Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor.

Kisspeptin receptor (KISS1R), belonging to the class A peptide-GPCR family, plays a key role in the regulation of reproductive physiology after stimulation by kisspeptin and is regarded as an attractive drug target for reproductive diseases. Here, we demonstrated that KISS1R can couple to the G pathway besides the well-known G pathway. We further resolved the cryo-electron microscopy (cryo-EM) structure of KISS1R-G and KISS1R-G complexes bound to the synthetic agonist TAK448 and structure of KISS1R-G complex bound to the endogenous agonist KP54.

The optimal surface for delivery of CPR: An updated systematic review and meta-analysis.

Aim: To determine the effect of CPR delivery surface (e.g. firm mattress, floor, backboard) on patient outcomes and CPR delivery.

Digital Twins of Acute Hypoxemic Respiratory Failure Patients Suggest a Mechanistic Basis for Success and Failure of Noninvasive Ventilation.

Objectives: To clarify the mechanistic basis for the success or failure of noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF).

Design: We created digital twins based on mechanistic computational models of individual patients with AHRF.

Setting: Interdisciplinary Collaboration in Systems Medicine Research Network.

Literature review and meta-analysis of natalizumab therapy for the treatment of highly active relapsing remitting multiple sclerosis in the 'suboptimal therapy' patient population.

Background: Highly active (HA) relapsing remitting multiple sclerosis (RRMS) is associated with frequent relapses and high burden of disease/disability. Natalizumab is licensed for HA RRMS, including rapidly evolving severe (RES) (≥2 relapses in previous year) and sub-optimally treated (SOT) (≥1 relapse in previous year despite treatment) populations. However, there is limited RCT evidence in the SOT subpopulation.

Exploring how the design and provision of digital self-management technology can improve the uptake by older adults with chronic kidney disease, diabetes and dementia: A modified e-Delphi study.

As development and introduction of digital self-management technologies continues to increase, the gap between those who can benefit, and those who cannot correspondingly widens. This research aimed to explore the use of digital self-management technology by older adults with three highly-prevalent long-term conditions (chronic kidney disease, diabetes and dementia), and build expert consensus across the conditions on changes needed to improve effective usage. This qualitative research involved a modified e-Delphi Study.

Protocol for a feasibility randomised controlled trial of the 'Outdoor' mobility intervention for older adults after hip fracture.

Background: A high proportion of patients do not regain outdoor mobility after hip fracture. Rehabilitation explicitly targeting outdoor mobility is needed to enable these older adults to recover activities which they value most. The overarching aim of this study is to determine the feasibility of a randomised controlled trial which aims to assess the clinical- and cost-effectiveness of an intervention designed to enable recovery of outdoor mobility among older adults after hip fracture (the OUTDOOR intervention).

High incidence of femoroacetabular impingement deformity in bi-column acetabular fractures.

Introduction: Dynamic interaction of cam and pincer deformities can result in pathological contact forces in femoroacetabular impingement (FAI) syndrome. Similar deformities were noted during acetabular fracture reconstruction. We hypothesise that the prevalence of FAI deformity is higher in patients sustaining acetabular fractures than in a control group.

Key components of rehabilitation programmes for adults with complex fractures following traumatic injury: A scoping review.

Introduction: Complex fractures are severe injuries that cause considerable disability, particularly in the working population. Effective rehabilitation is essential to achieve good outcomes, however, it is unclear what the best rehabilitation strategy is for adults with complex fractures, after their discharge from hospital. The aim of this scoping review was to identify and map the breadth of evidence available on this topic.

Development and validation of metrics for assessment of ultrasound-guided fascial block skills.

Background: As few anaesthetists provide lumbar erector spinae block for disc surgery, there is a need to provide training to enable a randomised controlled trial investigating analgesia after painful spinal surgery (NIHR153170). The primary objective of the study was to develop and measure the construct validity of a checklist for assessment of skills in performing lumbar and thoracic erector spinae fascial plane injection using soft-embalmed Thiel cadavers.

Methods: Twenty-four UK consultant regional anaesthetists completed two iterations of a Delphi questionnaire.

The Association Between Trajectories of Self-reported Psychotic Experiences and Continuity of Mental Health Care in a Longitudinal Cohort of Adolescents and Young Adults.

Background And Hypothesis: Young people (YP) with psychotic experiences (PE) have an increased risk of developing a psychiatric disorder. Therefore, knowledge on continuity of care from child and adolescent (CAMHS) to adult mental health services (AMHS) in relation to PE is important. Here, we investigated whether the self-reported trajectories of persistent PE were associated with likelihood of transition to AMHS and mental health outcomes.

Contrastive machine learning reveals Parkinson's disease specific features associated with disease severity and progression.

Parkinson's disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach to analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients and 366 controls, aiming to disentangle PD-specific neuroanatomical alterations. The results reveal that these neuroanatomical alterations in PD are correlated with individual differences in dopamine transporter binding deficit, neurodegeneration biomarkers, and clinical severity and progression.

Patient experiences and desires for recovery after ankle fracture surgery.

Objective: This study investigates patients' experiences of commencing weight-bearing after ankle fracture surgery and their recovery priorities to inform a new rehabilitation intervention.

Methods: Embedded within the Weight bearing in Ankle Fractures (WAX) trial, this qualitative study conducted semi-structured interviews with patients following ankle fracture surgery. The Behaviour Change Wheel (BCW) framework guided the interview questions to ensure comprehensive domain coverage.

Development and evaluation of a societal core robotic surgery accreditation curriculum for the UK.

Standardised proficiency-based progression is the cornerstone of safe robotic skills acquisition, however, is currently lacking within surgical training curricula. Expert consensuses have defined a modular pathway to accredit surgeons. This study aimed to address the lack of a formal, pre-clinical core robotic skills, proficiency-based accreditation curriculum in the UK.

Blood Biomarkers of Long COVID: A Systematic Review.

Background: Long coronavirus disease (COVID; LC) affects millions of people worldwide. The exact mechanisms which result in a broad, undulating and detrimental symptom profile remain unknown. Blood biomarkers associated with LC have been described; however, consensus on these remains elusive, in part due to a lack of continuity between studies on a universally accepted definition of LC.

Flash Glucose Monitoring is Associated with HbA1c Improvement in Type 2 Diabetes Managed with Multiple Daily Injections of Insulin in the UK: A Retrospective Observational Study.

Introduction: There is a growing body of evidence demonstrating the benefit of flash glucose monitoring in people living with type 2 diabetes mellitus (T2DM). This real-world study aimed to evaluate the effect of initiating flash glucose monitoring on change in HbA1c after 3-6 months in adults living with T2DM treated with multiple daily injections of insulin.

Methods: A retrospective observational study using data from ten clinical centres in the UK for adults with T2DM treated with multiple daily injections of insulin for at least 1 year was conducted.

The management of tarsal tunnel syndrome: A scoping review.

Background: Tarsal tunnel syndrome, also known as posterior tibial neuralgia, is a compressive neuropathy of the posterior tibial nerve or one of its divisions (calcaneal, lateral plantar or medial plantar nerve) within the tarsal tunnel. This scoping review aims to systematically map and summarise current literature regarding the management of tarsal tunnel syndrome.

Methods: PubMed, Embase, Emcare, Medline and Cinahl were searched using the terms 'tarsal tunnel', 'syndrome', 'entrapment', 'compression', 'posterior tibial', 'neuropathy' and 'neuralgia.