Waist circumference provides an indication of numerous cardiometabolic risk factors in adults with cerebral palsy

This article has been made available through the Brunel Open Access Publishing Fund.Objective: To report the prevalence of cardiometabolic risk factors in a cohort of adults with cerebral palsy (CP) and to investigate the ability of anthropometric measures to predict these factors. Design: Cross-sectional study. Setting: Testing took place in a laboratory setting. Participants: Adults with CP (NZ55; mean age, 37.5 13.3y; Gross Motor Function Classification System levels, IeV) participated in this study. Interventions: Not applicable. Main Outcome Measures: Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, and C-reactive protein levels were measured from a fasting venous blood sample. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA-IR) index. Blood pressure, body mass index (BMI), waist circumference (WC), waist-hip ratio, and waist-height ratio were also measured. The metabolic syndrome (MetS) was defined according to the 2009 Joint Interim Statement. Results: The prevalence of the MetS was 20.5% in ambulatory adults and 28.6% in nonambulatory adults. BMI was associated with HOMA-IR only (bZ.451; P<.01). WC was associated with HOMA-IR (bZ.480; P<.01), triglycerides (bZ.450; P<.01), and systolic blood pressure (bZ.352; P<.05). Receiver operating characteristic curve analysis revealed that WC provided the best indication of hypertensive blood pressure, dyslipidemia, HOMA-IR, and the presence of multiple risk factors (area under the curve, .713e.763). Conclusions: A high prevalence of the MetS was observed in this relatively young sample of adults with CP. WC was a better indicator of a number of risk factors than was BMI and presents as a clinically useful method of screening for cardiometabolic risk among adults with CP

Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

Transition from child to adult services for young people with cerebral palsy in Ireland: Influencing factors at multiple ecological levels

Data availability statement: Data available in article supplementary material.Copyright © 2023 The Authors. Aim: To explore the factors that influence the process of transitioning from child to adult services in Ireland among young people with cerebral palsy, their parents, and service providers. Method: This study followed a qualitative descriptive approach. Semi-structured interviews were conducted with 54 participants, including young people with cerebral palsy aged 16 to 22 years (n = 13), their parents (n = 14), and service providers (n = 27). Data were analysed using the Framework Method. Findings were categorized using an ecological model across four levels: individual, microsystem, mesosystem, and exosystem. Results: Limited awareness, preparation, and access to information hindered successful transition. Microsystem factors such as family knowledge, readiness, resilience, and health professional expertise influenced transition experience. Mesosystem factors encompassed provider–family interaction, interprofessional partnerships, and interagency collaboration between child and adult services. Exosystem factors included inadequate availability and distribution of adult services, limited referral options, coordination challenges, absence of transition policies, staffing issues, and funding allocation challenges. Interpretation: Transition is influenced by diverse factors at multiple ecological levels, including interactions within families, between health professionals, and larger systemic factors. Given the complexity of transition, a comprehensive multi-level response is required, taking into account the interactions among individuals, services, and systems.Health Research Board and the Central Remedial Clinic. Grant Number: APA-2019-004; Article Funding Open access funding provided by IReL

Unmet health needs among young adults with cerebral palsy in Ireland: A cross-sectional study

Data Availability Statement: The data that support the findings of this study are openly available in Zenodo at https://doi.org/10.5281/zenodo.6968034.Copyright: © 2022 by the authors. Data describing the unmet health needs of young adults with cerebral palsy (CP) may support the development of appropriate health services. This study aimed to describe unmet health needs among young adults with CP in Ireland and examine if these differed between young adults who were and were not yet discharged from children’s services. In this cross-sectional study, young adults with CP aged 16–22 years completed a questionnaire assessing unmet health needs. Logistic regression was used to examine the association between discharge status and unmet health needs. Seventy-five young adults (mean age 18.4 yr; 41% female; 60% in GMFCS levels I-III) were included in the study. Forty (53%) had been discharged from children’s services. Unmet health need, as a proportion of those with needs, was highest for speech (0.64), followed by epilepsy (0.50) and equipment, mobility, control of movement and bone or joint problems (0.39 or 0.38). After adjusting for ambulatory status, unmet health needs did not differ according to discharge status. The proportion of young adults with unmet health needs highlights the importance of taking a life-course approach to CP and providing appropriate services to people with CP regardless of age.Health Research Board and the Central Remedial Clinic (APA-2019-004)

Transition from child to adult health services for young people with cerebral palsy in Ireland: A mixed methods study protocol

Supplementary Data: This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.Copyright information © Author(s) (or their employer(s)) 2020. Introduction The transition from child to adult health services is a challenging and complex process for young people with cerebral palsy (CP). Poorly managed transition is associated with deterioration in health, increased hospitalisations and reduced quality of life. While international research identifies key practices that can improve the experience and outcomes of transition, there is a paucity of data in the Irish context. This research study aims to gain an insight into the experience of transition for young people with CP in Ireland. Methods and analysis A convergent parallel mixed-methods design will be used to collect, analyse and interpret quantitative and qualitative data. Participants will be young people aged 16–22 years with CP, their parent(s)/carer(s) and service providers. Quantitative and qualitative data will be collected through questionnaires and interviews, respectively. Quantitative data will be reported using descriptive statistics. Where sufficient data are collected, we will examine associations between the experience of transition practices and sociodemographic and CP-related factors, respectively, using appropriate regression models. Associations between service provider characteristics and provision of key transition practices may also be explored using appropriate regression models. Qualitative data will be analysed using the Framework Method. A coding matrix based on key transitional practices identified from the literature will be used to identify convergence and divergence across study components at the integration stage. Ethics and dissemination The study has been approved by the RCSI University of Medicine and Health Sciences Research Ethics Committee (REC201911010). Results will be presented to non-academic stakeholders through a variety of knowledge translation activities. Results will be published in open access, peer-reviewed journals and presented at national and international scientific conferences.Health Research Board, grant number APA-2019–004. The study sponsor is RCSI University of Medicine and Health Sciences

