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IScience Jun 2024Obesity, characterized by enlarged and dysfunctional adipose tissue, is among today's most pressing global public health challenges with continuously increasing...
Obesity, characterized by enlarged and dysfunctional adipose tissue, is among today's most pressing global public health challenges with continuously increasing prevalence. Despite the importance of post-translational protein modifications (PTMs) in cellular signaling, knowledge of their impact on adipogenesis remains limited. Here, we studied the temporal dynamics of transcriptome, proteome, central carbon metabolites, and the acetyl- and phosphoproteome during adipogenesis using LC-MS/MS combined with PTM enrichment strategies on human (SGBS) and mouse (3T3-L1) adipocyte models. Both cell lines exhibited unique PTM profiles during adipogenesis, with acetylated proteins being enriched for central energy metabolism, while phosphorylated proteins related to insulin signaling and organization of cellular structures. As candidates with strong correlation to the adipogenesis timeline we identified CD44 and the acetylation sites FASN_K673 and IDH_K272. While results generally aligned between SGBS and 3T3-L1 cells, details appeared cell line specific. Our datasets on SGBS and 3T3-L1 adipogenesis dynamics are accessible for further mining.
PubMed: 38840842
DOI: 10.1016/j.isci.2024.109711 -
Translational Pediatrics May 2024Prader-Willi syndrome (PWS) is a multisystem genetic disorder caused by chromosomal imprinting gene defects, with approximately 70% of cases resulting from paternal...
BACKGROUND
Prader-Willi syndrome (PWS) is a multisystem genetic disorder caused by chromosomal imprinting gene defects, with approximately 70% of cases resulting from paternal deletion of the chromosomal region 15. The main clinical features include severe infantile hypotonia, early-onset childhood obesity, hyperphagia, and underdeveloped external genitalia. As individuals with PWS age, they may exhibit irritability, social dysfunction, impaired gonadal development, and metabolic syndrome. Previous literature places the prevalence of type 2 diabetes mellitus (T2DM) in PWS at approximately 7-24%. Oxytocin is a neuropeptide secreted by the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus and regulates energy metabolism, which is involved in PWS. Due to age limitations, very few patients progress to diabetic nephropathy during childhood, and reports of typical diabetic nephropathy in PWS during childhood are extremely rare. Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist which can be used in the treatment of T2DM.
CASE DESCRIPTION
This article reports a case of a child with PWS complicated by stage III diabetic nephropathy, providing a retrospective analysis of the diagnosis and treatment process, as well as a review of domestic and international literature, to enhance understanding of this condition. And this article provides a treatment idea for PWS patients with diabetic nephropathy.
CONCLUSIONS
It is very important to enhance understanding of PWS. And we offer new diagnostic and possible therapeutic approaches for pediatric patients with diabetic nephropathy.
PubMed: 38840685
DOI: 10.21037/tp-23-518 -
Nature Jun 2024Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs), which influences offspring development and adult phenotypes. Whether...
Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs), which influences offspring development and adult phenotypes. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
Topics: Animals; Male; Spermatozoa; Mice; RNA, Mitochondrial; Female; Epigenesis, Genetic; Diet, High-Fat; Humans; RNA, Transfer; Epididymis; Testis; RNA, Small Untranslated; Mitochondria; Obesity; Oocytes; Embryo, Mammalian; Fertilization; Overweight; Mice, Inbred C57BL; Paternal Inheritance
PubMed: 38839949
DOI: 10.1038/s41586-024-07472-3 -
CPT: Pharmacometrics & Systems... Jun 2024Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with...
Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. Physiologically-based PK (PBPK) models are an attractive alternative that can account for physiologic-, genetic-, and drug-specific changes without the need for extensive clinical trial data. In this study, we explored the effect of obesity on pantoprazole PK and evaluated label-suggested dosing in this population. An adult PBPK model for pantoprazole was developed using data from the literature and accounting for genetic variation in CYP2C19. The adult PBPK model was scaled to children without obesity using age-associated changes in anatomical and physiological parameters. Lastly, the pediatric PBPK model was expanded to children with obesity. Three pantoprazole dosing strategies were evaluated: 1 mg/kg total body weight, 1.2 mg/kg lean body weight, and US Food and Drug Administration-recommended weight-tiered dosing. Simulated concentration-time profiles from our model were compared with data from a prospective cohort study (PAN01; NCT02186652). Weight-tiered dosing resulted in the most (>90%) children with pantoprazole exposures in the reference range, regardless of obesity status or CYP2C19 phenotype, confirming results from previously published population PK models. PBPK models may allow for the efficient study of physiologic and developmental effects of obesity on PK in special populations where clinical trial data may be limited.
