Search

BackgroundThe use of technology to support health and health care has grown rapidly in the last decade across all ages and medical specialties. Newly developed eHealth tools are being implemented in long-term management of growth failure in children, a low prevalence pediatric endocrine disorder. ObjectiveOur objective was to create a framework that can guide future implementation and research on the use of eHealth tools to support patients with growth disorders who require growth hormone therapy. MethodsA total of 12 pediatric endocrinologists with experience in eHealth, from a wide geographical distribution, participated in a series of online discussions. We summarized the discussions of 3 workshops, conducted during 2020, on the use of eHealth in the management of growth disorders, which were structured to provide insights on existing challenges, opportunities, and solutions for the implementation of eHealth tools across the patient journey, from referral to the end of pediatric therapy. ResultsA total of 815 responses were collected from 2 questionnaire-based activities covering referral and diagnosis of growth disorders, and subsequent growth hormone therapy stages of the patient pathway, relating to physicians, nurses, and patients, parents, or caregivers. We mapped the feedback from those discussions into a framework that we developed as a guide to integration of eHealth tools across the patient journey. Responses focused on improved clinical management, such as growth monitoring and automation of referral for early detection of growth disorders, which could trigger rapid evaluation and diagnosis. Patient support included the use of eHealth for enhanced patient and caregiver communication, better access to educational opportunities, and enhanced medical and psychological support during growth hormone therapy management. Given the potential availability of patient data from connected devices, artificial intelligence can be used to predict adherence and personalize patient support. Providing evidence to demonstrate the value and utility of eHealth tools will ensure that these tools are widely accepted, trusted, and used in clinical practice, but implementation issues (eg, adaptation to specific clinical settings) must be addressed. ConclusionsThe use of eHealth in growth hormone therapy has major potential to improve the management of growth disorders along the patient journey. Combining objective clinical information and patient adherence data is vital in supporting decision-making and the development of new eHealth tools. Involvement of clinicians and patients in the process of integrating such technologies into clinical practice is essential for implementation and developing evidence that eHealth tools can provide value across the patient pathway.

Several high‐risk medical devices for children have become unavailable in the European Union (EU), since requirements and costs for device certification increased markedly due to the EU Medical Device Regulation. The EU‐funded CORE‐MD project held a workshop in January 2023 with experts from various child health specialties, representatives of European paediatric associations, a regulatory authority and the European Commission Directorate General Health and Food Safety. A virtual follow‐up meeting took place in March 2023. We developed recommendations for investigation of high‐risk medical devices for children building on participants' expertise and results of a scoping review of clinical trials on high‐risk medical devices in children. Approaches for evaluating and certifying high‐risk medical devices for market introduction are proposed. [ABSTRACT FROM AUTHOR]

Xanthine oxidoreductase (XOR) catalyzes the final reactions of purine catabolism and may account for cell damage by producing reactive oxygen metabolites in cells reoxygenated after hypoxia. We found a three- to eightfold higher XOR activity in cultured human bronchial epithelial cells exposed to hypoxia (0.5-3% [O.sup.2]) compared with cells grown in normoxia (21% [O.sup.2]) but no difference in XOR protein or mRNA. XOR promoter constructs failed to respond to hypoxia. The cellular XOR activity at 3% [O.sup.2] returned to basal levels when the cells were returned to 21% [O.sup.2], and hyperoxia (95% [O.sup.2]) abolished enzyme activity with no change in XOR protein. Our data suggest reversible enzyme inactivation by oxygen or its metabolites. NADH was normally oxidized by the oxygen-inactivated enzyme, which rules out damage to the flavin adenine dinucleotide cofactor. Hydrogen peroxide partially inactivated the molybdenum center of XOR, as shown by a parallel decrease in XOR-catalyzed xanthine oxidation and dichlorophenolindophenol reduction. We conclude that the transcription or translation of XOR is not influenced by hypoxia or hyperoxia. Instead, the molybdenum center of XOR is posttranslationally inactivated by oxygen metabolites in 'normal' (21% [O.sup.2]) cell culture atmosphere. This inactivation is reversed in hypoxia and accounts for the apparent induction. xanthine oxidase; hypoxia; hyperoxia; ischemia reperfusion

Xanthine oxidoreductase (XOR) may produce reactive oxygen species and play a role in ischemia-reperfusion injury. Because tissue iron levels increase after ischemia, and because XOR contains functionally critical iron-sulfur clusters, we studied the effects of intracellular iron on XOR expression. Ferric ammonium citrate and FeS[O.sub.4] elevated intracellular iron levels and increased XOR activity up to twofold in mouse fibroblast and human bronchial epithelial cells. Iron increased XOR protein and mRNA levels, whereas protein and RNA synthesis inhibitors abolished the induction of XOR activity. A human XOR promoter construct (nucleotides +42 to--1937) was not induced by iron in human embryonic kidney cells. Hydroxyl radical scavengers did not block induction of XOR activity by iron. Iron chelation by deferoxamine (DFO) decreased XOR activity but did not lower endogenous XOR protein or mRNA levels. Furthermore, DFO reduced the activity of overexpressed human XOR but not the amount of immunoreactive protein. Our data show that XOR activity is transcriptionally induced by iron but post-translationally inactivated by iron chelation. deferoxamine; gene regulation; iron-sulfur proteins; reactive oxygen species; ischemia-reperfusion injury

Recent findings of the nerve growth factor (NGF) calls for a change in major concepts about this prototypical neurotrophic factor. Using X-ray diffraction analysis, its three-dimensional structure was obtained at a 2.3 Angstrom-resolution. It features a new protein fold that is beta-strand-rich and apparently unrelated to the insulin family. The factor has been found to use the trk proto-oncogene product, which has a tyrosine kinase acting as a receptor. In addition, NGF was found to share homologous sequences with brain-derived neurotrophic factor and neurotrophin-3, -4 and -5.