Variations in Methodological Approaches to Measuring Health Inequalities and Inequities: A Scoping Review of Acute Stroke Pathways.

Background: There are a lot of advances that may affect the way treatment is delivered prehospital, including mobile stroke units and point-of-care diagnostics. These have the potential to affect populations differently and therefore affect the distribution of health outcomes.

Objectives: We aimed to address the following research questions: (1) Which geographic and socioeconomic inequalities have been included when evaluating access to acute stroke treatment (including reperfusion therapies)? (2) How have the identified measures been considered/assessed/calculated? (3) We also report any methodological approaches that have been proposed that might further improve the way in which acute stroke care interventions are analysed, specified relating to inequalities.

Improving local authority financial support services for users with complex health needs: a mixed-method economic evaluation of Social Navigators in South Tyneside, UK.

Despite social prescribing being promoted by the UK government for the last decade, the evidence supporting social prescribing remains weak and has mainly been confined to clinical contexts. Our study aimed to evaluate the impact of a Social Navigator (SN) service in South Tyneside on the health and well-being of users who experience financial hardship with complex health needs and limited access to mental health services.Using a mixed-methods design combining secondary analysis of service data (n=330), qualitative interviews with service users (n=15) conducted by peer researchers, and a social return On investment analysis that matched service data with health economic indicators from the UK Social Value Bank.

Current and future perspectives for structural biology at the Grenoble EPN campus: a comprehensive overview.

The European Photon and Neutron campus in Grenoble is a unique site, encompassing the European Synchrotron Radiation Facility Extremely Brilliant Source, the Institut Laue-Langevin, the European Molecular Biology Laboratory and the Institut de Biologie Structurale. Here, we present an overview of the structural biology beamlines, instruments and support facilities available on the EPN campus. These include advanced macromolecular crystallography using neutrons or X-rays, small-angle X-ray or neutron scattering, cryogenic electron microscopy, and spectroscopy.

Exploring the adoption of diaphragm and lung ultrasound (DLUS) by physiotherapists, physical therapists, and respiratory therapists: an updated scoping review.

Background: The adoption of diaphragm and lung ultrasound (DLUS) by physiotherapists, physical therapists, and respiratory therapists ("therapists") to examine and assess the diaphragm and lungs continues to grow. The aim of this updated scoping review is to re-explore and re-collate the evidence around the adoption of DLUS by therapists.

Methods: This scoping review followed the PRISMA-ScR guidelines.

Longitudinal health-related quality of life in people with thoracic aortic aneurysms.

Background: Surgical intervention for thoracic aortic aneurysms is high risk. Understanding changes in health-related quality of life before and after endovascular stent grafting and open surgical repair can aid treatment decision-making.

Methods: The Effective Treatments for Thoracic Aortic Aneurysms ('ETTAA') study (ISRCTN04044627) was a longitudinal, observational study.

A lifetime economic model of mortality and secondary care use for patients discharged from hospital following acute stroke.

Background: The long-term health-economic consequences of acute stroke are typically extrapolated from short-term outcomes observed in different studies, using models based on assumptions about longer-term morbidity and mortality. Inconsistency in these assumptions and the methods of extrapolation can create difficulties when comparing estimates of lifetime cost-effectiveness of stroke care interventions.

Aims: To develop a long-term model consisting of a set of equations to estimate the lifetime effects of stroke care interventions to promote consistency in extrapolation of short-term outcomes.

Targeting the conserved active site of splicing machines with specific and selective small molecule modulators.

The self-splicing group II introns are bacterial and organellar ancestors of the nuclear spliceosome and retro-transposable elements of pharmacological and biotechnological importance. Integrating enzymatic, crystallographic, and simulation studies, we demonstrate how these introns recognize small molecules through their conserved active site. These RNA-binding small molecules selectively inhibit the two steps of splicing by adopting distinctive poses at different stages of catalysis, and by preventing crucial active site conformational changes that are essential for splicing progression.

Linking the Autotaxin-LPA Axis to Medicinal Cannabis and the Endocannabinoid System.

Over the past few decades, many current uses for cannabinoids have been described, ranging from controlling epilepsy to neuropathic pain and anxiety treatment. Medicines containing cannabinoids have been approved by both the FDA and the EMA for the control of specific diseases for which there are few alternatives. However, the molecular-level mechanism of action of cannabinoids is still poorly understood.