PubMed: 38837864
DOI: 10.1002/psp4.13167 -
Minerva Pediatrics Jun 2024Pediatric obesity represents one of the most important public health challenges and its prevalence significantly increased during the COVID-19 pandemic. Our prospective...
BACKGROUND
Pediatric obesity represents one of the most important public health challenges and its prevalence significantly increased during the COVID-19 pandemic. Our prospective study aimed to assess the feasibility of a remote adapted physical activity (PA) intervention and its effectiveness in improving anthropometric indices, metabolic health parameters, as well as cardiopulmonary function and fitness in adolescents with obesity.
METHODS
A PA intervention involving synchronous online lessons combined with asynchronous sessions and promotion of independent PA and "active breaks" to interrupt prolonged sedentary behaviors was proposed to 20 adolescents aged 11-17 years with obesity over a 4-month period. Clinical and anthropometric parameters (weight, height, waist, body composition, blood pressure), metabolic parameters (glycemia, insulinemia, glycated hemoglobin, oral glucose tolerance test [OGTT], lipid profile, presence of hepatic steatosis), cardiopulmonary function and fitness indices (VO
2 max, six-minute walking test [6MWT], upper and lower limb strength test) were evaluated before and after the intervention.RESULTS
Twenty adolescents with obesity were enrolled (11 male [55%], aged 14.1±1.5 years, BMI SDS 3.1±0.5). Eighteen participants (90%) successfully completed the project, and no adverse events were reported. We observed an increase in cardiovascular and muscle fitness [higher VO2peak, maximal workload, better performance at limb strength and 6MWT (all P<0.05)], increased lean body mass (P=0.005), and an improvement of glucose metabolism response with a reduction of insulin concentrations during OGTT (P=0.043).
CONCLUSIONS
Participation in the training program was feasible and effective in improving cardiovascular fitness, glucose metabolism, body composition, strength, and endurance in adolescents with obesity during the COVID-19 pandemic.
PubMed: 38837204
DOI: 10.23736/S2724-5276.23.07469-4 -
Acta Medica Philippina 2024For several decades now, the use of uncuffed endotracheal tube (ETT) is the gold standard in providing airway and ventilatory support to children under anesthesia....
BACKGROUND
For several decades now, the use of uncuffed endotracheal tube (ETT) is the gold standard in providing airway and ventilatory support to children under anesthesia. However, there has been a change in focus from the application of uncuffed ETT to cuffed ETT among children, and this matter has been debated for years. In fact, several studies have shown that even across and within countries, the attitudes and practices of anesthesiologists on the use of types of endotracheal tubes differed.
OBJECTIVE
To describe the current attitudes and practices of anesthesiologists regarding the use of uncuffed or cuffed ETT for children.
METHODS
A systematic review of observational studies on the current attitudes and practices of pediatric anesthesiologists regarding the use of cuffed and uncuffed ETT was conducted from May to November 2020. Cochrane reviews, Medline, Pubmed, and EMBASE were searched and yielded five relevant studies.
RESULTS
The use of cuffed ETT ranged between 11%-61% in the included studies and all reported that there were no consensus or standard on whether cuffed or uncuffed ETT was better. Reported factors for cuffed ETT use included: 1) Personal choice, 2) Department protocol, 3) Availability of resources, and 4) Specific conditions such as obesity, planned or emergency procedure, and reduced lung compliance. In terms of ETT size, reported criteria were: 1) Use of a formula, 2) Use of abacus/calculator, and 3) In relation to the fifth finger's width.
CONCLUSIONS
The current systematic review demonstrated that there is wide variation in current attitudes and practices of anesthesiologists regarding the use of uncuffed or cuffed endotracheal tubes in children. Likewise, factors affecting choice of ETT and criteria for selection varied in the published literature. The results of this systematic review highlight the need for a standard guideline to help clinicians choose if cuffed or uncuffed ETT is better in certain scenarios and to help them decide in selecting the most appropriate ETT size.
