C-reactive protein expression in adipose tissue of children with acute appendicitis.

OBJECTIVE: The aim of this study is to gain insights into the role of visceral adipose tissue as a source of C-reactive protein (CRP) in acute inflammation and to explore the potential relationship of CRP expression with the severity of appendicitis. METHODS: A total of 20 pediatric patients undergoing appendectomy were included in the study. Patients were divided into two groups according to appendicitis severity (uncomplicated and complicated). CRP levels were measured in visceral fat samples by western blotting, as well as in serum by biochemical testing. RESULTS: CRP was found to be expressed in visceral adipose tissue. The adipose tissue of patients with complicated appendicitis showed significantly higher CRP levels (p = 0.002) compared to patients with uncomplicated appendicitis. These results mirrored the CRP values obtained in serum (p = 0.018). CONCLUSION: In childhood, visceral adipose tissue is a source of CRP in acute inflammation, and its expression is potentially associated with the severity of local inflammation.

Relationship between polymorphisms in the CRP, LEP and LEPR genes and high sensitivity C-reactive protein levels in Spanish children.

BACKGROUND: We investigated the association of single nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP), leptin (LEP) and leptin receptor (LEPR) genes with high sensitivity CRP (hs-CRP) levels in two independent cohorts of healthy Spanish children. METHODS: We measured hs-CRP levels in 646 6-8-year-old and 707 12-16-year-old children using a high-sensitivity C-Reactive Protein ELISA kit. Four SNPs in the CRP gene (rs1205, rs1130864, rs2794521 and rs1800947), one SNP in the LEP gene (rs7799039) and two SNPs in the LEPR (rs1137100 and rs1137101) gene were determined by TaqMan® allelic discrimination assays. RESULTS: The four CRP SNPs studied were significantly (p<0.05) associated with hs-CRP levels in both cohorts. Furthermore, two common CRP haplotypes (constructed using the SNPs in order: rs1205, rs1130864, rs1800947, rs2794521) ACGA and GCGG were associated with significantly lower CRP levels (p<0.05) at both ages. The LEPR SNPs rs1137100 (K109R) and rs1137101 (Q223R), and LEP SNP rs7799039 (G2548A) were also associated to hs-CRP levels (p<0.05) in both cohorts. CONCLUSIONS: hs-CRP levels in healthy Spanish children, besides being associated to common polymorphisms in the CRP gene, are associated to polymorphisms in the LEP and LEPR genes, which suggests that other loci, in addition the CRP gene, may have a role determining CRP levels in children.

High-Sensitivity C-Reactive Protein and Leptin Levels Related to Body Mass Index Changes Throughout Childhood.

OBJECTIVES: To analyze the association between high-sensitivity C-reactive protein (hs-CRP) levels and cardiovascular risk factors in healthy school children, and to evaluate whether changes in body mass index (BMI) category throughout childhood affect hs-CRP levels. STUDY DESIGN: We measured serum hs-CRP levels, lipid profile, insulin levels, and leptin levels in 683 prepubertal children and 748 adolescents. A total of 272 children participated in the study in both cohorts, prepubertal (baseline; age 6-8 years) and adolescents (follow-up; age 12-16 years). RESULTS: Compared with their normal weight (NW) counterparts, hs-CRP levels were significantly higher in obese and overweight (OW) adolescents and obese prepubertal children. The highest hs-CRP levels were seen in children who were OW at baseline and at follow-up, and the lowest levels in those who transitioned from OW at baseline to NW at follow-up. High-density lipoprotein cholesterol and apolipoprotein A-I levels decreased across the hs-CRP tertile in both prepubertal children and adolescents, with significant differences (P < .001) in concentrations between the highest and lowest tertiles in 6- to 8-year-old boys and girls and in 12- to 16-year-old boys. The hs-CRP levels were also significantly associated with leptin levels in both prepubertal children and adolescents, with a significant increase across hs-CRP tertiles (P < .001). CONCLUSIONS: The shift from OW to NW throughout childhood is associated with a decrease in hs-CRP level to below that observed in children who maintain NW throughout childhood. Leptin levels were strongly associated with hs-CRP levels in our population independent of BMI. Our findings suggest that an obesity-related chronic inflammatory state may be reversible by improving weight status.

Sex-related differences in the association of ghrelin levels with obesity in adolescents.

