Immunotherapy-Resistant Neuropathic Pain and Fatigue Predict Quality-of-Life in Contactin-Associated Protein-Like 2 Antibody Disease.

The long-term clinical outcomes and associated prognostic factors in contactin-associated protein-like 2 (CASPR2)-antibody diseases are unknown. A total of 75 participants with CASPR2 antibodies were longitudinally assessed for disability, quality-of-life, and chronic pain. Although most symptoms improved within 6 months of treatment, neuropathic pain and fatigue were the most immunotherapy refractory, and persisted for up to 6 years.

Impact of Centralisation of Radical Prostatectomy Driven by the Introduction of Robotic Systems on Positive Surgical Margin and Biochemical Recurrence in pT2 Prostate Cancer.

Background: To assess how centralisation of cancer services via robotic surgery influenced positive surgical margin (PSM) occurrence and its associated risk of biochemical recurrence (BCR) in cases of pT2 prostate cancer (PC).

Methods: Retrospective analysis of all radical prostatectomy (RP) cases performed in the West of Scotland during the period from January 2013 to June 2022. Primary outcomes were PSM and BCR.

A contentious intervention to support the medical workforce: a case study of the policy of introducing physician associates in the United Kingdom.

Background: Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload.

Case Presentation: In the early 2000s the United Kingdom created a new occupational role, that of physician assistant.

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Dynamical constraints on neural population activity.

The manner in which neural activity unfolds over time is thought to be central to sensory, motor and cognitive functions in the brain. Network models have long posited that the brain's computations involve time courses of activity that are shaped by the underlying network. A prediction from this view is that the activity time courses should be difficult to violate.

Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease.

Animal models that accurately reflect COVID-19 are vital for understanding mechanisms of disease and advancing development of improved vaccines and therapeutics. Pigs are increasingly recognized as valuable models for human disease due to their genetic, anatomical, physiological, and immunological similarities to humans, and they present a more ethically viable alternative to non-human primates. However, pigs are not susceptible to SARS-CoV-2 infection which limits their utility as a model.

Switching to faricimab from the current anti-VEGF therapy: evidence-based expert recommendations.

Dual inhibition of the angiopoietin (Ang)/Tie and vascular endothelial growth factor (VEGF) signalling pathways in patients with retinal diseases, such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME), may induce greater vascular stability and contribute to increased treatment efficacy and durability compared with treatments that only target the VEGF pathway. Faricimab, a bispecific intravitreal agent that inhibits both VEGF and Ang-2, is the first injectable ophthalmic drug to achieve treatment intervals of up to 16 weeks in Phase 3 studies for nAMD and DME while exhibiting improvements in visual acuity and retinal thickness. Data from real-world studies have supported the safety, visual and anatomic benefits and durability of faricimab, even in patients who were previously treated with other intravitreal agents.

Scoping review: The effects of diet, physical activity and sleep on motor and physical fatigue in people with multiple sclerosis.

Physical and motor fatigue are debilitating symptoms common in multiple sclerosis (MS). Lifestyle interventions may be effective in managing MS-related fatigue. This scoping review aims to: (i) identify and summarise lifestyle interventions including those focused on diet, physical activity, and sleep, or multicomponent interventions for physical and motor fatigue management in MS; and (ii) provide recommendations for future research in this area.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial.

Background: Aspirin is a simple, globally available medication that has been shown to reduce the incidence of colorectal cancer. We aimed to evaluate the safety and efficacy of aspirin in the secondary prevention of colorectal cancer.

Methods: This phase 3, randomised, double-blind, placebo-controlled trial was conducted at 66 centres across 11 countries and territories (ten in Asia-Pacific; one in the Middle East).

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer.

Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.

Self-directed violence and unclear intent presentation within a major trauma system. A multisite analysis.

Background: Determining trauma as an act of Self-directed violence (SDV) or from high risk or unclear behaviours is challenging for trauma clinicians and may be affected by patient sex and mechanism of injury. The aim of this study was to examine the differences in characteristics and outcomes between those who have intentionally directed violence towards themselves with those of unclear intent, within a regional trauma system.

Methods: Data was collected between January 2018 and December 2021 in patients who had been identified as a result of either self-directed violence (SDV) defined as any intentional act that can cause injury to one's self, including death or participated in high-risk behaviours, where the intent was unclear (UI).

4D flow cardiac magnetic resonance in pediatric congenital heart disease: Insights from over four years of clinical practice.

Background: Congenital heart diseases (CHDs) are common birth defects. This work presents over four years of clinical experience of 4D flow cardiovascular magnetic resonance (CMR), highlighting its value for pediatric CHD.

Methods: Children with various CHD diagnoses (n = 298) were examined on a 1.

The management of people with epilepsy in a city wide care home service, the impact of a GP with Special Interest in epilepsy, and Enhanced Health in Care Homes Framework.

Background: The incidence of epilepsy increases with age, especially in people diagnosed with dementia. Seizures in an elderly population are likely to have a focal onset, for which sodium channel blockers are the drug of choice. This study reviews the clinical needs and care of people with epilepsy (PWE) in a city wide care home service and assessing the impact of a GP with Special Interest in epilepsy (GPwSIe).

Translation, adaptation and validation of an epilepsy screening instrument in two Ghanaian languages.

Introduction: The prevalence of epilepsy in sub-Saharan Africa varies considerably, and the exact estimate for Ghana remains unclear, particularly in peri-urban areas where data are scarce. More community-based studies are required to understand better the actual burden of epilepsy in these areas and the difficulties in accessing healthcare.

Objective: To adapt and validate a household survey epilepsy-screening instrument in Shai-Osudoku and Ningo-Prampram District of Greater Accra Region, Ghana.

Assessing the capture of sociodemographic information in electronic medical records to inform clinical decision making.

There is a growing need to document sociodemographic factors in electronic medical records to produce representative cohorts for medical research and to perform focused research for potentially vulnerable populations. The objective of this work was to assess the content of family physicians' electronic medical records and characterize the quality of the documentation of sociodemographic characteristics. Descriptive statistics were reported for each sociodemographic characteristic.

Permeability Benchmarking: Guidelines for Comparing , , and Measurements.

Permeability is a measure of the degree to which cells can transport molecules across biological barriers. Units of permeability are distance per unit time (typically cm/s), where accurate measurements are needed to define drug delivery in homeostasis and to model dysfunction occurring during disease. This perspective offers a set of community-led guidelines to benchmark permeability data across multidisciplinary approaches and different biological contexts.

Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.

Reservoir-Type Subcutaneous Implantable Devices Containing Porous Rate Controlling Membranes for Sustained Delivery of Risperidone.

Implantable drug delivery systems are crucial for achieving sustained delivery of active compounds to specific sites or systemic circulation. In this study, a novel reservoir-type implant combining a biodegradable rate-controlling membrane with a drug-containing core prepared using direct compression techniques is developed. The membrane is composed of poly(caprolactone) (PCL), and risperidone (RIS) served as the model drug.