Treatment of Hypothalamic Obesity With GLP-1 Analogs.

Introduction: Congenital and acquired damage to hypothalamic nuclei or neuronal circuits controlling satiety and energy expenditure results in hypothalamic obesity (HO). To date, successful weight loss and satiety has only been achieved in a limited number of affected patients across multiple drug trials. Glucagon-like peptide-1 (GLP-1) acts via central pathways that are independent from the hypothalamus to induce satiety.

Opportunities for digitally-enabled personalization and decision support for pediatric growth hormone therapy.

Smart technologies and connected health are providing opportunities for improved healthcare for chronic conditions. Acceptance by healthcare professionals (HCPs) and patients is crucial for successful implementation. Evidence-based standards, technological infrastructure and regulatory processes are needed to integrate digital tools into clinical practice.

Children and young people's preferences and needs when using health technology to self-manage a long-term condition: a scoping review.

Background: The use of patient-facing health technologies to manage long-term conditions (LTCs) is increasing; however, children and young people (CYP) may have preferences about health technologies which they interact or engage with, that influence their decision to use these technologies.

Aims: To identify CYP's reported preferences about health technologies to self-manage LTCs.

Methods: We undertook a scoping review, searching MEDLINE, PsycINFO and CINAHL in July 2021.

Artificial intelligence in paediatric endocrinology: conflict or cooperation.

Artificial intelligence (AI) in medicine is transforming healthcare by automating system tasks, assisting in diagnostics, predicting patient outcomes and personalising patient care, founded on the ability to analyse vast datasets. In paediatric endocrinology, AI has been developed for diabetes, for insulin dose adjustment, detection of hypoglycaemia and retinopathy screening; bone age assessment and thyroid nodule screening; the identification of growth disorders; the diagnosis of precocious puberty; and the use of facial recognition algorithms in conditions such as Cushing syndrome, acromegaly, congenital adrenal hyperplasia and Turner syndrome. AI can also predict those most at risk from childhood obesity by stratifying future interventions to modify lifestyle.

Unconventional roles of chromatin remodelers and long non-coding RNAs in cell division.

The aim of this review article is to focus on the unconventional roles of epigenetic players (chromatin remodelers and long non-coding RNAs) in cell division, beyond their well-characterized functions in chromatin regulation during cell differentiation and development. In the last two  decades, diverse experimental evidence has shown that subunits of SRCAP and p400/TIP60 chromatin remodeling complexes in humans relocate from interphase nuclei to centrosomes, spindle or midbody, with their depletion yielding an array of aberrant outcomes of mitosis and cytokinesis. Remarkably, this behavior is shared by orthologous subunits of the Drosophila melanogaster DOM/TIP60 complex, despite fruit flies and humans diverged over 700 million years ago.

Evaluating the Usefulness and Ease of Use of a Next-Generation-Connected Drug Delivery Device for Growth Hormone Therapy: Qualitative Study of Health Care Professionals' Perceptions.

Background: Digital solutions targeting children's health have become an increasingly important element in the provision of integrated health care. For the treatment of growth hormone deficiency (GHD), a unique connected device is available to facilitate the delivery of recombinant human growth hormone (r-hGH) by automating the daily injection process and collecting injection data such that accurate adherence information is available to health care professionals (HCPs), caregivers, and patients. The adoption of such digital solutions requires a good understanding of the perspectives of HCPs as key stakeholders because they leverage data collection and prescribe these solutions to their patients.

Knockdown of DOM/Tip60 Complex Subunits Impairs Male Meiosis of .

ATP-dependent chromatin remodeling complexes are involved in nucleosome sliding and eviction and/or the incorporation of histone variants into chromatin to facilitate several cellular and biological processes, including DNA transcription, replication and repair. The DOM/TIP60 chromatin remodeling complex of contains 18 subunits, including the DOMINO (DOM), an ATPase that catalyzes the exchange of the canonical H2A with its variant (H2A.V), and TIP60, a lysine-acetyltransferase that acetylates H4, H2A and H2A.

Supportive use of digital technologies during transition to adult healthcare for young people with long-term conditions, focusing on Type 1 diabetes mellitus: A scoping review.

Type 1 diabetes mellitus (T1DM) is the second most common chronic or long-term condition (LTC) affecting young people (YP); when transitioning from paediatric to adult healthcare, young people with LTCs such as T1DM are expected to self-manage medication, diet and clinical appointments. This scoping review aimed to analyse research examining ways digital health technologies were used to support YP with LTCs during transition from paediatric to adult healthcare and to establish YP's needs, experiences and challenges when transitioning. We aimed to identify knowledge gaps and inform development of a novel chatbot with components such as avatars and linked videos to help YP with T1DM gain self-management confidence and competence during transition.

Accelerating digital health literacy for the treatment of growth disorders: The impact of a massive open online course.

Background: Growth hormone deficiency (GHD) is a rare disorder characterized by inadequate secretion of growth hormone (GH) from the anterior pituitary gland. One of the challenges in optimizing GH therapy is improving adherence. Using digital interventions may overcome barriers to optimum treatment delivery.

Playing your pain away: designing a virtual reality physical therapy for children with upper limb motor impairment.

Children with upper limb motor impairment often undergo repetitive therapeutic physiotherapy sessions to minimize functional disabilities of the affected area. Even though therapeutic processes can improve functional outcomes and minimize persistent disabilities, patients often neglect to participate fully in physical therapies due to the associated procedural pain. Over recent decades, there has been a growing interest in designing non-pharmacological interventions which aim to minimize pain during physical therapies and improve functional outcomes.

Precision diagnostics in children.