PubMed: 38836076
DOI: 10.47895/amp.v58i9.8743 -
Anales de Pediatria Jun 2024Management of childhood obesity, based upon behavioural, physical activity and dietary guidance, usually achieves limited success and is hindered by a high attrition...
INTRODUCTION
Management of childhood obesity, based upon behavioural, physical activity and dietary guidance, usually achieves limited success and is hindered by a high attrition rate. The identification of potential predictors of either weight loss or early weight management attrition could help develop personalised management plans in order to improve patient outcomes.
PATIENTS AND METHODS
We conducted a retrospective study in a cohort of 1300 patients with obesity managed in speciality clinics for up to 5 years with outpatient conservative treatment. We studied the family background and personal characteristics (demographic, behavioural, psychosocial, anthropometric and metabolic) of patients who dropped out before completing the first year of the programme and patients who achieved significant weight loss, with a separate analysis of patients who achieved substantial reductions in weight compared to the rest of the cohort.
RESULTS
The mean age of the patients in the cohort was 10.46 years (SD, 3.48) the mean BMI z-score 4.01 (SD, 1.49); 52.8% of the patients were male, 53.3% were prepubertal, 75.8% were Caucasian and 19% Latin. We found a higher proportion of Latinla ethnicity and compulsive eating in the group of patients with early attrition from the weight management follow-up. In the group of patients with substantial weight loss, a greater proportion were male, there was a higher frequency of dietary intake control at home and obesity was more severe, and the latter factor was consistently observed in patients who achieved substantial weight loss at any point of the follow-up.
CONCLUSIONS
Some family and personal characteristics in childhood obesity are associated with an increased risk of early withdrawal from follow-up or a greater probability of successful outcomes; however, the predictive value of these variables is limited.
Topics: Humans; Male; Pediatric Obesity; Female; Retrospective Studies; Child; Patient Compliance; Follow-Up Studies; Treatment Outcome; Adolescent; Weight Loss
PubMed: 38834436
DOI: 10.1016/j.anpede.2024.05.007 -
Frontiers in Public Health 2024Less than one-quarter of US children meet physical activity (PA) guidelines. Understanding the context in which PA occurs and how these contexts may play a role in...
Examining associations between physical activity context and children meeting daily physical activity guidelines: the role of outdoor play, sports, and other organized activities.
BACKGROUND
Less than one-quarter of US children meet physical activity (PA) guidelines. Understanding the context in which PA occurs and how these contexts may play a role in meeting PA guidelines is an essential step toward developing effective behavioral interventions. The purpose of this study was to examine associations between PA context (sports participation, participation in other organized physical activities, active travel to school, and outdoor play) and the number of days children met PA guidelines in a representative sample of children living in Texas.
METHODS
We analyzed cross-sectional data from a statewide sample of fourth-grade children in Texas who completed the 2019-2020 Texas School Physical Activity and Nutrition (Texas SPAN) survey. The Texas SPAN survey was designed to monitor the statewide prevalence of overweight/obesity among school children and assess habitual self-reported obesity-related behaviors, including diet and PA. Weighted Poisson regression models were employed to examine the associations between PA contexts (sports participation, participation in other organized physical activities, active travel to school, and outdoor play) and the number of days children met PA guidelines, adjusting for sex, race/ethnicity, overweight/obesity, urban-rural status, and economic disadvantage.
RESULTS
A total of 16.7% of fourth-grade children met physical activity guidelines every day during the week (mean age = 9.4 ± 0.6 years; female = 48.7, 51.8% Hispanic, mean days meeting PA guideline = 3.6 ± 2.3 days). One in ten (11.2%) children did not meet daily PA guidelines on any day of the week, and 72.1% met them between 1 and 6 days. Participating in sports (b = 0.22, 95%CI:0.14, 0.30), any other organized physical activities (b=0.13, 95%CI:0.017, 0.19), and playing outdoors 1-3 days (b = 0.25, 95%CI:0.04, 0.46) and 4-7 days in the past week (b = 0.77, 95%CI:0.57, 0.97) was significantly and positively associated with the number of days children met PA guidelines.
CONCLUSION
Participating in sports, participating in other organized physical activities, and playing outdoors may beneficially influence the number of days children meet PA guidelines. PA programs should consider these contextual factors and investigate how to promote organized activities and outdoor play effectively and appropriately among children.
