation. This indoleamine appears to be a relevant contributor to the benefits of breast milk because it can affect infant health in several ways. The melatonin concentration in breast milk varies in a circadian pattern, making breast milk a chrononutrient. The consumption of melatonin can induce the first circadian stimulation in the infant's body at an age when his/her own circadian machinery is not functioning yet. This molecule is also a powerful antioxidant with the ability to act on infant cells directly as a scavenger and indirectly by lowering oxidant molecule production and enhancing the antioxidant capacity of the body. Melatonin also participates in regulating inflammation. Furthermore, melatonin can participate in shaping the gut microbiota composition, richness, and variation over time, also modulating which molecules are absorbed by the host. In all these ways, melatonin from breast milk influences weight gain in infants, limiting the development of obesity and comorbidities in the long term, and it can help shape the ideal cellular environment for the development of the infant's cardiovascular system.

Leukocyte-Endothelium Interaction Is Associated with Fat Mass in Children.

OBJECTIVE: To study leukocyte-endothelium interaction, a measure of the initial phase of atheromatosis, in children with overweight or obesity. STUDY DESIGN: A prospective study was conducted in 77 children aged 7-16 years; 47 were children with overweight/obesity and 30 were normal weight. Polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells were isolated from venous blood samples and the interaction of leukocytes over a monolayer of human umbilical vein endothelial cells was analyzed using flow chamber microscopy. The variables studied included leukocyte rolling velocity, rolling flux, and adhesion to endothelial cells. These were compared between children with overweight/obesity and control children. Correlation between the measures of leukocyte-endothelium interaction and anthropometric and biochemical variables was evaluated. RESULTS: In comparison with normal weight children, the PMNs and peripheral blood mononuclear cells of the overweight/obesity group showed a reduction in rolling velocity (P = .000 and P = .001, respectively) and an increase in rolling flux (P = .001 and P = .004), and adhesion (P = .003 and P = .002). The homeostasis model of insulin resistance was correlated inversely with rolling velocity and positively with rolling flux in PMNs. C-reactive protein was correlated positively with rolling flux and adhesion in both types of leucocytes. Fat mass index was correlated with all measures of leukocyte-endothelial interaction and proved to be the main predictor of leukocyte adhesion in the multiple regression analysis (P = .001 for PMNs and P = .006 for peripheral blood mononuclear cells). CONCLUSIONS: Excess fat mass in children is related to the activation of the leukocyte-endothelium interaction, potentially contributing to the development of atherosclerosis.

The rs11187533 C>T Variant of the FFAR4 Gene Is Associated with Lower Levels of Fasting Glucose and Decreases in Markers of Liver Injury in Children with Obesity.

INTRODUCTION: Genetic factors can modulate the development of associated comorbidities in obesity. It has been shown that loss-of-function variants of the free fatty acid receptor 4 (FFAR4) gene negatively affect obesity comorbidities such as insulin resistance and fatty liver disease. OBJECTIVE: To test the relationships of metabolic factors in children with obesity with variants of the FFAR4 gene. METHODS: We performed an association study of 3 single nucleotide polymorphisms (SNPs) of FFAR4 (rs10882273 T>C, rs12243124 T>C, and rs11187533 C>T) covering the last intron and last exon of FFAR4 in a cohort of 203 children with obesity. Cardiometabolic factors were determined, including parameters related to insulin resistance, liver injury, and high-sensitivity C-reactive protein as an inflammatory marker. RESULTS: Significant genotype - phenotype interactions occurred between the rs11187533 SNP and glucose levels (p = 0.011). Moreover, we identified 2 marginally significant associations between this SNP and the hepatic enzymes alanine aminotransferase (p = 0.022) and gamma-glutamyltransferase (p = 0.015). The homozygous minor allele genotype (TT) was associated with a decrease in glucose levels. CONCLUSION: The homozygous minor allele genotype of the rs11187533 SNP might be protective against metabolic consequences accompanying obesity and could allow the identification of metabolically healthy obese individuals at early ages.

Molecular aspects of pancreatic ß-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA.

Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic ß-cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic ß-cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the ß cell via activation or inhibition of several processes and targets, such as receptor-signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic ß-cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic ß-cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic ß-cell dysfunction.

Bifidobacterium pseudocatenulatum CECT 7765 supplementation improves inflammatory status in insulin-resistant obese children.