Medical practice is transforming from a reactive to a pro-active and preventive discipline that is underpinned by precision medicine. The advances in technologies in such fields as genomics, proteomics, metabolomics, transcriptomics and artificial intelligence have resulted in a paradigm shift in our understanding of specific diseases in childhood, greatly enhanced by our ability to combine data from changes within cells to the impact of environmental and population changes. Diseases in children have been reclassified as we understand more about their genomic origin and their evolution.

Home-based immersive virtual reality physical rehabilitation in paediatric patients for upper limb motor impairment: a feasibility study.

Upper limb motor impairment (ULMI) rehabilitation is a long-term, demanding and challenging process to recover motor functionality. Children and adolescents may be limited in daily life activities due to reduced functions such as decreased joint movement or muscle weakness. Home-based therapy with Immersive Virtual Reality can offer greater accessibility, delivery and early rehabilitation to significantly optimise functional outcomes and quality of life.

Epigenetic Silencing of P-Element Reporter Genes Induced by Transcriptionally Active Domains of Constitutive Heterochromatin in .

Reporter genes inserted via P-element integration into different locations of the genome have been routinely used to monitor the functional state of chromatin domains. It is commonly thought that P-element-derived reporter genes are subjected to position effect variegation (PEV) when transposed into constitutive heterochromatin because they acquire heterochromatin-like epigenetic modifications that promote silencing. However, sequencing and annotation of the genome have shown that constitutive heterochromatin is a genetically and molecularly heterogeneous compartment.

The Green Valley of Constitutive Heterochromatin: Protein-Coding Genes Involved in Cell Division Control.

Constitutive heterochromatin represents a significant fraction of eukaryotic genomes (10% in Arabidopsis, 20% in humans, 30% in , and up to 85% in certain nematodes) and shares similar genetic and molecular properties in animal and plant species. Studies conducted over the last few years on and other organisms led to the discovery of several functions associated with constitutive heterochromatin. This made it possible to revise the concept that this ubiquitous genomic territory is incompatible with gene expression.

Evolutionary conserved relocation of chromatin remodeling complexes to the mitotic apparatus.

Background: ATP-dependent chromatin remodeling complexes are multi-protein machines highly conserved across eukaryotic genomes. They control sliding and displacing of the nucleosomes, modulating histone-DNA interactions and making nucleosomal DNA more accessible to specific binding proteins during replication, transcription, and DNA repair, which are processes involved in cell division. The SRCAP and p400/Tip60 chromatin remodeling complexes in humans and the related Drosophila Tip60 complex belong to the evolutionary conserved INO80 family, whose main function is promoting the exchange of canonical histone H2A with the histone variant H2A in different eukaryotic species.

Meaningful involvement of children and young people in health technology development.

The anatomical, physiological, and developmental changes which arise as children mature through childhood and adolescence support the need to develop new health technologies that meet the specific requirements of children and young people (CYP). Failing to involve CYP during the development of technology increases the risk that the outcome falls short of their expectations and needs, leading to rejection of novel interventions. Through participation in health technology development, CYP and their families can provide context, insight, personal experience and tacit knowledge to ensure that the end-product is usable, acceptable, and can be integrated into its intended environment.

Managing interorganisational collaborations to develop medical technologies: the contribution of interpersonal relationships.

The development of medical technologies that effectively meet clinical and patient needs increasingly relies upon collaborative working between clinicians, businesses and universities. While this "open" innovation process may provide access to additional resources, knowledge, and expertise the process is not frictionless. At the personal level, individuals may have different ways of working and incentives and at the organisational level, partners may have their own cultures and processes.

Overcoming challenges to develop technology for child health.

Millions of children and young people (CYP) in the UK are affected by chronic or rare health conditions. Rapid advances in science and technology have resulted in CYP with chronic and rare conditions now surviving well into adulthood. New technologies have the potential to improve short- and long-term health outcomes for CYP with health conditions, prevent adult onset disease and complications, and reduce the burden on health services.

Treatment of Acquired Hypothalamic Obesity: Now and the Future.

The hypothalamus is the centre of neuroendocrine regulation of energy homeostasis and appetite. Maldevelopment of, or damage to, the key hypothalamic nuclei disrupts the coordinated balance between energy intake and expenditure leading, to rapid and excessive weight gain. Hypothalamic obesity is compounded by a disruption of the hypothalamic-pituitary axis, sleep disruption, visual compromise, and neurological and vascular sequalae.

Constitutive Heterochromatin in Eukaryotic Genomes: A Mine of Transposable Elements.

Transposable elements (TEs) are abundant components of constitutive heterochromatin of the most diverse evolutionarily distant organisms. TEs enrichment in constitutive heterochromatin was originally described in the model organism , but it is now considered as a general feature of this peculiar portion of the genomes. The phenomenon of TE enrichment in constitutive heterochromatin has been proposed to be the consequence of a progressive accumulation of transposable elements caused by both reduced recombination and lack of functional genes in constitutive heterochromatin.

Medical Device Development for Children and Young People-Reviewing the Challenges and Opportunities.

Development of specific medical devices (MDs) is required to meet the healthcare needs of children and young people (CYP). In this context, MD development should address changes in growth and psychosocial maturation, physiology, and pathophysiology, and avoid inappropriate repurposing of adult technologies. Underpinning the development of MD for CYP is the need to ensure MD safety and effectiveness through pediatric MD-specific regulations.

Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease.

Context: Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD).

Objective: We explored whether rituximab (RTX), a B-lymphocyte-depleting agent, would increase remission rates when administered with a short course of ATD.

Methods: This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism.