Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine.

Background: The evidence informing the harms of gabapentin use are at risk of bias from comparing users with nonusers.

Objective: To describe the risk for fall-related outcomes in older adults starting treatment with gabapentin versus duloxetine.

Design: New user, active comparator study using a target trial emulation framework.

Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder.

Blood-based biomarkers for Alzheimer's disease (AD) pathology have been intensively investigated as markers for AD-related neurodegeneration. Comorbid AD pathology is common in dementia with Lewy bodies (DLB). Accordingly, we hypothesized that plasma biomarkers associated with AD pathology might be useful to predict DLB in a cohort of idiopathic/isolated REM sleep behavior disorder (iRBD), an incipient synucleinopathy.

Longitudinal changes of macular neurodegenerative and vascular abnormalities on OCTA in sickle cell disease.

Purpose: To evaluate the presence and progression of maculopathy in patients with sickle cell disease (SCD) using Optical Coherence Tomography (OCT) and OCT-Angiography (OCTA), and to identify clinical/laboratory risk factors for progression during follow-up.

Methods: Complete ophthalmic examination, including fundoscopy and macular SD-OCT/OCTA scans, was performed in consecutive SCD-patients (HbSS/HbSβ0/HbSβ+/HbSC genotype) during baseline and follow-up visits. SCR stage was based on fundoscopy instead of the Goldberg classification, since fluorescein angiography was not routinely used.

Intraocular Inflammation (IOI) Associated with Faricimab Therapy: One-year Real World Outcomes.

Purpose: To report one-year real-world evidence on intraocular inflammation (IOI) adverse events (AEs) in patients undergoing faricimab therapy in a tertiary care hospital.

Methods: A retrospective review of electronic medical records was conducted for patients receiving faricimab treatment for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) at Moorfields Eye Hospital between September 1st, 2022, and August 31st, 2023. The primary outcome was the incidence of IOI (excluding endophthalmitis).

A Core Outcome Set for Adult General ICU Patients.

Objectives: Randomized clinical trials informing clinical practice (e.g., like large, pragmatic, and late-phase trials) should ideally mostly use harmonized outcomes that are important to patients, family members, clinicians, and researchers.

Completion of lunar magma ocean solidification at 4.43 Ga.

Crystallization of the lunar magma ocean yielded a chemically unique liquid residuum named KREEP. This component is expressed as a large patch on the near side of the Moon and a possible smaller patch in the northwest portion of the Moon's South Pole-Aitken basin on the far side. Thermal models estimate that the crystallization of the lunar magma ocean (LMO) could have spanned from 10 and 200 My, while studies of radioactive decay systems have yielded inconsistent ages for the completion of LMO crystallization covering over 160 My.

Pan-European atmospheric lead pollution, enhanced blood lead levels, and cognitive decline from Roman-era mining and smelting.

Ancient texts and archaeological evidence indicate substantial lead exposure during antiquity that potentially impacted human health. Although lead exposure routes were many and included the use of glazed tablewares, paints, cosmetics, and even intentional ingestion, the most significant for the nonelite, rural majority of the population may have been through background air pollution from mining and smelting of silver and lead ores that underpinned the Roman economy. Here, we determined potential health effects of this air pollution using Arctic ice core measurements of Roman-era lead pollution, atmospheric modeling, and modern epidemiology-based relationships between air concentrations, blood lead levels (BLLs), and cognitive decline.

Proton Accumulation Modulated Surface Potential in Proton Conducting Ceramics Revealed by Near-Ambient Pressure X-ray Photoelectron Spectroscopy.

Proton conducting electrochemical cells (PCECs) are efficient and clean intermediate-temperature energy conversion devices. The proton concentration across the PCECs is often nonuniform, and characterizing the distribution of proton concentration can help to locate the position of rate-limiting reactions. However, the determination of the local proton concentration under operating conditions remains challenging.

Modelling the health labour market outlook in Kenya: Supply, needs and investment requirements for health workers, 2021-2035.

Kenya is committed to achieving Universal Health Coverage (UHC) within its devolved health system in which significant investments have been made in health infrastructure, workforce development, and service delivery. Despite these efforts, the country faces considerable health workforce challenges. To address these, the Ministry of Health undertook a comprehensive Health Labour Market Analysis (HLMA) in 2022 to generate evidence supporting the development of responsive health workforce policies.

Role and modulation of various spinal pathways for human upper limb control in different gravity conditions.

Humans can perform movements in various physical environments and positions (corresponding to different experienced gravity), requiring the interaction of the musculoskeletal system, the neural system and the external environment. The neural system is itself comprised of several interactive components, from the brain mainly conducting motor planning, to the spinal cord (SC) implementing its own motor control centres through sensory reflexes. Nevertheless, it remains unclear whether similar movements in various environmental dynamics necessitate adapting modulation at the brain level, correcting modulation at the spinal level, or both.

Tetrafluoro(aryl)sulfanylated Bicyclopentane Crystals That Self-Destruct upon Cooling.

Whereas single crystals of organic compounds that respond to heat or light have been reported and studied in detail, studies on crystalline organic compounds that elicit an extreme mechanical response are relatively rare in the chemical literature. A tetrafluoro(aryl)sulfanylated bicyclopentane synthesized in our laboratory was discovered to exhibit such behavior; i.e.