Bathing Adaptations in the Homes of Older Adults (BATH-OUT-2): study protocol for a randomised controlled trial, economic evaluation and process evaluation.

Background: The onset of disability in bathing is particularly important for older adults as it can be rapidly followed by disability in other daily activities; this may represent a judicious time point for intervention in order to improve health, well-being and associated quality of life. An important environmental and preventative intervention is housing adaptation, but there are often lengthy waiting times for statutory provision. In this randomised controlled trial (RCT), we aim to evaluate the effectiveness and cost-effectiveness of bathing adaptations compared to no adaptations and to explore the factors associated with routine and expedited implementation of bathing adaptations.

Does destination make a difference? Outcomes after a policy change affecting cutoff times for prehospital transport.

Background: Facilitating primary triage and care at pediatric trauma centers (PTCs) can improve outcomes for children after trauma. However, scene location and regional emergency medical services regulations may result in initial evaluation occurring at nonpediatric facilities with later transportation to PTCs for definitive care. In this study, we assessed the results of a change in transport time cutoff from 30 to 45 minutes on pediatric patient outcomes.

Costs of endovascular and open repair of thoracic aortic aneurysms.

Background: Repair of thoracic aortic aneurysms with either endovascular repair (TEVAR) or open surgical repair (OSR) represents major surgery, is costly and associated with significant complications. The aim of this study was to establish accurate costs of delivering TEVAR and OSR in a cohort of UK NHS patients suitable for open and endovascular treatment for the whole treatment pathway from admission and to discharge and 12-month follow-up.

Methods: A prospective study of UK NHS patients from 30 NHS vascular/cardiothoracic units in England aged ≥18, with distal arch/descending thoracic aortic aneurysms (CTAA) was undertaken.

The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination.

The Mitochondrial Complex I Assembly (MCIA) complex is essential for the biogenesis of respiratory Complex I (CI), the first enzyme in the respiratory chain, which has been linked to Alzheimer's disease (AD) pathogenesis. However, how MCIA facilitates CI assembly, and how it is linked with AD pathogenesis, is poorly understood. Here we report the structural basis of the complex formation between the MCIA subunits ECSIT and ACAD9.

Discovery of potent chromone-based autotaxin inhibitors inspired by cannabinoids.

Autotaxin (ATX) is an enzyme primarily known for the production of lysophosphatidic acid. Being involved in the development of major human diseases, such as cancer and neurodegenerative diseases, the enzyme has been featured in multiple studies as a pharmacological target. We previously found that the cannabinoid tetrahydrocannabinol (THC) could bind and act as an excellent inhibitor of ATX.

Robotic and laparoscopic gynaecological surgery: a prospective multicentre observational cohort study and economic evaluation in England.

Objective: To compare the health-related quality of life and cost-effectiveness of robot-assisted laparoscopic surgery (RALS) versus conventional 'straight stick' laparoscopic surgery (CLS) in women undergoing hysterectomy as part of their treatment for either suspected or proven gynaecological malignancy.

Design: Multicentre prospective observational cohort study.

Setting: Patients aged 16+ undergoing hysterectomy as part of their treatment for gynaecological malignancy at 12 National Health Service (NHS) cancer units and centres in England between August 2017 and February 2020.

Linking medicinal cannabis to autotaxin-lysophosphatidic acid signaling.

Autotaxin is primarily known for the formation of lysophosphatidic acid (LPA) from lysophosphatidylcholine. LPA is an important signaling phospholipid that can bind to six G protein-coupled receptors (LPA). The ATX-LPA signaling axis is a critical component in many physiological and pathophysiological conditions.

BioSAXS at European Synchrotron Radiation Facility - Extremely Brilliant Source: BM29 with an upgraded source, detector, robot, sample environment, data collection and analysis software.

As part of its Extremely Brilliant Source (EBS) upgrade project, the ESRF's BM29 BioSAXS beamline was subject to a significant upgrade and refurbishment. In addition to the replacement of the beamline's original bending magnet source by a two-pole wiggler, leading to an increase in brilliance by a factor of 60, the sample environment of the beamline was almost completely refurbished: a vacuum-compatible Pilatus3 X 2M with a sensitive area of 253.7 mm × 288 mm and frame rates up to 250 Hz was installed, increasing the active area available and thus the q-scaling of scattering images taken; the sample changer was replaced with an upgraded version, allowing more space for customizable sample environments and the installation of two new sample exposure units; the software associated with the beamline was also renewed.