BACKGROUND: The utility of ghrelin as a biomarker may be different depending on gender. The aim of this study was to assess ghrelin levels in a population-based sample of adolescents, and to evaluate their association with obesity and obesity-related parameters depending on sex. METHODS: The studied population included 601 randomly selected 14-to 16-year-old children. Anthropometrical data were measured and body mass index (BMI) and waist to hip ratio calculated. Body composition was assessed using an impedance body composition analyzer. Total serum ghrelin levels were determined using a multiplexed bead immunoassay. Serum leptin and adiponectin levels were determined by ELISA and insulin by RIA. RESULTS: Ghrelin levels were significantly higher in girls than in boys. Serum ghrelin concentrations were significantly lower (p<0.01) in obese than in normal weight (NW) girls, but showed no differences by weight category in boys. Ghrelin showed a significant negative relationship with waist circumference (WC), waist to hip ratio and fat mass (p<0.05) in both genders, and with weight and BMI (p<0.01) in girls, and insulin (p<0.01) and HOMA (p<0.05) in boys. Ghrelin also correlated negatively with leptin levels in girls (p<0.01). CONCLUSIONS: Our study describes serum ghrelin levels in adolescents, showing a sexual dimorphism in ghrelin levels in these 14-to 16-year-old children, and a different association of ghrelin levels with obesity by gender that suggests a different appetite and energy expenditure control depending on sex at this age.

Association of resistin polymorphisms with resistin levels and lipid profile in children.

Previous research has found a correlation between resistin and lipid level variations. Polymorphisms in the resistin gene (RETN) could be involved in this relationship, but the results of the different studies are contradictory. The aim of this study was to examine the association between resistin and lipid levels, and to determine whether resistin polymorphisms are associated with resistin levels and lipid profile in prepubertal children and adolescents. The single nucleotide polymorphisms (SNPs) rs1862513 and rs10401670 were analyzed in 442 randomly selected 6- to 8-year-old children and 827 children aged 12-16 years. Anthropometric data were recorded. Lipid profile was determined using standard methods. Serum resistin levels were measured using a multiplexed bead immunoassay. Resistin polymorphisms were determined by TaqMan(®) allelic discrimination assays. A relationship was found between serum levels of resistin and the SNP rs10401670 in 6- to 8-year-old boys. SNP rs10401670 was also related to TC and LDL-cholesterol in 12- to 16-year-old boys and to HDL-C in 12- to 16-year-old girls. SNP rs1862513 was not related to any of the studied variables. Serum resistin levels were significantly and negatively associated with ApoAI levels in 12- to 16-year-old girls. A SNP in the 3'UTR region of RETN (rs10401670) is associated with resistin levels and lipid profile in children, showing different associations depending on age and gender.

Sleep problems and circadian rhythm functioning in autistic children, autism with co-occurring attention deficit hyperactivity disorder, and typically developing children: A comparative study.

LAY ABSTRACT: Sleep problems are common in autism spectrum disorder (ASD) and different factors can contribute to its occurrence in this population. Misalignment of the biological clock (our circadian system) has been described as one possible explanation. While there is a body of research on sleep problems, relatively less is known about circadian functioning and the specific population of autistic children with co-occurring attention deficit hyperactivity disorder (ADHD). Using an ambulatory circadian monitoring (ACM) system, which resembles a common watch, we gathered sleep parameters and the different rhythms obtained from measuring motor activity, light exposure and distal temperature in 87 autistic children and adolescents, 27 of whom were diagnosed with co-occurring ADHD, and 30 neurotypical children and adolescents as a comparison group. Autistic children and, especially, those with co-occurring ADHD showed greater motor activity during sleep which would be worth studying in future projects which could better define this restless sleep. Of note, we observed an atypical pattern of wrist temperature, with higher values in neurotypical children, followed by autistic children and, ultimately, those with co-occurring ADHD. Temperature is one of the most valuable factors evaluated here as it is closely connected to sleep-wakefulness and the hormone melatonin. Its special pattern during day and nighttime would support the hypothesis of an atypical secretion of melatonin in autistic individuals which would also link with the higher presence of sleep problems in this neurodevelopmental condition.

Molecular basis of normal and pathological puberty: from basic mechanisms to clinical implications.

Puberty is a major maturational event; its mechanisms and timing are driven by genetic determinants, but also controlled by endogenous and environmental cues. Substantial progress towards elucidation of the neuroendocrine networks governing puberty has taken place. However, key aspects of the mechanisms responsible for the precise timing of puberty and its alterations have only recently begun to be deciphered, propelled by epidemiological data suggesting that pubertal timing is changing in humans, via mechanisms that are not yet understood. By integrating basic and clinical data, we provide a comprehensive overview of current advances on the physiological basis of puberty, with a particular focus on the roles of kisspeptins and other central transmitters, the underlying molecular and endocrine mechanisms, and the pathways involved in pubertal modulation by nutritional and metabolic cues. Additionally, we have summarised molecular features of precocious and delayed puberty in both sexes, as revealed by clinical and genetic studies. This Review is a synoptic up-to-date view of how puberty is controlled and of the pathogenesis of major pubertal alterations, from both a clinical and translational perspective. We also highlight unsolved challenges that will seemingly concentrate future research efforts in this active domain of endocrinology.