Transition to adult services experienced by young people with cerebral palsy: A cross‐sectional study

Aim: To assess if young people with cerebral palsy experience and health profession-als provide practices that may improve transition from child to adult health services.Method: Seventy-five young people (31 females, 44 males; mean age 18 years 5 months [standard deviation 2 years 2 months]) and/or parents and 108 health professionals completed a questionnaire describing their experience or the provision of nine tran-sition practices.Results: The percentage of young people reporting each practice was: appropriate parent involvement (90%); promotion of health self-efficacy (37%); named worker who supports the transition process (36%); self-management support for physical health (36%); self-management support for mental health (17%); information about the transition process (24%); meeting the adult team (16%); and life skills training (16%). Post-discharge, 10% of young people reported that their general practitioner (GP) received a discharge letter. The percentage of health professionals reporting each practice was: promotion of health self-efficacy (73.2%); self-management support (73.2%); information (69%); consulting the parent and young person about parent involvement (63% and 66%); discharge letter to a GP (55%); life skills training (36%); named worker (35%); meeting the adult team (30%); and senior manager (20%).Interpretation: Many young people did not experience practices that may improve the experience and outcomes of transition. Young people should be involved in the development and delivery of transition to ensure it meets their needs.Open access funding provided by IReL. This research was funded by the Health Research Board and the Central Remedial Clinic (no. APA-2019-004)

In Vivo Delivery of Gremlin siRNA Plasmid Reveals Therapeutic Potential against Diabetic Nephropathy by Recovering Bone Morphogenetic Protein-7

Diabetic nephropathy is a complex and poorly understood disease process, and our current treatment options are limited. It remains critical, then, to identify novel therapeutic targets. Recently, a developmental protein and one of the bone morphogenetic protein antagonists, Gremlin, has emerged as a novel modulator of diabetic nephropathy. The high expression and strong co-localization with transforming growth factor- β1 in diabetic kidneys suggests a role for Gremlin in the pathogenesis of diabetic nephropathy. We have constructed a gremlin siRNA plasmid and have examined the effect of Gremlin inhibition on the progression of diabetic nephropathy in a mouse model. CD-1 mice underwent uninephrectomy and STZ treatment prior to receiving weekly injections of the plasmid. Inhibition of Gremlin alleviated proteinuria and renal collagen IV accumulation 12 weeks after the STZ injection and inhibited renal cell proliferation and apoptosis. In vitro experiments, using mouse mesangial cells, revealed that the transfect ion of gremlin siRNA plasmid reversed high glucose induced abnormalities, such as increased cell proliferation and apoptosis and increased collagen IV production. The decreased matrix metalloprotease level was partially normalized by transfection with gremlin siRNA plasmid. Additionally, we observed recovery of bone morphogenetic protein-7 signaling activity, evidenced by increases in phosphorylated Smad 5 protein levels. We conclude that inhibition of Gremlin exerts beneficial effects on the diabetic kidney mainly through maintenance of BMP-7 activity and that Gremlin may serve as a novel therapeutic target in the management of diabetic nephropathy

An NF-κB and Slug Regulatory Loop Active in Early Vertebrate Mesoderm

BACKGROUND: In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2) appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT) and to suppress apoptosis. METHODOLOGY & PRINCIPLE FINDINGS: Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IκB kinase-mediated activation of the bipartite transcription factor NF-κB. NF-κB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-κB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. CONCLUSIONS/SIGNIFICANCE: These studies reveal a Slug/Snail–NF-κB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease

Peroxiredoxin1, a novel regulator of pronephros development, influences retinoic acid and Wnt signaling by controlling ROS levels

Peroxiredoxin1 (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins. Prdx1 catalyzes the reduction of H2O2 and alkyl hydroperoxide and plays an important role in different biological processes. Prdx1 also participates in various age-related diseases and cancers. In this study, we investigated the role of Prdx1 in pronephros development during embryogenesis. Prdx1 knockdown markedly inhibited proximal tubule formation in the pronephros and significantly increased the cellular levels of reactive oxygen species (ROS), which impaired primary cilia formation. Additionally, treatment with ROS ( H2O2) severely disrupted proximal tubule formation, whereas Prdx1 overexpression reversed the ROS-mediated inhibition in proximal tubule formation. Epistatic analysis revealed that Prdx1 has a crucial role in retinoic acid and Wnt signaling pathways during pronephrogenesis. In conclusion, Prdx1 facilitates proximal tubule formation during pronephrogenesis by regulating ROS levels