Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.

α-Synucleinopathies constitute a spectrum of neurodegenerative disorders, including Parkinson's disease (PD), Lewy body dementia (LBD), Multiple System Atrophy (MSA), and Alzheimer's disease concurrent with LBD (AD-LBD). These disorders are unified by a pathological hallmark: aberrant misfolding and accumulation of α-synuclein (α-syn). This review delves into the pivotal role of α-syn, the key agent in α-synucleinopathy pathophysiology, and provides a survey of potential therapeutics that target cell-to-cell spread of pathologic α-syn.

Lung injury in myocardial infarction-associated cardiogenic shock supported by venoarterial extracorporeal membrane oxygenation: a scoping review.

Background: Acute lung injury and acute respiratory failure are frequent complications of cardiogenic shock and are associated with increased morbidity and mortality. Even with increased use of temporary mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation (VA-ECMO), acute lung injury related to cardiogenic shock continues to have a determinantal effect on patient outcomes.

Objectives: To summarize potential mechanisms of acute lung injury described in patients with cardiogenic shock supported by VA-ECMO and determine current knowledge gaps.

Investigating the association between human brainstem microstructural integrity and hypertension using magnetic resonance relaxometry.

The brainstem plays a vital role in regulating blood pressure, and disruptions to its neural pathways have been linked to hypertension. However, it remains unclear whether subtle microstructural changes in the brainstem are associated with an individual's blood pressure status. This exploratory, cross-sectional study investigated the relationship between brainstem microstructure, myelination, and hypertensive status in 116 cognitively unimpaired adults (aged 22-94 years).

Metformin intake and risk of metabolic acidosis after radical cystectomy with urinary diversion: A comparative study using data from the TriNetX research network.

Purpose: To investigate the association of diabetes mellitus and metformin use with metabolic acidosis risk after radical cystectomy (RC) and urinary diversion for bladder cancer.

Materials And Methods: This retrospective cohort study used TriNetX Research Network data. Patients undergoing RC with continent diversion or ileal conduit for bladder cancer were identified using International Classification of Diseases, 10th Revision (ICD-10) and ICD-10 Procedure Coding System (ICD-10-PCS) codes.

Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins.

Computational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT.

Worldwide epidemiology of paediatric multiple sclerosis: data from the Multiple Sclerosis International Federation Atlas of MS, third edition.

Background: Limited data are available on the global rates of paediatric multiple sclerosis. Here, we report on the estimated worldwide prevalence of paediatric MS.

Methods: We included paediatric prevalence data in 2020-2022 (Multiple Sclerosis International Federation Atlas of MS) and the prevalence of child neurologists (International Child Neurology Association).

Discovery of Orally Available Prodrugs of Itaconate and Derivatives.

Itaconate, an endogenous immunomodulator from the tricarboxylic acid (TCA) cycle, shows therapeutic effects in various disease models, but is highly polar with poor cellular permeability. We previously reported a novel, topical itaconate derivative, SCD-153, for the treatment of alopecia areata. Here, we present the discovery of orally available itaconate derivatives for systemic and skin disorders.

Nail Unit Melanoma Treated with Mohs Micrographic Surgery: Technique, Local Recurrence Rate, and Surgical Outcomes.

Background: Nail unit melanoma (NUM) is increasingly treated with digit-sparing surgery, but few published case series describe Mohs micrographic surgery (MMS) for NUM.

Objective: To describe the surgical technique, local recurrence rates, and reconstruction method for a large series of NUM treated with MMS using MART-1 immunostaining.

Methods: Biopsy-proven NUM treated with MMS-MART-1 were identified from a prospectively maintained database (2008-2023).

How Do Clinicians Use Quotations in Goals of Care Notes?

Background: Quoting patients in electronic medical record (EMR) notes is controversial. Quotations may be used to promote accuracy in documentation. However they also may be used to cast skepticism on patient speech.

Long-term Mental Health Morbidity in Adult Survivors of COVID-19 Critical Illness - A Population-based Cohort Study.

Background: Survivorship after coronavirus disease 2019 (COVID-19) critical illness may be associated with important long-term sequelae, but little is known regarding mental health outcomes.

Research Question: What is the association between COVID-19 critical illness and new post-discharge mental health diagnoses.

Study Design: AND METHODS: We conducted a population-based cohort study in Ontario, Canada (January 1, 2020-March 31, 2022).

Risk of bias assessment tools often addressed items not related to risk of bias and used numerical scores.

Objective: We aimed to determine whether the existing risk of bias assessment tools addressed constructs other than risk of bias or internal validity, and whether they used numerical scores to express quality, which is discouraged and may be a misleading approach.