Sleep Problems, Circadian Rhythms, and Their Relation to Behavioral Difficulties in Children and Adolescents with Autism Spectrum Disorder.

This was an exploratory cross-sectional study comparing 45 children with ASD to 24 typically developing drug-naïve controls, group-matched on age, sex, and body mass index. Objective data was obtained using the following: an ambulatory circadian monitoring device; saliva samples to determine dim light melatonin onset (DLMO): and three parent-completed measures: the Child Behavior Checklist (CBCL); the Repetitive Behavior Scale-Revised (RBS-R); and the General Health Questionnaire (GHQ28). The CBCL and RBS-R scales showed the highest scores amongst poor sleepers with ASD. Sleep fragmentation was associated with somatic complaints and self-injury, leading to a higher impact on family life. Sleep onset difficulties were associated with withdrawal, anxiety, and depression. Those with phase advanced DLMO had lower scores for "somatic complaints"; "anxious/depressed" state; and "social problems", suggesting that this phenomenon has a protective role.

Relationship between eating habits, sleep patterns and physical activity and the degree of obesity in children and adolescents.

INTRODUCTION: Childhood obesity is an extremely prevalent pathology and, in order to be able to address it, it is necessary to understand the factors that influence on its genesis and maintenance. We hypothesise that the timing of meals and sleep, the regularity of these throughout the week and a sedentary lifestyle influence the degree of obesity. MATERIAL AND METHODS: We included children and adolescents with obesity who attended a first check-up visit at the Childhood Obesity Unit between January 2018 and February 2020. The data were obtained from a questionnaire on food (36-h intake, frequency of consumption, eating times and habits) and sleep. RESULTS: The degree of obesity was influenced to a greater extent by later meal times and the distribution of calories throughout the day (less at breakfast, more at dinner) than by the total number of calories ingested. In addition, a lower consumption of vegetables was related to a higher degree of obesity. The difference between the hours of sleep at weekends and on weekdays correlated positively with a higher degree of obesity. Finally, the anthropometric data correlated negatively with the number of hours of physical activity. Almost half of the children did not exercise after school. CONCLUSION: In the approach to childhood obesity, it is necessary to include recommendations on the regularity of meal and sleep times, as well as the distribution of calories throughout the day. Additionally, it is necessary to encourage the practice of physical exercise.

Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children.

Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with BMI and plasma lipid levels in pre-pubertal boys and girls. The study sample population comprised 1268 children aged 6-8 years. Information regarding anthropometric parameters and plasma lipid concentrations was available. Genotyping of CLOCK SNPs rs1801260, rs4580704, rs3749474, rs3736544 and rs4864548 and REV-ERBα SNPs rs2017427, rs20711570 and rs2314339 was performed by RT-PCR. The CLOCK SNPs rs3749474 and rs4864548 were significantly associated with BMI in girls but no in boys. Female carriers of the minor alleles for these SNPs presented lower BMI compared to non-carriers. A significant association of the REV-ERBα SNP rs2071570 with plasma total cholesterol, LDL-cholesterol and Apo B in males was also observed. Male AA carriers showed lower plasma levels of total cholesterol, LDL-cholesterol and Apo B levels as compared with carriers of the C allele. No significant associations between any of the studied REV-ERBα SNPs and plasma lipid levels were observed in females. In summary, CLOCK and REV-ERBα SNPs were associated with BMI and plasma lipid levels respectively in a sex-dependent manner. Our findings suggest that sex-related factors may interact with Clock genes SNPs conditioning the effects of these polymorphisms on circadian alterations.

Leptin Concentrations Determine the Association between High-Sensitivity C-Reactive Protein Levels and Body Mass Index in Prepubertal Children.

