Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor.

Inhibition of the mitochondrial deubiquitinating (DUB) enzyme USP30 is neuroprotective and presents therapeutic opportunities for the treatment of idiopathic Parkinson's disease and mitophagy-related disorders. We integrated structural and quantitative proteomics with biochemical assays to decipher the mode of action of covalent USP30 inhibition by a small-molecule containing a cyanopyrrolidine reactive group, . The inhibitor demonstrated high potency and selectivity for endogenous USP30 in neuroblastoma cells.

Public engagement to refine a whole-school intervention to promote adolescent mental health.

Background: Despite high rates of adolescent mental health problems, there are few effective school-based interventions to address this. Whole-school interventions offer a feasible and sustainable means of promoting mental health, but few have to date been evaluated. Previously we trialled the Learning Together intervention comprising local needs assessment, student and staff participation in decision-making, restorative practice, and a social and emotional skills curriculum.

Qualitative study of the feasibility and acceptability of implementation, and potential mechanisms of Learning Together for Mental Health, a whole-school intervention aiming to promote mental health and wellbeing in secondary schools.

Background: Despite high rates of adolescent mental-health problems, there are few effective whole-school interventions to address this. Whole-school interventions offer a feasible and sustainable means of promoting mental health. We previously evaluated the Learning Together (LT) intervention which was effective in preventing bullying (primary outcome), promoting mental well-being, psychological functioning, and reducing substance use (secondary outcomes).

Assessing the evidence for health benefits of low-level weight loss: a systematic review.

Individuals with excess weight are at a higher risk for various physical and mental health conditions. Interventions targeting weight loss can improve health, with modest weight loss of five to ten percent of body weight often considered clinically meaningful for enhancing health outcomes. However, the benefits of achieving low-level weight loss ( < 5% body weight) are poorly understood.

Native mass spectrometry prescreening of G protein-coupled receptor complexes for cryo-EM structure determination.

G protein-coupled receptors (GPCRs) are essential transmembrane proteins playing key roles in human health and disease. Understanding their atomic-level molecular structure and conformational states is imperative for advancing drug development. Recent breakthroughs in single-particle cryogenic electron microscopy (cryo-EM) have propelled the structural biology of GPCRs into a new era.

The Impact of Non-Fiscal Mandatory and Voluntary Policies and Interventions on the Reformulation of Food and Beverage Products: A Systematic Review.

: Low quality diets are a risk factor for non-communicable diseases; therefore, improving diet quality is a public health and policy priority in the UK and elsewhere. Reformulating food/beverage products to make them healthier may be an effective approach. Evidence suggests that fiscal interventions, notably taxes/levies on soft drinks, can lead to reformulation but the evidence for voluntary or mandated non-fiscal interventions is less clear.

Parental migration, socioeconomic deprivation and hospital admissions in preschool children in England: national birth cohort study, 2008 to 2014.

Background: A third of children born in England have at least one parent born outside the United Kingdom (UK), yet family migration history is infrequently studied as a social determinant of child health. We describe rates of hospital admissions in children aged up to 5 years by parental migration and socioeconomic group.

Methods: Birth registrations linked to Hospital Episode Statistics were used to derive a cohort of 4,174,596 children born in state-funded hospitals in England between 2008 and 2014, with follow-up until age 5 years.

The Impact of COVID-19 on Acute Surgeries in England Among the Under-25s: A Retrospective Study of 61,360 Appendicitis and 15,850 Testicular Torsion Admissions.

Background: Little is known about how COVID-19 impacted acute surgical activity for children and young people (CYP) across England. Appendicitis and testicular torsion are common surgical conditions where treatment delays can lead to avoidable complications. We undertook a retrospective national cohort study.

Changing patterns of health risk in adolescence: implications for health policy.

Adolescence is a time of physical, cognitive, social, and emotional development. This period is a very sensitive developmental window; environmental exposures, the development of health behaviours (eg, smoking and physical activity), and illness during adolescence can have implications for lifelong health. In the UK and other high-income countries, the experience of adolescence has changed profoundly over the past 20 years.

Assessing the impact of obesity interventions in the early years: a systematic review of UK-based studies.

Objectives: Childhood obesity rates in the UK are high. The early years of childhood are critical for establishing healthy behaviours and offer interventional opportunities. We aimed to identify studies evaluating the impact of UK-based obesity interventions in early childhood.

The impact of the COVID-19 pandemic on 397 631 elective dental admissions among the under-25s in England: a retrospective study.