Fragment-to-Lead Medicinal Chemistry Publications in 2023.

This Perspective summarizes successful fragment-to-lead (F2L) studies that were published in 2023 and is the ninth installment in an annual series. A tabulated summary of the relevant articles published in 2023 is provided (17 entries from 16 articles), and a comparison of the target classes, screening methods, and overall fragment or lead property trends for 2023 examples and for the combined entries over the years 2015-2023 is discussed. In addition, we identify several trends and innovations in the 2023 literature that promise to further increase the success of fragment-based drug discovery (FBDD), particularly in the areas of NMR and virtual screening, fragment library design, and fragment linking.

Higher vulnerability to poor circadian light hygiene in individuals with a history of COVID-19.

Seven-day actigraphy was performed within 1 month in 122 community-dwelling adults (mean age 24.40 y, 31 (25.4%) men) in the same city of Tyumen, Russia.

Thermal Adaptation in Worldwide Collections of a Major Fungal Pathogen.

Adaptation to new climates poses a significant challenge for plant pathogens during range expansion, highlighting the importance of understanding their response to climate to accurately forecast future disease outbreaks. The wheat pathogen is ubiquitous across most wheat production regions distributed across diverse climate zones. We explored the genetic architecture of thermal adaptation using a global collection of 411 strains that were phenotyped across a wide range of temperatures and then included in a genome-wide association study.

Soft Robotics in Upper Limb Neurorehabilitation and Assistance: Current Clinical Evidence and Recommendations.

Soft robotics is gaining interest in rehabilitation applications, bringing new opportunities to offset the loss of upper limb motor function following neurological, neuromuscular, or traumatic injuries. Unlike conventional rigid robotics, the added softness in linkages or joints promises to make rehabilitation robots compliant, which translates into higher levels of safety, comfort, usability, and portability, opening the door for these rehabilitation technologies to be used in daily life. While several reviews documented the different technical implementations of soft rehabilitation robots, it is essential to discuss the growing clinical evidence on the feasibility and effectiveness of using this technology for rehabilitative and assistive purposes, whether softness brings the expected advantages from the perspective of end users, and how we should proceed in the future of this field.

The Oxidoreductase Retinol Saturase in Thyroid Gland Is Regulated by Hypothyroidism and Iodide Overload and Its Deletion Impairs Metabolic Homeostasis in Mice.

Thyroid hormones (TH) are major regulators of cell differentiation, growth, and metabolic rate. TH synthesis in the thyroid gland requires high amounts of HO to oxidize iodide for the iodination of thyroglobulin (TG). Retinol Saturase (RetSat) is an oxidoreductase implicated in dihydroretinol formation and cellular sensitivity toward peroxides and ferroptosis.

Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation.

Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB, or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC.

The Effects of alfapump on Ascites Control and Quality of Life in Patients with Cirrhosis and Recurrent or Refractory Ascites.

Aim: To assess the safety and efficacy of alfapump on ascites control and quality of life in these patients.

Methods: Patients with cirrhosis and RA requiring ≥2 TPs 30 days prior were enrolled and followed for 24 months (M) post-implant. Primary efficacy endpoint assessed at 6M was reduction in paracentesis requirement; safety end point was device related adverse events resulting in intervention, explant, or death.

NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.

Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation occurring via T-cell receptor engagement. In this study, we report the development and preclinical characterization of NI-3201, a PD-L1×CD28 bispecific antibody generated on the κλ-body platform that was designed to promote T-cell activity and antitumor function through a dual mechanism of action.

Rapidly spreading with OXA-48-like carbapenemases.

(mostly , ) with OXA-48-like carbapenemases (e.g., OXA-48, -181, -232, -244) are undermining the global efficiency of carbapenem therapy.

Sleep-Related Breathing Disorders and Lower Urinary Tract Dysfunction in Children and Adolescents: A Scoping Review.

Aims: Sleep disordered breathing (SDB), lower urinary tract dysfunction (LUTD), and enuresis (NE) are common in children and adolescents and have serious consequences, especially on social and emotional development. Even though much is known about the association between SDB and NE among adults, the number of articles in children and adolescents is limited. Therefore, the aim of the present scoping review was to map out the current knowledge about SDB and LUTD in children and adolescents.

Artificial Metalloenzymes with Two Catalytic Cofactors for Tandem Abiotic Transformations.

Artificial metalloenzymes (ArMs) enable the integration of abiotic cofactors within a native protein scaffold, allowing for non-natural catalytic activities. Previous ArMs, however, have primarily relied on single cofactor systems, limiting them to only one catalytic function. Here we present an approach to construct ArMs embedding two catalytic cofactors based on the biotin-streptavidin technology.

Trends in Demographic, Clinical, Socioeconomic, and Facility-Specific Factors Linked to Eyelid Melanoma Survival: A National Cancer Database Analysis.

Purpose: This study aimed to analyze demographic, clinical, socioeconomic, and facility-specific factors affecting the survival outcomes of patients diagnosed with eyelid melanoma (EM) between 2004 and 2017 using data from the National Cancer Database.

Methods: Cases of EM diagnosed between 2004 and 2017 were identified using the National Cancer Database. Patient demographic data, tumor stage (American Joint Committee on Cancer TNM classification), treatment modalities, and socioeconomic variables were collected.