Obesity is associated with the presence of low-grade inflammation even during childhood. The dysregulation in the secretion of adipokines, such as leptin, which occurs in obesity states, could be associated with an increase in inflammatory factors already at an early age. In this cross-sectional study, we aimed to investigate the role of leptin levels in the association between body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) in healthy schoolchildren. Leptin and hs-CRP levels were analyzed in two pediatric cohorts comprising 684 prepubertal children and 763 adolescents. hs-CRP concentrations correlated significantly with BMI and leptin levels in prepubertal males and females as well as in adolescents. However, after adjusting for leptin concentration, no significant correlation was observed between hs-CRP and BMI in prepubertal children, while the correlations remained significant in adolescents. The same differences were observed when analyzed BMI according to hs-CRP tertile after adjusting for leptin; mean BMI was not significantly different between hs-CRP tertile in prepubertal children but was significantly different in adolescents. In conclusion, the fact that leptin concentrations determine the association of BMI with hs-CRP levels in prepubertal children, but not in adolescents, suggests a role for leptin in low-grade inflammation at early ages, while other factors seem to contribute to hs-CRP levels later in life.

Response to Melatonin Treatment in Children With Autism spectrum Disorder and Relationship to Sleep Parameters and Melatonin Levels.

Melatonin is one of the most used pharmacologic treatments for sleep problems in autism spectrum disorder, though its relationship with circadian and sleep parameters is still not well stablished. A naturalistic study was conducted in children with autism spectrum disorder, previously drug-naïve, before and after treatment with immediate-release melatonin. Circadian rhythms and sleep parameters were studied using an ambulatory circadian-monitoring device, and saliva samples were collected enabling determination of dim light melatonin onset. Twenty-six children with autism spectrum disorder (age 10.50 ± 2.91) were included. Immediate-release melatonin modified circadian rhythm as indicated by wrist skin temperature, showing an increase at night. A positive correlation was found between time of peak melatonin and sleep efficiency improvement values. Sleep-onset latency and efficiency improved with immediate-release melatonin. Immediate-release melatonin could be an effective treatment to improve sleep onset and restore a typical pattern of wrist temperature, which appears to be lost in autism spectrum disorder.

Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort.

BACKGROUND: In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort. RESULTS: We found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism. CONCLUSIONS: Our study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.

Precocious sexual maturation: Unravelling the mechanisms of pubertal onset through clinical observations.

Puberty is a crucial biological process normally occurring at a specific time during the lifespan, during which sexual and somatic maturation are completed, and reproductive capacity is reached. Pubertal timing is not only determined by genetics, but also by endogenous and environmental cues, including nutritional and metabolic signals. During the last decade, we have learned much regarding the essential roles of kisspeptins and the neuropeptide pathways that converge on these neurones to modulate kisspeptin signalling, as well as neurokinin B and dynorphin, the co-transmitters of Kiss1 neurones in the arcuate nucleus, and the effects of melanocortins on puberty. Indeed, melanocortins are involved in transmitting the regulatory actions of metabolic cues on pubertal maturation. Intracellular metabolic sensors, such as the AMP-activated protein kinase and the fuel-sensing deacetylase SIRT1, have been shown to contribute to puberty. Further understanding of these signals and regulatory circuits will help uncover the intimacies of the central control of puberty, as well as how alterations in metabolic status, ranging from undernutrition to obesity, affect the pubertal process. Precocious puberty is rare and has a clear female predominance. Central precocious puberty (CPP) is diagnosed when premature activation of the hypothalamic-pituitary axis occurs. Its causes are heterogeneous, with alterations of the central nervous system being of special interest, and with environmental factors also playing a role in some cases. During the last decade, several mutations in different genes (including KISS1, KISS1R, MKRN3 and DLK1) that cause CPP have been discovered. Loss-of-function mutations in MKRN3 are the most common monogenic cause of CPP known to date. Here, we review and update what is known regarding the genotype-phenotype relationship in patients with CPP.

Prevalence and risk factors associated with different comorbidities in obese children and adolescents.

INTRODUCTION: Different obesity-related comorbidities already present in childhood, such as: vitamin D deficiency, impaired carbohydrate metabolism, dyslipidaemia, arterial hypertension and non-alcoholic steatohepatitis. In this study, we aim to analyse the prevalence of comorbidities and to determine the predictive factors that affect these comorbidities. MATERIAL AND METHODS: Anthropometric, demographic and biochemical variables were collected from obese patients between six and 18 years of age. Subsequently, a statistical analysis was performed to describe the characteristics of the patients and the prevalence of comorbidities, as well as their predictive factors. RESULTS: A total of 158 obese children (76 boys and 82 girls) with a mean age at diagnosis of 12.48 years and a BMI Z-score of +3.24 SDS were included. The most prevalent comorbidities were vitamin D deficiency (64.2%), insulin resistance (45.1%), dyslipidaemia (32.2%), hyperuricaemia (18.5%) and arterial hypertension (15%). Age, BMI Z-score, percentage of fat mass and male sex have been found to be predictors of these comorbidities. CONCLUSION: Obese children and adolescents have a high prevalence of comorbidities. Once the diagnosis of obesity has been established, it would be very useful to identify early those patients with a higher risk of comorbidities, knowing their relationship with sex, age, BMI Z-score, percentage of fat mass and pubertal stage.

