Ketogenic diet modifies ribosomal protein dysregulation in KMT2D Kabuki syndrome.

Background: Kabuki syndrome (KS) is a genetic disorder caused by DNA mutations in KMT2D, a lysine methyltransferase that methylates histones and other proteins, and therefore modifies chromatin structure and subsequent gene expression. Ketones, derived from the ketogenic diet, are histone deacetylase inhibitors that can 'open' chromatin and encourage gene expression. Preclinical studies have shown that the ketogenic diet rescues hippocampal memory neurogenesis in mice with KS via the epigenetic effects of ketones.

Cognitive Functioning and Psychosocial Outcomes in Adults with Complex Congenital Heart Disease: A Cross-sectional Pilot Study.

Adults with complex congenital heart disease (CHD) are at risk for cognitive dysfunction. However, associations between cognitive dysfunction and psychosocial outcomes are poorly defined. Between June and November 2022, we prospectively recruited 39 adults with complex CHD who completed a computerized cognitive assessment (Cogstate) and validated psychosocial scales measuring psychological distress, health-related quality of life (HRQOL), and resilience.

Corticosteroids to safely reduce neonatal respiratory morbidity after late preterm and term planned caesarean section birth? A randomised placebo-controlled feasibility study.

Objectives: To assess the feasibility of conducting a randomised placebo-controlled trial of corticosteroids prior to planned caesarean section from 35 to 39 weeks.

Design: A triple-blind, placebo-controlled, parallel, trial randomised at the participant level (1:1 ratio). Additional feasibility data obtained by questionnaires from trial participants and women who declined trial participation, and focus groups with local site researchers and clinicians.

Community workshops increase advance care planning knowledge, appointment of legal proxies and completion of end-of life written plans.

Advance Care Planning involves having conversations, completing documents detailing individuals' end-of life treatment and care preferences, and appointing legal proxies who make health, lifestyle, or financial decisions. Although beneficial outcomes have been demonstrated, community rates of Advance Care Planning remain low. We developed a theoretically based workshop to increase knowledge and change behaviors in relation to Advance Care Planning; 347 participants completed the workshop.

FeMV is a cathepsin-dependent unique morbillivirus infecting the kidneys of domestic cats.

Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the family. We determined the complete sequence of FeMV directly from an FeMV-positive urine sample without virus isolation or cell passage. Sequence analysis of the viral genome revealed potential divergence from characteristics of archetypal morbilliviruses.

COVID-19 in New South Wales children during 2021: severity and clinical spectrum.

Objectives: To describe the severity and clinical spectrum of coronavirus disease 2019 (COVID-19) in children during the 2021 New South Wales outbreak of the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Design, Setting: Prospective cohort study in three metropolitan Sydney local health districts, 1 June - 31 October 2021.

Participants: Children under 16 years of age with positive SARS-CoV-2 nucleic acid test results admitted to hospital or managed by the Sydney Children's Hospital Network (SCHN) virtual care team.

Program for the Education and Enrichment of Relational Skills for adolescents with an acquired brain injury: A randomized controlled trial.

Aim: To test the efficacy of a group social skills intervention on social functioning in adolescents with a brain injury.

Method: Thirty-six adolescents (mean age 14y, SD 1y 8mo, age range 12y 1mo-16y 3mo; 17 females) with acquired brain injury (ABI; ≥12mo postintervention; n=19) or cerebral palsy (n=17) were randomly allocated to the Program for the Education in Enrichment of Relational Skills (PEERS) or usual care. The primary outcome was the Social Skills Improvement System-Rating Scales (SSIS-RS).

Coastal dunes as a sink and secondary source of marine plastics: A study at Perran Beach, southwest England.

Plastic food packaging and containers (n = 263) have been retrieved from the scarped foredunes at Perran Beach, SW England, following a storm surge. Samples displayed evidence of cracking, scratching, discolouration, staining and hydroxyl and carbonyl stretching, but legible text indicating their origin, dates of manufacture/expiration, packaging codes and logos, coupled with online product searches, allowed 25 food packets and 87 containers to be aged. Estimates of food packaging age spanned a 43-year period (1975-2018), with a median age of 25 years, while estimates for containers spanned 57 years (1962-2019), with a median age of 19 years.

In Pursuit of an Allosteric Human Tropomyosin Kinase A (TrkA) Inhibitor for Chronic Pain.

Human β-nerve growth factor (β-NGF) and its associated receptor, human tropomyosin receptor kinase A (TrkA), have been demonstrated to be key factors in the perception of pain. However, efficacious small molecule therapies targeting the intracellularly located TrkA kinase have not been explored thoroughly for pain management. Herein, we report the pharmacological properties of a selective TrkA allosteric inhibitor, .

Reflections from the forgotten frontline: 'The reality for children and staff in residential care' during COVID-19.

Currently, 78,150 children are in care in England, with 11% of the most vulnerable living in 2,460 residential homes due to multitype traumas. These children require safe and secure trauma-informed therapeutic care. However, the children's residential care workforce delivering this vital care is an unrepresented, under-researched and largely unsupported professional group.

Transport, weathering and pollution of plastic from container losses at sea: Observations from a spillage of inkjet cartridges in the North Atlantic Ocean.

Observations of beached polypropylene inkjet cartridges, spilled from a ship container lost in the North Atlantic Ocean, have been compiled through calls on international social media. Within a period of four years from the spillage, a total of about 1500 cartridges was reported in locations as far apart as Florida and northern Norway. The distribution of cartridges reflected the principal surface currents in the ocean, with some carried by the Azores and Canary currents around the North Atlantic Gyre, and others transported northwards with the North Atlantic and Norwegian currents.

Synthetic inhibitor leads of human tropomyosin receptor kinase A (TrkA).

virtual screening followed by biochemical, biophysical, and cellular screening resulted in the identification of distinctly different TrkA kinase domain inhibitor scaffolds. X-ray structural analysis of representative inhibitors bound to TrkA kinase domain defined the binding mode and rationalized the mechanism of action. Preliminary assessment of the sub-type selectivity against the closest TrkB isoform, and early ADME guided the progression of select inhibitor leads in the screening cascade.

The Effects of Extended-Release Stimulant Medication on Sleep in Children with ADHD.

Objective: Although stimulant medications, such as methylphenidate hydrochloride (MPH), are effective at reducing the core symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), they may also disrupt children's sleep. This study aimed to investigate the acute impact of extended-release MPH on sleep using both actigraphy and polysomnography (PSG).

Method: Participants were 26 medication-naïve newly and rigorously diagnosed children with ADHD (23 males; 3 females) with a mean age of 8 years, 8 months ( = 24.

Weathering and persistence of plastic in the marine environment: Lessons from LEGO.

The residence times of plastics in the oceans are unknown, largely because of the durability of the material and the relatively short (decadal) period of time over which plastic products have been manufactured. In this study, classic LEGO bricks constructed of acrylonitrile butadiene styrene (ABS) and washed up on beaches of southwest England have been subjected to X-ray fluorescence (XRF) analysis and the spectra and any other identifiers matched with unweathered blocks stored in collections or sets of known history. Relative to unweathered equivalents, weathered blocks exhibit varying degrees of yellowing, fracturing and fouling, and are of lower mass, average stud height and mechanical strength.