A set of pedagogical recommendations for improving the integrated approach to childhood overweight and obesity: A Delphi study

Background: Tackling the increasing global problem of childhood overweight and obesity requires an integrated approach. Studies increasingly emphasize the importance of the parents' role in interventions designed to prevent overweight in children. The aim of this study was to develop a unified set of recommendations for healthy parenting practices that can be applied by all professionals who work with children age 4-13 years and can contribute to strengthening the integrated approach to childhood overweight. Methods: A modified Delphi procedure was used to reach consensus regarding what these pedagogical recommendations should encompass. The 30 panelists were professionals and researchers who work with children age 4-13 in the domains of health care, overweight, parenting, education, nutrition, and/or sports. The procedure consisted of: i) extracting existing pedagogical recommendations from national guidelines and professional protocols, ii) appraising and prioritizing these recommendations in terms of relevance through two rounds of questionnaires, and iii) meeting to discuss and approve the set of recommendations. Results: Consensus was reached for one set of eleven pedagogical theme-based recommendations designed to support and instruct parents how to stimulate healthy energy balance-related behaviors in their child. Each recommendation contained information regarding: i) which behaviors in the child and/or parent are important, ii) why this is important, and iii) how parents can stimulate this behavior by applying parenting skills in daily life. The eleven themes were: modeling, positive parenting, breakfast, varied diet, sugar-sweetened beverages, snacks, physical activity, playing sports, quantity of screen time, screen time during meals, and sleep. Conclusion We developed a set of recommendations for healthy parenting that can be used by various professionals working with children age 4-13 and can contribute to creating an integrated approach to childhood overweight. We also developed a web-based app called “Recommendations for Healthy Parenting” as a convenient tool for following these recommendations

The effectiveness of a web-based Dutch parenting program to prevent overweight in children 9–13 years of age:Results of a two-armed cluster randomized controlled trial

INTRODUCTION: Although parental support is an important component in programs designed to prevent overweight in children, current programs pay remarkably little attention to the role of parenting. We therefore developed a web-based parenting program entitled “Making a healthy deal with your child”. This e-learning program can be incorporated into existing overweight prevention programs. The aim of this study was to determine the effectiveness of this e-learning program. MATERIALS AND METHODS: The effectiveness was examined in a two-armed cluster randomized controlled trial. The participants were 475 parent-child dyads of children 9–13 years of age in the Netherlands who participated in an existing schoolclass-based overweight prevention program. At the school grade level, parents were randomly assigned to either the intervention or the control condition. Measurements were taken from both parents and children at baseline, and 5 and 12 months after baseline. Primary outcomes included the child’s dietary and sedentary behavior, and level of physical activity. Secondary outcomes included general parenting style, specific parenting practices, and parental self-efficacy. Linear mixed effects models and generalized linear mixed effects models were conducted in R. RESULTS: Intention-to-treat analyses and completers only revealed no significant effects between the intervention and control condition on energy balance-related behaviors of the child and parenting skills after correction for multiple testing. The parents’ mean satisfaction with the e-learning program (on a 10-point scale) was 7.0±1.1. CONCLUSIONS: Although parents were generally satisfied with the parenting program, following this program had no significant beneficial effects regarding the children’s energy balance-related behaviors or the parenting skills compared to the control condition. This program may be more beneficial if used by high-risk groups (e.g. parents of children with unhealthy energy balance-related behaviors and/or with overweight) compared to the general population, warranting further study

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group. METHODS: A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings. RESULTS: In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of t

The KMT2A recombinome of acute leukemias in 2023

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5’-KMT2A, two patients had a 5’-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.publishedVersionPeer reviewe

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Cellular consequences of ATP8B1 deficiency

Mutations in the ATP8B1 gene cause a spectrum of familial intrahepatic cholestasis syndromes which we collectively refer to as ATP8B1 deficiency. Patients with ATP8B1 deficiency present with intrahepatic cholestasis (impairment of bile flow) as primary complication. These patients may also present with extrahepatic symptoms, such as diarrhea, pancreatitis and hearing loss. ATP8B1 is next to liver, also expressed in intestine, pancreas and cochlear hair cells. Aberrant ATP8B1 protein function in these tissues probably accounts for the observed extrahepatic symptoms. After more than a decade following the initial cloning of ATP8B1, we still do not fully understand how mutations in ATP8B1 mechanistically result in intrahepatic cholestasis and the extraheptic symptoms reported. ATP8B1 belongs to the family of P4 P-type ATPases (P4 ATPases), which are putative (amino-) phospholipid translocators. It is believed that P4 ATPases maintain the asymmetrical distribution of phospholipids in the plasma membrane, which is important for signal transduction, vesicular trafficking and membrane stability. These P4 ATPase-specific functions, together with the expression of ATP8B1 in tissues unrelated to bile flow, suggest that ATP8B1 plays a general role in cell physiology. The aim of this thesis was therefore to study the cellular consequences of ATP8B1 deficiency. First the question was addressed why different mutations cause ATP8B1 deficiency at the molecular level. Seven distinct ATP8B1 mutations were systematically characterized. The results indicated that most mutations resulted in protein misfolfing. Treatment with 4-phenylbutyrate, a clinically approved pharmacological chaperone, partially restored defects in expression and localization of some ATP8B1 substitutions. We propose that treatment with pharmacological chaperones may represent an effective therapeutic strategy to ameliorate cholestasis in some patients with ATP8B1 deficiency. ATP8B1 protein expression in the intestine is much more pronounced than in liver. Therefore, the cellular consequences of ATP8B1 deficiency were studied in Caco-2 cells in vitro. Caco-2 cells can be differentiated into polarized monolayers that highly resemble the intestinal epithelium. A loss of function model in Caco-2 cells was constructed by stable expression of short hairpin RNAs (shRNA) complementary to ATP8B1 mRNA. This thesis describes the recent novel insights in the cellular consequences of ATP8B1 deficiency in a model for human enterocytes. The most prominent cellular defect of ATP8B1 depletion is loss of microvilli and the reduction of expression of apically localized plasma membrane proteins. Bile salt import in ATP8B1-depleted Caco-2 cells is severely compromised, but unrelated to decreased FXR expression and function. Together, these results may clarify the etiology of diarrhea in patients with ATP8B1 deficiency. Importantly, shortening and loss of microvilli are also described in other cells with aberrant ATP8B1 protein function, such as hepatocytes and cochlear hair cells. Collectively, these data suggest that the cellular defects of ATP8B1 deficiency described in this thesis are broadly present in all epithelial cells that normally express ATP8B1. These cellular defects provide a rationale why ATP8B1 deficiency results in cholestasis and a variety of extrahepatic symptom

Personality traits as predictors of trauma-related coping self-efficacy: A three-wave prospective study [Dataset]

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Personality traits as predictors of trauma-related coping self-efficacy: A three-wave prospective study [Dataset]

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