Correcting a pathogenic mitochondrial DNA mutation by base editing in mice.

Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.

Refractory Psychosis as a Red Flag for End of Life in Individuals With Dementia With Lewy Bodies: A Case Series and Re-analysis of Prior Qualitative Data.

Objectives: Many individuals with dementia with Lewy bodies (DLB) die of disease-related complications, but predicting the end of life can be challenging. We identified a phenotype associated with approaching end of life.

Methods: We present 4 exemplar cases where individuals with DLB experienced refractory psychosis before death.

Structural and functional brain correlates of the neutrophil- and monocyte-to-lymphocyte ratio in neuropsychiatric disorders.

Skews in the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) increasingly demonstrate prognostic capability in a range of acute and chronic mental health conditions. There has been a recent uptick in structural and functional magnetic responance imaging data corroborating the role of NLR and MLR in a cluster of neuropsychiatric disorders that are characterized by cognitive, affective, and psychomotor dysfunction. Moreover, these deficits are mostly evident in setting of acute and chronic disease comorbidity implicating aging and immunosenescent processes in the manifestation of these geriatric syndromes.

Association of safer smoking supply distribution with participant encounters and naloxone distribution from syringe services programs: Findings from the National Survey of Syringe Services Programs in the United States.

Background: In response to the recent and growing shift from injecting heroin to smoking fentanyl, an increasing number of syringe services programs (SSPs) in the United States are distributing safer smoking supplies. There is a lack of research on whether safer smoking supply distribution is associated with increased SSP engagement and naloxone distribution from SSPs. Therefore, we aimed to assess predictors of safer smoking supply distribution by SSPs and estimate associations between safer smoking supply distribution and scale of harm reduction services.

Safety and feasibility of En-bloc holmium laser enucleation for very large prostates (> 200 cc) with trainee involvement.

Objectives: To evaluate the safety and feasibility of "en-bloc" Holmium Laser Enucleation of the Prostate (HoLEP) with trainee involvement in patients with prostates larger than 200 cc.

Patients And Methods: A retrospective analysis was conducted on patients undergoing HoLEP using the "en-bloc" technique for prostate sizes > 200 cc between July-2017 and December-2023 at an academic teaching hospital. Perioperative data was collected, including patient demographics, clinical parameters, operative details and functional outcomes.

Randomized Controlled Trial of the Effects of High-Dose Ondansetron on Clinical Symptoms and Brain Connectivity in Obsessive-Compulsive and Tic Disorders.

Objective: Sensory phenomena (SP) are aversive sensations driving repetitive behaviors in obsessive-compulsive disorder (OCD) and Tourette's disorder that are not well addressed by standard treatments. SP are related to the functioning of an interoceptive-sensorimotor circuit that may be modulated by the 5-HT receptor antagonist ondansetron. The present study employed an experimental medicine approach to test the effects of 4 weeks of high-dose ondansetron compared to placebo on SP severity and brain connectivity in a cohort of individuals with OCD and/or Tourette's disorder.

The relationship between optical coherence tomography and magnetic resonance imaging measurements in people with multiple sclerosis: A systematic review and meta-analysis.

Background: Several studies show that optical coherence tomography (OCT) metrics e with cognition, disability, and brain structure in people with multiple sclerosis (PwMS). This review the correlation between OCT parameters and magnetic resonance imaging (MRI) measurements in PwMS.

Methods: A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was performed, including studies published in English up to November 29, 2024 to identify studies reporting quantitative data on the correlation between baseline OCT parameters and MRI measurements in PwMS.

Designer Organs: Ethical Genetic Modifications in the Era of Machine Perfusion.

Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant.

Feasibility of a Mobile App-Based Cognitive-Behavioral Perinatal Skills Program: Protocol for Nonrandomized Pilot Trial.

Background: Mental illness is one of the top causes of preventable pregnancy-related deaths in the United States. There are many barriers that interfere with the ability of perinatal individuals to access traditional mental health care. Digital health interventions, including app-based programs, have the potential to increase access to useful tools for these individuals.

Comprehensive Echocardiographic Protocol for Pigs with Emphasis on Diastolic Function: Advantages over MRI Assessment.

