Hospice topophilia and topophobia as experienced by a local population: Implications for equity of access.

The examination of hospice settings from the position of space and place is an emerging area of academic interest. Engaging with this perspective, this paper explores how topophilia and topophobia of the physical hospice setting coincides with and informs a broader love and fear of hospice care and UK hospice organisations. We report the findings of a qualitative study of 53 participants in the catchment population of a hospice in England.

The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria.

Argininosuccinate lyase (ASL) is integral to the urea cycle detoxifying neurotoxic ammonia and the nitric oxide (NO) biosynthesis cycle. Inherited ASL deficiency causes argininosuccinic aciduria (ASA), a rare disease with hyperammonemia and NO deficiency. Patients present with developmental delay, epilepsy and movement disorder, associated with NO-mediated downregulation of central catecholamine biosynthesis.

Improving asthma care through implementation of the SENTINEL programme: findings from the pilot site.

Aim: Short-acting β-agonist (SABA) overuse adversely impacts asthma-related outcomes and the environment. The SABA rEductioN Through ImplemeNting Hull asthma guidELines (SENTINEL) programme aims to reduce SABA overuse through supported implementation of an adult asthma guideline, which advocates for a SABA-free maintenance and reliever therapy (MART)-preferred treatment where appropriate, across six primary care networks (PCNs) in the UK. We present findings on patient/disease characteristics, asthma prescribing patterns and exacerbation rates from the pilot PCN.

Calculating worldwide needs for morphine for pain in advanced cancer and proportions feasibly met by country estimates of requirements and consumption. Retrospective, time-series analysis (1997-2017).

Lack of access to therapeutic opioids continuing causes global health inequalities. Access to morphine for symptom control is regulated under the terms of the Single Convention on Narcotics, countries must submit annual morphine requirement estimates and report consumption to the International Narcotics Control Board (INCB). INCB indicates access to morphine is increasing, however, estimated needs are unreported so changing proportions of needs feasibly met by requirements and consumption are unknown.

Atypical Guillain-Barré syndrome presenting with fluctuating weakness.

Guillain-Barré Syndrome (GBS) is an immune-mediated polyneuropathy, most often occurring within weeks of an infection. Cases of COVID-19-related GBS have been reported, and the typical presentation is a progressive ascending paralysis. We describe a case of a 40-year-old with recent symptomatic COVID-19 who presented with atypical GBS findings, hand weakness that progressed to tetraplegia within 24 hours.

Metabolomics analysis of antiquitin deficiency in cultured human cells and plasma: Relevance to pyridoxine-dependent epilepsy.

Deficiency of antiquitin (α-aminoadipic semialdehyde dehydrogenase), an enzyme involved in lysine degradation and encoded by ALDH7A1, is the major cause of vitamin B -dependent epilepsy (PDE-ALDH7A1). Despite seizure control with high dose pyridoxine (PN), developmental delay still occurs in approximately 70% of patients. We aimed to investigate metabolic perturbations due to possible previously unidentified roles of antiquitin, which may contribute to developmental delay, as well as metabolic effects of high dose pyridoxine supplementation reflecting the high doses used for seizure control in patients with PDE-ALDH7A1.

Faculty Development and Infrastructure to Support Educational Scholarship: A Scoping Review on Author Development.

Purpose: Medical educators are expected to produce educational scholarship, which can lead to career advancement and promotion. Institutions have developed author development programs, which vary in duration, instructional approach, and effectiveness. However, no summation of the evidence exists for academic medicine leaders to use as guidance for building similar programs.

Cln5 represents a new type of cysteine-based -depalmitoylase linked to neurodegeneration.

Genetic variants are associated with childhood neurodegeneration and Alzheimer's disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (-depalmitoylation) activity using fluorescent substrates.

Towards codesign in respiratory care: development of an implementation-ready intervention to improve guideline-adherent adult asthma care across primary and secondary care settings (The SENTINEL Project).

Short-acting beta agonist (SABA) overuse (≥3 canisters annually) is associated with worse asthma outcomes and accounts for the majority of greenhouse gas emissions from asthma inhalers in England. Reducing SABA overuse aligns with the National Health Service long-term plan to optimise asthma treatment while minimising environmental impact, but adoption of local asthma guidelines for a SABA-free maintenance and reliever therapy strategy for step 3 asthma patients is limited. In this we describe patient and staff involvement in a codesign process adapted from experience-based codesign (EBCD) principles to develop an implementation-ready intervention within a practice-relevant timescale.

No severe genetic bottleneck in a rapidly range-expanding bumblebee pollinator.

Genetic bottlenecks can limit the success of populations colonizing new ranges. However, successful colonizations can occur despite bottlenecks, a phenomenon known as the genetic paradox of invasion. Eusocial Hymenoptera such as bumblebees ( spp.

Distal and proximal hypoxia response elements cooperate to regulate organ-specific erythropoietin gene expression.

While it is well-established that distal hypoxia response elements (HREs) regulate hypoxia-inducible factor (HIF) target genes such as erythropoietin (Epo), an interplay between multiple distal and proximal (promoter) HREs has not been described so far. Hepatic Epo expression is regulated by a HRE located downstream of the EPO gene, but this 3' HRE is dispensable for renal EPO gene expression. We previously identified a 5' HRE and could show that both HREs direct exogenous reporter gene expression.