PURPOSE: The relationships between gut microbiota and obesity-related co-morbidities have been increasingly recognized. Low-grade inflammation may be the main factor in the pathogenesis of such disorders. We investigated the effect of the potential probiotic Bifidobacterium pseudocatenulatum CECT 7765 on cardiometabolic risk factors, inflammatory cytokines and gut microbiota composition in obese children with insulin resistance. METHODS: The study included 48 obese children (10-15 years old) with insulin resistance. They received dietary advice and were assigned to take the capsules with or without probiotic (109-10 CFU) daily for 13 weeks. Clinical, biochemical and gut microbiome measurements were made at baseline and at the end of the intervention. RESULTS: There was a significant improvement in body mass index in all children after the intervention, suggesting that weight changes are related to the dietary advice. A significant decrease in circulating high-sensitive C-reactive protein (P = 0.026) and monocyte chemoattractant protein-1 (P = 0.032) and an increase in high-density lipoprotein cholesterol (P = 0.035) and omentin-1 (P = 0.023) in children receiving probiotic supplementation were observed compared to the control group. Regarding gut microbiota, probiotic administration significantly increased the proportion of the Rikenellaceae family members, particularly of the Alistipes genus. CONCLUSIONS: The beneficial effects of the intervention on inflammatory markers and lipid profile suggest that B. pseudocatenulatum CECT 7765 intake together with dietary recommendations can improve inflammatory status in children with obesity and insulin resistance. These effects are parallel to increases in bacterial groups associated with a lean phenotype. The modulation of gut microbiota with probiotic supplementation can be considered an effective tool to ameliorate some obesity-related disorders in children.

Impact of adenotonsillectomy on the evolution of inflammatory markers.

BACKGROUND: Tonsils are first-line host defence organs against pathogenic agents and participate in local and systemic immunity. Persistent increases in systemic inflammatory responses may contribute to associated morbidity. The aim of this study was to verify the short- and long-term impact of adenotonsillectomy on the evolution of inflammatory markers in 3- to 9-year-old children. METHODS: A prospective and longitudinal study was conducted over 1 year in 29 children who underwent tonsillectomy due to either chronic tonsillitis or adenotonsillar hypertrophy. Measurements of high-sensitivity C-reactive protein (hs-CRP) levels were taken. Levels of Th1-type cytokines [interleukin-1, interferon-γ, and tumor necrosis factor-α (TNF-α)] and anti-inflammatory Th2-type cytokines [interleukin-4, -5, -6, -10 and -13] were measured. Levels of transforming growth factor-beta (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) were also determined. The results were compared to those of 29 control children. RESULTS: At baseline, children with surgery indications presented with higher levels of hs-CRP, interleukin-1 and -10, interferon-γ, TNF-α and ICAM-1, whereas values of interleukin-4 were significantly lower than in control children. Children with severe tonsillar obstruction had higher values of interleukin-1, -4, and -5 and lower values of interleukin-10 compared with children with recurrent tonsillitis. One year after surgery, the levels except IL-4 did not show a significant difference from those obtained in the control group. The levels of hs-CRP and TNF-α decreased significantly in the first month. CONCLUSION: Children with chronic tonsillitis and/or adenotonsillar hypertrophy have significantly elevated levels of proinflammatory cytokines. Adenotonsillectomy restores the normal values of these parameters 1 year after surgery.

Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome.

Diabetes mellitus (DM) is known as one of important common endocrine disorders which could due to deregulation of a variety of cellular and molecular pathways. A large numbers studies indicated that various pathogenesis events including mutation, serin phosphorylation, and increasing/decreasing expression of many genes could contribute to initiation and progression of DM. Insulin resistance is one of important factors which could play critical roles in DM pathogenesis. It has been showed that insulin resistance via targeting a sequence of cellular and molecular pathways (eg, PI3 kinases, PPARγ co-activator-1, microRNAs, serine/threonine kinase Akt, and serin phosphorylation) could induce DM. Among of various factors involved in DM pathogenesis, microRNAs, and exosomes have been emerged as effective factors in initiation and progression of DM. A variety of studies indicated that deregulation of these molecules could change behavior of various types of cells and contribute to progression of DM. Resistin is other main factor which is known as signal molecule involved in insulin resistance. Multiple lines evidence indicated that resistin exerts its effects via affecting on glucose metabolism, inhibition of fatty acid uptake and metabolism with affecting on a variety of targets such as CD36, fatty acid transport protein 1, Acetyl-CoA carboxylase, and AMP-activated protein kinase. Here, we summarized various molecular aspects are associated with DM particularly the molecular pathways involved in insulin resistance and resistin in DM. Moreover, we highlighted exosomes and microRNAs as effective players in initiation and progression of DM.