Methods: We searched Ovid MEDLINE and Embase to identify quality appraisal tools across all disciplines in human health research. Tools designed specifically to evaluate reporting quality were excluded.

Use of Harms trabeculotome to assist failed microcatheter advancement during trabeculotomy in primary congenital glaucoma.

We report the use of the Harms trabeculotome to facilitate 360° microcatheter advancement during illuminated microcatheter-assisted circumferential trabeculotomy (IMCT) ab externo in a 3-month-old infant with bilateral primary congenital glaucoma who required repeat surgery. The illuminated microcatheter was advanced 270°, from 9 to 6 o'clock; however, a focal blockage occurred, and, despite viscodilation, further advancement was not possible. The surgeon introduced a right Harms trabeculotome in the opposite direction, counterclockwise through the same scleral flap.

Embracing the Future of Clinical Trials in Radiotherapy: An NRG Oncology CIRO Technology Retreat Whitepaper on Pioneering Technologies and AI-Driven Solutions.

This white paper examines the potential of pioneering technologies and artificial intelligence (AI)-driven solutions in advancing clinical trials involving radiotherapy. As the field of radiotherapy evolves, the integration of cutting-edge approaches such as radiopharmaceutical dosimetry, FLASH radiotherapy, image-guided radiation therapy (IGRT), and AI promises to improve treatment planning, patient care, and outcomes. Additionally, recent advancements in quantum science, linear energy transfer/relative biological effect (LET/RBE), and the combination of radiotherapy and immunotherapy create new avenues for innovation in clinical trials.

Academic Achievement of Children With Neurofibromatosis Type 1.

Background And Objectives: Learning difficulties are frequently reported in children with neurofibromatosis type 1 (NF1), yet little is known about the extent and predictors of their academic functions across ages. We aimed to examine the developmental patterns of academic achievement in these children from childhood to adolescence and how these patterns differ across demographic and NF1-related disease factors.

Methods: This cross-sectional study integrated data of 1512 children with NF1 (mean age, 11.

Functional movement disorders in dopa-responsive dystonia.

Background: Functional neurological movement disorders are common and disabling. Little is known about their coexistence with other non-functional movement disorders and their impact on the general disease burden.

Objectives: Investigating frequency and characteristics of functional movement disorders in GCH1-positive dopa-responsive dystonia patients.

Does exercise demonstrate a dose-dependent benefit with cognition in Parkinson's disease?

Background: Exercise confers motor benefits in Parkinson's disease (PD) and may even have disease modifying effects. While the impact of exercise on motor symptoms and quality of life is well-studied in PD, its relationship with cognitive performance warrants further attention.

Methods: In people with PD, self-reported exercise information was quantified using the Rapid Assessment of Physical Activity (RAPA).

Impact of Subsequent Fellowship on Urology Chief Resident Case Log Volumes.

Objective: To characterize the impact of subsequent fellowship on the case log experience of trainees throughout their residency and specifically their chief resident year.

Materials And Methods: Urology resident case logs from 2010 to 2022 were obtained from 13 institutions for total residency and chief years. Five categorized index procedures were included for analysis: General Urology; Endourology; Reconstructive Urology; Urologic Oncology; and Pediatric Urology.

Harmonizing excellence: Crafting the nexus of competencies, standards, and degree demands in nurse practitioner education.

Nurse practitioner (NP) programs have a long history of producing safe and competent NPs; however, bold, transformative leadership is needed to set a minimum standard for quality NP education to support a 21st-century healthcare system. This paper is a call to action for leaders in NP education to transition NP education to the DNP degree utilizing the 2022 National Task Force Standards for Quality NP Education and a competency-based approach as defined in the 2021 AACN Essentials. There is now an opportunity to redesign healthcare systems with quality and equity as a primary consideration and DNP-prepared NPs are positioned to lead this redesign.

Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non-MSI-H/non-dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results.

Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non-MSI-H/non-dMMR advanced EC (cohort D).

Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.

Lower Extremity Penetrating Trauma Care Associated With Race and Income in the United States of America.

Introduction: For lower extremity penetrating traumas (LEPT), the impact of race and insurance status, as a surrogate of socioeconomic status, is still not fully elucidated. This study aims to explore the relationship between these variables and the likelihood of receiving an amputation for LEPT to further identify disparities in trauma care.

Methods: We analyzed the 2017-2019 Trauma Quality Improvement Program databases to identify patients with LEPT.

How Health Systems World-wide Fail Type 2 Diabetics.

For over 50 years, health systems the world over have failed people with type 2 diabetes mellitus (T2DM). The WHO documents a quadrupling of people with diabetes in a 34-year period to 422 million in 2014, the overwhelming majority of whom were T2DM. This happened despite extensive scientific literature on the causes of, as well as proven treatments for, this disease.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.