Topics: Humans; Child; Female; Male; Exercise; Cross-Sectional Studies; Sports; Texas; Pediatric Obesity; Play and Playthings; Schools
PubMed: 38832232
DOI: 10.3389/fpubh.2024.1352644 -
Journal of Children's Orthopaedics Jun 2024The etiology and risk factors of congenital vertebral anomalies are mainly unclear in isolated cases. Also, there are no reports on the risk factors for different...
BACKGROUND
The etiology and risk factors of congenital vertebral anomalies are mainly unclear in isolated cases. Also, there are no reports on the risk factors for different subgroups of vertebral anomalies. Therefore, we assessed and identified potential maternal risk factors for these anomalies and hypothesized that diabetes, other chronic diseases, smoking, obesity, and medication in early pregnancy would increase the risk of congenital vertebral anomalies.
METHODS
All cases with congenital vertebral anomalies were identified in the Finnish Register of Congenital Malformations from 1997 to 2016 for this nationwide register-based case-control study. Five matched controls without vertebral malformations were randomly selected. Analyzed maternal risk factors included maternal age, body mass index, parity, smoking, history of miscarriages, chronic diseases, and prescription drug purchases in early pregnancy.
RESULTS
The register search identified 256 cases with congenital vertebral malformations. After excluding 66 syndromic cases, 190 non-syndromic malformations (74 formation defects, 4 segmentation defects, and 112 mixed anomalies) were included in the study. Maternal smoking was a significant risk factor for formation defects (adjusted odds ratio 2.33, 95% confidence interval 1.21-4.47). Also, pregestational diabetes (adjusted odds ratio 8.53, 95% confidence interval 2.33-31.20) and rheumatoid arthritis (adjusted odds ratio 13.19, 95% confidence interval 1.31-132.95) were associated with mixed vertebral anomalies.
CONCLUSION
Maternal pregestational diabetes and rheumatoid arthritis were associated with an increased risk of mixed vertebral anomalies. Maternal smoking increases the risk of formation defects and represents an avoidable risk factor for congenital scoliosis.
LEVEL OF EVIDENCE
III.
PubMed: 38831858
DOI: 10.1177/18632521241235027 -
PloS One 2024Parental feeding practices (PFPs) play a key role in fostering preschoolers' dietary habits and in mitigating the risk of childhood obesity. Nevertheless, parents often... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Parental feeding practices (PFPs) play a key role in fostering preschoolers' dietary habits and in mitigating the risk of childhood obesity. Nevertheless, parents often employ inappropriate feeding practices, leading to children's potential nutrition-related issues. Thus, research is needed to inform interventions that focus on optimizing feeding practices.
METHODS
This protocol describes the evaluation of a novel intervention-Empowering Parents to Optimize Feeding Practices (EPO-Feeding Program). The program will be evaluated with a two-arm feasibility randomized controlled trial (RCT) in Yangzhou, China. The program includes four weekly group-based training sessions led by healthcare professionals for parents of preschool children. The intervention incorporates sessions, group discussions, motivational interviewing, and supplementary materials (e.g., key messages and educational videos) aimed at enhancing parents' knowledge, skills, and behaviours related to feeding practices. The primary outcomes include i) implementation feasibility, primarily assessed through retention rates; and ii) program acceptability through a survey and qualitative process evaluation. Secondary outcomes encompass the potential impacts on i) PFPs, ii) parental perception of child weight (PPCW), iii) parenting sense of competence, iv) children's eating behaviours, and v) child weight status. Quantitative analyses include descriptive estimates for evaluating the feasibility and linear mixed regression analysis for testing the potential effects. Qualitative valuation will use thematic framework analysis.
DISCUSSION
If this study shows this program to be feasible to implement and acceptable to parents, it will be used to inform a fully powered trial to determine its effectiveness. The research will also help inform policy and practices in the context of child nutrition promotion, particularly regarding implementing group-based training sessions by healthcare providers in similar settings.
TRIAL REGISTRATION
Clinicaltrials.gov, Protocol #NCT06181773, 20/11/2023.
Topics: Humans; Child, Preschool; Feeding Behavior; Parents; Feasibility Studies; Female; Male; Parenting; Pediatric Obesity; China
PubMed: 38829882
DOI: 10.1371/journal.pone.0304707