Gut microbiota and attention deficit hyperactivity disorder: new perspectives for a challenging condition.

A bidirectional communication between the gut and the brain (gut-brain axis) is well recognized with the gut microbiota viewed as a key regulator of this cross-talk. Currently, a body of preclinical and to a lesser extent epidemiological evidence supports the notion that host-microbe interactions play a key role in brain development and function and in the etiology of neurodevelopmental disorders. Early life events and shifts away from traditional lifestyles are known to impact gut microbiota composition and function and, thereby, may increase the risk of developing neurodevelopmental disorders. Attention deficit hyperactivity disorder (ADHD) is nowadays the most prevalent neurodevelopmental disorder. Despite many years of research its etiology is unclear and its diagnosis and treatment are still challenging. Different factors reported to be associated with the risk of developing ADHD and/or linked to different ADHD manifestations have also been linked to shifts in gut microbiota composition, suggesting a link between the microbiota and the disorder. Evidence from preliminary human studies also suggests that dietary components that modulate gut microbiota may also influence ADHD development or symptoms, although further studies are warranted to confirm this hypothesis. Here, we firstly review the potential mechanisms by which the gut microbiota may regulate the brain-gut axis and influence behavior and neurodevelopmental disorders. Secondly, we discuss the current knowledge about the different factors and dietary components reported to be associated with the risk of developing ADHD or its manifestations and with shifts in gut microbiota composition. Finally, we briefly highlight the need to progress our understanding regarding the role of the gut microbiota in ADHD, since this could open new avenues for early intervention and improved management of the disease.

Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency.

Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2-18 years) diagnosed with AATD and 18 controls (aged 3-16 years).Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients.AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression.

Gut Microbiota and Risk of Developing Celiac Disease.

Gut microbiota shapes the development of the mucosal immune system and may provide protection against immune-mediated diseases. Celiac disease (CD) is a chronic inflammatory condition triggered by dietary gluten proteins, recently associated with gut microbiota alterations in cross-sectional studies comparing patients and controls. Whether or not these differences are causally related to the disease has yet to be elucidated, but evaluation of specific bacteria isolated from CD patients in experimental models suggests that they can promote an adverse response to dietary gluten, whereas other commensal bacteria can be protective. Genetic and environmental factors associated with increased CD risk have also been linked to shifts in the gut microbiota composition in infants early in life. Epigenetic mechanisms also seem to play an important role in modulating gut microbiota composition and function and, theoretically, could also influence CD risk. Here, we review the current knowledge on how host genetics, environmental factors, and epigenetic modifications could modulate gut microbiota functionality and how this may influence CD risk. Greater understanding of the role of this triad in CD onset and pathogenesis will be valuable in designing proof-of concept interventions in the gut ecosystem, with a view to improving CD management.

Association of RBP4 genetic variants with childhood obesity and cardiovascular risk factors.

BACKGROUND: Recent data suggest that retinol-binding protein 4 (RBP4) gene variants could be associated with a risk of obesity and its co-morbidities, such as metabolic syndrome, which increases the risk of developing type 2 diabetes mellitus and cardiovascular disease. OBJECTIVES: The present study examined the potential association of RBP4 single nucleotide polymorphisms (SNPs) with childhood obesity and its metabolic complications. METHODS: Four RBP4 SNPs, rs3758538 (3944A>C), rs3758539 (4406G>A), rs12265684 (12177G>C) and rs34571439 (14684T>G), were genotyped in a population of 180 Spanish Caucasian children (97 obese and 83 normal-weight children). Association of RBP4 SNPs with obesity, metabolic risk factors (blood pressure, triglycerides, high-density lipoprotein cholesterol, insulin resistance) and markers of vascular inflammation, such as high-sensitive C-reactive protein (hs-CRP), was tested. RESULTS: We found SNP rs3758538 to be associated with obesity (p = 0.007). Specifically, each copy of the minor allele C was associated with an increased risk of obesity, by more than twofold, in respect of being homozygous for the major allele A (odds ratio = 2.4; 95% confidence interval = 1.2-4.8). The rs3758538 and rs34571439 RBP4 SNPs correlated with plasma RBP4 levels. The SNPs rs12265684 and rs34571439 correlated with plasma triglyceride levels. The rs34571439 was also associated to hs-CRP levels. Marginal association of RBP4 SNPs with plasma high-density lipoprotein levels (rs34571439), blood pressure (rs12265684) and insulin resistance (rs3758539) was also observed. CONCLUSIONS: These findings suggest that childhood obesity may be associated with variations in RBP4 gene. The presence of selective SNPs in the RBP4 gene may account for metabolic complications.