Mindfulness for undergraduate health and social care professional students: Findings from a qualitative scoping review using the 3P model.

Context: With many health and social care schools offering mindfulness training (MT) there is a need for deeper understanding about pedagogical issues. Despite encouraging findings showing relationships between MT and student stress reduction, there is little qualitative synthesis of the literature about best principles for teaching and learning.

Methods: We report on a qualitative scoping review using the stages of Arksey and O'Malley's framework.

Spatial ecology of a range-expanding bumble bee pollinator.

Molecular methods have greatly increased our understanding of the previously cryptic spatial ecology of bumble bees ( spp.), with knowledge of the spatial ecology of these bees being central to conserving their essential pollination services. the Tree Bumble Bee, is unusual in that it has recently rapidly expanded its range, having colonized much of the UK mainland since 2001.

New insights into human lysine degradation pathways with relevance to pyridoxine-dependent epilepsy due to antiquitin deficiency.

Deficiency of antiquitin (ATQ), an enzyme involved in lysine degradation, is the major cause of vitamin B -dependent epilepsy. Accumulation of the potentially neurotoxic α-aminoadipic semialdehyde (AASA) may contribute to frequently associated developmental delay. AASA is formed by α-aminoadipic semialdehyde synthase (AASS) via the saccharopine pathway of lysine degradation, or, as has been postulated, by the pipecolic acid (PA) pathway, and then converted to α-aminoadipic acid by ATQ.

Queen Longevity and Fecundity Affect Conflict with Workers over Resource Inheritance in a Social Insect.

Resource inheritance is a major source of conflict in animal societies. However, the assumptions and predictions of models of conflict over resource inheritance have not been systematically tested within a single system. We developed an inclusive fitness model for annual eusocial Hymenoptera that predicts a zone of conflict in which future reproductive workers are selected to enforce nest inheritance before the queen is selected to cede the nest.

The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study.

Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic encephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients.

Generation of renal Epo-producing cell lines by conditional gene tagging reveals rapid HIF-2 driven Epo kinetics, cell autonomous feedback regulation, and a telocyte phenotype.

Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycythaemia and anaemia. To overcome this limitation, we have generated a novel transgenic mouse model expressing Cre recombinase specifically in the active fraction of renal Epo-producing (REP) cells.

A quantitative method for evaluating cortical responses to electrical stimulation.

Background: Electrical stimulation of the cortex using subdurally implanted electrodes can causally reveal structural connectivity by eliciting cortico-cortical evoked potentials (CCEPs). While many studies have demonstrated the potential value of CCEPs, the methods to evaluate them were often relatively subjective, did not consider potential artifacts, and did not lend themselves to systematic scientific investigations.

New Method: We developed an automated and quantitative method called SIGNI (Stimulation-Induced Gamma-based Network Identification) to evaluate cortical population-level responses to electrical stimulation that minimizes the impact of electrical artifacts.

Normal serum protein electrophoresis and mutated IGHV genes detect very slowly evolving chronic lymphocytic leukemia patients.

More than 35 years after the Binet classification, there is still a need for simple prognostic markers in chronic lymphocytic leukemia (CLL). Here, we studied the treatment-free survival (TFS) impact of normal serum protein electrophoresis (SPE) at diagnosis. One hundred twelve patients with CLL were analyzed.

Multiomics tools for the diagnosis and treatment of rare neurological disease.

Conventional workup of rare neurological disease is frequently hampered by diagnostic delay or lack of diagnosis. While biomarkers have been established for many neurometabolic disorders, improved methods are required for diagnosis of previously unidentified or underreported causes of rare neurological disease. This would result in a higher diagnostic yield and increased patient numbers required for interventional studies.

Plasma metabolomics reveals a diagnostic metabolic fingerprint for mitochondrial aconitase (ACO2) deficiency.

Mitochondrial respiratory chain dysfunction has been identified in a number of neurodegenerative disorders. Infantile cerebellar-retinal degeneration associated with mutations in the mitochondrial aconitase 2 gene (ACO2) has been recently described as a neurodegenerative disease of autosomal recessive inheritance. To date there is no biomarker for ACO2 deficiency and diagnosis relies on genetic analysis.

Confirmation of mutations in as a novel cause of vitamin B -dependent epilepsy.

Vitamin-B-dependent epilepsies are a heterogenous group of treatable disorders due to mutations in several genes ( or ). In neonatal seizures, defects in explain a major fraction of cases. Very recently biallelic mutations in were shown to be a novel cause in five families.

Does systemic administration of casein phosphopeptides affect orthodontic movement and root resorption in rats?

Objectives: To assess the potential effects of casein phosphopeptides (CPPs) on orthodontically induced iatrogenic root resorption (OIIRR) and orthodontic teeth movement.

Materials And Methods: Forty Wistar rats (aged 11 weeks) were randomly divided into experimental group (EG; n = 20) that received a diet supplemented with CPP and control group (CG; n = 20) devoid of diet supplement. A 150 g force was applied using nickel titanium (NiTi) coil that was bonded on maxillary incisors and extended unilaterally to a maxillary first molar.