Background: COVID-19 caused widespread disruptions to health services worldwide, including reductions in elective surgery. Tooth extractions are among the most common reasons for elective surgery among children and young people (CYP). It is unclear how COVID-19 affected elective dental surgeries in hospitals over multiple pandemic waves at a national level.

Fast and Accurate Disulfide Bridge Detection.

Recombinant expression of proteins, propelled by therapeutic antibodies, has evolved into a multibillion dollar industry. Essential here is the quality control assessment of critical attributes, such as sequence fidelity, proper folding, and posttranslational modifications. Errors can lead to diminished bioactivity and, in the context of therapeutic proteins, an elevated risk for immunogenicity.

Childhood attention-deficit hyperactivity disorder: socioeconomic inequalities in symptoms, impact, diagnosis and medication.

Background: Children from disadvantaged backgrounds are at greater risk of attention-deficit hyperactivity disorder (ADHD)-related symptoms, being diagnosed with ADHD, and being prescribed ADHD medications. We aimed to examine how inequalities manifest across the 'patient journey', from perceptions of impacts of ADHD symptoms on daily life, to the propensity to seek and receive a diagnosis and treatment.

Methods: We investigated four 'stages': (1) symptoms, (2) caregiver perception of impact, (3) diagnosis and (4) medication, in two data sets: UK Millennium Cohort Study (MCS, analytic n ~ 9,000), with relevant (parent-reported) information on all four stages (until 14 years); and a population-wide 'administrative cohort', which includes symptoms (child health checks) and prescriptions (dispensing records), born in Scotland, 2010-2012 (analytic n ~ 100,000), until ~6 years.

Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology.

We present a hydrogen/deuterium exchange workflow coupled to tandem mass spectrometry (HX-MS) that supports the acquisition of peptide fragment ions alongside their peptide precursors. The approach enables true auto-curation of HX data by mining a rich set of deuterated fragments, generated by collisional-induced dissociation (CID), to simultaneously confirm the peptide ID and authenticate MS-based deuteration calculations. The high redundancy provided by the fragments supports a confidence assessment of deuterium calculations using a combinatorial strategy.

Mobile barrier mechanisms for Na-coupled symport in an MFS sugar transporter.

While many 3D structures of cation-coupled transporters have been determined, the mechanistic details governing the obligatory coupling and functional regulations still remain elusive. The bacterial melibiose transporter (MelB) is a prototype of major facilitator superfamily transporters. With a conformation-selective nanobody, we determined a low-sugar affinity inward-facing Na-bound cryoEM structure.

Admissions to paediatric medical wards with a primary mental health diagnosis: a systematic review of the literature.

Objective: To systematically review the literature describing children and young people (CYP) admissions to paediatric general wards because of primary mental health (MH) reasons, particularly in MH crisis.

Design: PubMed, Embase, PsycINFO, Web of Science and Google Scholar were searched, with no restriction on country or language. We addressed five search questions to inform: trends and/or the number of admissions, the risk factors for adverse care, the experiences of CYP, families/carers and healthcare professionals (HCPs) and the evidence of interventions aimed at improving the care during admissions.

Mapping the architecture of the initiating phosphoglycosyl transferase from O-antigen biosynthesis in a liponanoparticle.

Bacterial cell surface glycoconjugates are critical for cell survival and for interactions between bacteria and their hosts. Consequently, the pathways responsible for their biosynthesis have untapped potential as therapeutic targets. The localization of many glycoconjugate biosynthesis enzymes to the membrane represents a significant challenge for expressing, purifying, and characterizing these enzymes.

Impact of the COVID-19 pandemic on the clinical management trends for acute appendicitis among the under-25s: a retrospective study.

Objective: To describe the COVID-19 pandemic's impact on acute appendicitis management on children and young people (CYP).

Design: Retrospective cohort study.

Setting: All English National Health Service hospitals.

Mental Health Admissions to Paediatric Wards Study (MAPS): a protocol for the analysis of Hospital Episode Statistics (HES) data.

Introduction: Children and young people (CYP) presenting with a mental health (MH) crisis are frequently admitted to general acute paediatric wards as a place of safety. Prior to the pandemic, a survey in England showed that CYP occupied 6% of general paediatric inpatient beds due to an MH crisis, and there have been longstanding concerns about the quality of care to support these patients in this setting. Mental Health Admissions to Paediatric Wards Study aims to generate a theory of change (ToC) model to improve the quality of care for CYP admitted to acute paediatric services after presenting in a MH crisis.