Swine are increasingly utilized in cardiovascular research due to their anatomical and physiological similarities to humans, particularly for studying diastolic dysfunction. While MRI offers excellent structural imaging, echocardiography provides superior real-time assessment of diastolic parameters. To address the lack of standardized methods and reduce variability across studies, we present a comprehensive guide for performing echocardiography in Yorkshire pigs, detailing anatomical considerations, equipment requirements, and technical approaches.

Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction.

In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood.

Advancements in Wound Bed Preparation of Chronic Wounds.

Chronic wounds are notoriously challenging to heal as they are often halted in their normal healing process. The concept of TIME (Tissue, Inflammation/Infection, Moisture imbalance, Epithelial edge advancement) has been widely utilized in clinical practice to prepare wound beds and promote healing, particularly in longstanding wounds. Traditional methods of wound bed preparation are often inadequate in healing chronic wounds or they may not be tolerated by patients.

Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas.

Purpose: Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti-PD-1 antibody, in advanced sarcomas.

Methods: BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years.

Integrated care for mental health in epilepsy: A systematic review and meta-synthesis by the International League Against Epilepsy Integrated Mental Health Care Pathways Task Force.

Mental health (MH) comorbidities are prevalent among people with epilepsy (PWE), but many experience challenges accessing care. To address this, suggestions have been made to integrate MH care into epilepsy care settings, yet the current approaches, benefits, and implementation determinants to MH care integration are unclear. This review aims to synthesize existing integrated MH care models for PWE to inform the development and planning of future initiatives.

Cancer History, Antiphospholipid Syndrome, and Lupus Anticoagulant: A Perfect Storm for Thrombosis.

Cancer and antiphospholipid syndrome (APS) independently increase thrombotic risk, and their coexistence can create a particularly hazardous prothrombotic state. This case report aims to highlight the complex challenges in managing concurrent thrombotic and hemorrhagic events in patients with a history of cancer and APS. The combination of these conditions presents a rare and difficult clinical scenario, requiring careful consideration in anticoagulation management.

Characterizing Wellness Initiatives in Academic Radiation Oncology Departments.

Purpose: Burnout is prevalent in radiation oncology (RO), and an increased focus on promoting physician wellness and formalizing wellness-directed efforts has transpired in recent years. We aimed to characterize current wellness leadership positions and efforts within academic RO departments.

Methods And Materials: Academic RO department chairs were contacted to inquire whether they had a departmental wellness leader with a request for leader contact information, if applicable.

Sleep alterations following elective shoulder surgery: A systematic review.

Background: Poor sleep quality due to nocturnal pain is increasingly reported as a major symptom in several shoulder pathologies. Sleep disturbance has been reported in up to 89% after rotator cuff tears and is frequently reported as the primary reason for referring patients to surgery. As a result, it is important to understand the impact of shoulder surgery on a patient's sleep quality.

Myocardial Inflammation in Cardiac Transthyretin Amyloidosis: Prevalence and Potential Prognostic Implications.

Background: Despite previous histopathologic evidence for its presence, the role of myocardial inflammation in the development and progression of cardiac transthyretin amyloidosis (ATTR-CA) remains insufficiently understood. Thus, this study sought to characterize the prevalence and potential prognostic implications of myocardial inflammation in ATTR-CA.

Methods: A retrospective observational study including patients with ATTR-CA diagnosed by endomyocardial biopsy was conducted.

Cognivue characterizes amyloid status and preclinical Alzheimer's disease in biomarker confirmed cohorts in the Bio-Hermes Study.

Background: Cognivue is an FDA-cleared computerized cognitive test to screen for cognitive impairment included in the Bio-Hermes Study to test blood-based and digital biomarkers' ability to screen for mild cognitive impairment (MCI) and Alzheimer's disease (AD). A subset of cognitively normal individuals have amyloid deposition (Preclinical AD) but no current assessment can identify these individuals in the absence of expensive biomarkers.

Objective: We examined differences in Cognivue performance between amyloid positive and amyloid negative individuals and whether Cognivue could differentiate True Controls (cognitively normal/amyloid negative), Preclinical AD (cognitively normal/amyloid positive), and MCI due to AD (MCI-AD, cognitively impaired/amyloid positive).