The crystal structure of the EspB-EspK virulence factor-chaperone complex suggests an additional type VII secretion mechanism in Mycobacterium tuberculosis.

Pathogenic species from the Mycobacterium genus are responsible for a number of adverse health conditions in humans and animals that threaten health security and the economy worldwide. Mycobacteria have up to five specialized secretion systems (ESX-1 to ESX-5) that transport virulence factors across their complex cell envelope to facilitate manipulation of their environment. In pathogenic species, these virulence factors influence the immune system's response and are responsible for membrane disruption and contributing to cell death.

Evaluating the Use of Digital Biomarkers to Test Treatment Effects on Cognition and Movement in Patients with Lewy Body Dementia.

Background: PRESENCE was a Phase 2 trial assessing mevidalen for symptomatic treatment of Lewy body dementia (LBD). Participants received daily doses (10, 30, or 75 mg) of mevidalen (LY3154207) or placebo for 12 weeks.

Objective: To evaluate if frequent cognitive and motor tests using an iPad app and wrist-worn actigraphy to track activity and sleep could detect mevidalen treatment effects in LBD.

The impact of a digital joint school educational programme on post-operative outcomes following lower limb arthroplasty: a retrospective comparative cohort study.

Background: As part of an ongoing service improvement project, a digital 'joint school' (DJS) was developed to provide education and support to patients undergoing total hip (THR) and total knee (TKR) replacement surgery. The DJS allowed patients to access personalised care plans and educational resources using web-enabled devices, from being listed for surgery until 12 months post-operation. The aim of this study was to compare a cohort of patients enrolled into the DJS with a cohort of patients from the same NHS trust who received a standard 'non-digital' package of education and support in terms of Health-Related Quality of Life (HRQoL), functional outcomes and hospital length of stay (LoS).

Biallelic pathogenic variants in roundabout guidance receptor 1 associate with syndromic congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent the most common cause of chronic kidney failure in children. Despite growing knowledge of the genetic causes of CAKUT, the majority of cases remain etiologically unsolved. Genetic alterations in roundabout guidance receptor 1 (ROBO1) have been associated with neuronal and cardiac developmental defects in living individuals.

Endovascular stent grafting and open surgical replacement for chronic thoracic aortic aneurysms: a systematic review and prospective cohort study.

Background: The management of chronic thoracic aortic aneurysms includes conservative management, watchful waiting, endovascular stent grafting and open surgical replacement. The Effective Treatments for Thoracic Aortic Aneurysms (ETTAA) study investigates timing and intervention choice.

Objective: To describe pre- and post-intervention management of and outcomes for chronic thoracic aortic aneurysms.

The Dopamine D1 Receptor Positive Allosteric Modulator Mevidalen (LY3154207) Enhances Wakefulness in the Humanized D1 Mouse and in Sleep-Deprived Healthy Male Volunteers.

Dopamine (DA) plays a key role in several central functions including cognition, motor activity, and wakefulness. Although efforts to develop dopamine receptor 1 (D1) agonists have been challenging, a positive allosteric modulator represents an attractive approach with potential better drug-like properties. Our previous study demonstrated an acceptable safety and tolerability profile of the dopamine receptor 1 positive allosteric modulator (D1PAM) mevidalen (LY3154207) in single and multiple ascending dose studies in healthy volunteers (Wilbraham et al.

Aneurysm growth, survival, and quality of life in untreated thoracic aortic aneurysms: the effective treatments for thoracic aortic aneurysms study.

Aims: To observe, describe, and evaluate management and timing of intervention for patients with untreated thoracic aortic aneurysms.

Methods And Results: Prospective study of UK National Health Service (NHS) patients aged ≥18 years, with new/existing arch or descending thoracic aortic aneurysms of ≥4 cm diameter, followed up until death, intervention, withdrawal, or July 2019. Outcomes were aneurysm growth, survival, quality of life (using the EQ-5D-5L utility index), and hospital admissions.