Melatonin Rhythm and Its Relation to Sleep and Circadian Parameters in Children and Adolescents With Autism Spectrum Disorder.

Introduction: Sleep problems are prevalent among individuals with autism spectrum disorder (ASD), and a role has been attributed to melatonin in this multifactorial comorbidity. Methods: A cross-sectional study was conducted on 41 autistic children and adolescents (9.9 ± 3.02) and 24 children and adolescents with a normal intellectual function (8.42 ± 2.43) were used as controls. Subjects were matched for sex, body mass index, and pubertal stage, and all were drug-naive. Circadian and sleep parameters were studied using an ambulatory circadian monitoring (ACM) device, and saliva samples were collected around the onset of sleep to determine dim light melatonin onset (DLMO). Results: Prepubertal individuals with ASD presented later DLMO and an earlier decline in melatonin during adolescence. A relationship was found between melatonin and both sleep and circadian parameters. Participants and controls with later DLMOs were more likely to have delayed sleep onset times. In the ASD group, subjects with the later daytime midpoint of temperature had a later DLMO. Later melatonin peak time and DLMO time were related to lower general motor activity and lower stability of its rhythms. Conclusion: The melatonin secretion pattern was different in individuals with ASD, and it showed a relationship with sleep and circadian parameters. Alterations in DLMO have not been previously reported in ASD with the exception of more variable DLMO timing; however, high variability in the study design and sample characteristics prevents direct comparison. The ACM device enabled the measurement of circadian rhythm, a scarcely described parameter in autistic children. When studied in combination with other measures such as melatonin, ACM can offer further knowledge on sleep problems in ASD.

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children.

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6-8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables.

Association of ACE2 Polymorphisms and Derived Haplotypes With Obesity and Hyperlipidemia in Female Spanish Adolescents.

Background: In the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, ACE2 exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. The aim of this study was to analyse the relationship of ACE2 polymorphisms with cardiovascular risk factors in children. Methodology: Five ACE2-single nucleotide polymorphisms (SNP), rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related to CV risk factors, were analyzed in a representative sample of 12-16-year-old children and tested for their potential association with anthropometric parameters, insulin levels and the lipid profile. Results: Girls (N = 461) exhibited lower rates of overweight, obesity, blood pressure, and glycemia than boys (N = 412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02-2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04-2.68)]. Also, TG levels were linked to the rs879922, rs233575, and rs2158083 SNPs, and the TG/HDL-C ratio was associated with rs879922 and rs233575. Levels of TC and LDL-C were associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG ≥ 90 mg/dL was related to rs879922 [OR 1.78 (1.06-2.96)], rs2158083 [OR 1.75 (1.08-2.82)], and rs233575 [OR 1.62 (1.00-2.61)]. The cut-off level for TC ≥ 170 mg/dL was associated with rs2074192 OR 1.54 (1.04-2.28) and rs2158083 [OR 1.53 (1.04-2.25)]. Additionally, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related to higher prevalence of overweight/obesity and TG elevation. Conclusion: The expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, the ACE2-SNPs rs879922, rs233575, rs2158083 and rs2074192, and the haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.

Sleep Problems and Circadian Functioning in Children and Adolescents With Autism Spectrum Disorder.

BACKGROUND: Sleep problems are a prevalent comorbidity in autism spectrum disorder (ASD) with a multifactorial basis in which circadian misalignment has been described. METHODS: A cross-sectional study was conducted including 52 children and adolescents with ASD (9.85 ± 3.07) and 27 children and adolescent controls with normal intellectual functioning (8.81 ± 2.14). They were matched for age, sex, and body mass index, and all were drug-naïve. An ambulatory circadian monitoring device was used to record temperature and motor, body position, sleep, and light intensity. RESULTS: Individuals with ASD presented longer sleep-onset latency, lower sleep efficiency, and decreased total sleep time and tended to be more sedentary and have less exposure to light. They also showed lower amplitude, low interdaily stability, and a different pattern of wrist temperature across the day, with a midpoint of sleep that did not concur with sleep midpoint indicated by the rest of circadian parameters. CONCLUSIONS: The sleep problems observed in this sample resemble those reported previously, with the exception of nocturnal awakenings which did not show differences. The ambulatory circadian monitoring device enabled measurement of circadian parameters such as temperature which, until now, were scarcely described in children with ASD and could be used to better understand sleep and circadian system in ASD.