Decreased glutathione and low catalase activity contribute to oxidative stress in children with α-1 antitrypsin deficiency.

BACKGROUND: Recent investigations in animal models have revealed oxidative stress and oxidative damage in the pathogenesis of alpha-1 antitrypsin deficiency (AATD). However, no data are available on the oxidative stress status and antioxidant enzyme activity in these patients. This study was aimed to analyse the oxidative stress profile and enzymatic antioxidant defence mechanisms in children with AATD. METHODS: Oxidative stress parameters and the activity of the main antioxidant enzymes were prospectively measured in serum of fifty-one children diagnosed with AATD and thirty-eight control individuals. RESULTS: Oxidative stress was increased in the serum of children with intermediate- (MZ; SZ) and high-risk (ZZ) phenotypes for developing AATD-related emphysema and/or liver disease. When compared with the control group, intermediate- and high-risk groups showed significantly lower total glutathione and reduced glutathione levels, decreased catalase activity and increased glutathione peroxidase activity leading to an accumulation of hydrogen peroxide that would explain the significantly increased levels of oxidative stress biomarkers observed in these patients. No differences were observed between the control (MM) and the low-risk (MS; SS) groups. A gradation in oxidative stress parameters was observed when patients were compared among themselves, in that the expression of the Z allele produces a higher oxidative stress status in homozygous (ZZ) than in heterozygous (MZ; SZ) patients. CONCLUSIONS: Increased oxidative stress, together with reduced antioxidant defence are involved in the pathophysiology of AATD at early stages, opening up a new rationale for the use of antioxidant therapies in the treatment of the disease.

Short Sleep Duration Is Related to Emerging Cardiovascular Risk Factors in Obese Children.

OBJECTIVE: The aim of the present study was to evaluate the influence of sleep duration on cardiovascular risk factors in obese children. METHODS: Cross-sectional analysis of 90 obese children ages 7 to 16 years. Anthropometric and clinical evaluation with specification of dietary and lifestyle habits was carried out during an office visit. Sleep duration was evaluated by the BEARS (B = bedtime issues, E = excessive daytime sleepiness, A = night awakening, R = regularity and duration of sleep, S = snoring) questionnaire on children's sleep characteristics. Sleep time adequacy by age was assessed according to the criteria of the National Sleep Foundation. Biochemical blood variables indicative of metabolic risk (glucose, lipid profile, and insulin) were obtained. Emergent new factors of metabolic risk, including high-sensitive C-reactive protein, γ-glutamyltranspeptidase, homocysteine, retinol-binding protein 4 (RBP4), thyroid-stimulating hormone (TSH), inflammatory markers, and the adipokines leptin, adiponectin, and ghrelin were also evaluated. The relations between the duration of sleep and these variables were analyzed by general lineal model analysis. Significant variables were introduced in logistic regression analysis to determine the odds ratio (OR) and 95% confidence interval (CI) of cardiometabolic factors with respect to sleep. RESULTS: Children who slept for short duration were significantly more at risk of severe central obesity. In the regression model, the mean arterial pressure (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.17, P = 0.008), homocysteine (OR 1.41, 95% CI 1.08-1.84, P = 0.013), RBP4 (OR 1.78, 95% CI 1.15-2.78, P = 0.010), and TSH (OR 2.01, 95% CI 1.21-3.34, P = 0.007) remain as significant independent predictors related to short sleep duration. We did not find any association between sleep duration and inflammatory markers or adipokines. CONCLUSIONS: Short sleep duration increases the severity of obesity and is related to cardiovascular risk factors in children.

Infrared thermography is useful for ruling out fractures in paediatric emergencies.

UNLABELLED: Musculoskeletal injuries are a leading cause of paediatric injuries and emergency department visits in Western countries. Diagnosis usually involves radiography, but this exposes children without fractures to unnecessary ionising radiation. We explored whether infrared thermography could provide a viable alternative in trauma cases. We compared radiography and thermal images of 133 children who had been diagnosed with a trauma injury in the emergency unit of a Spanish hospital. As well as the thermal variables in the literature, we introduced a new quantifier variable, the size of the lesion. Decision tree models were built to assess the technique's accuracy in diagnosing whether a bone had been fractured or not. Infrared thermography had a sensitivity of 0.91, a specificity of 0.88 and a negative predictive value of 0.95. The new lesion size variable introduced appeared to be of main importance to the discriminatory power of the method. CONCLUSION: The high negative predictive value of infrared thermography suggests that it is a promising method for ruling out fractures.