Lewy body diseases and the gut.

Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.

Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy that necessitates the identification of novel therapeutic strategies. Here, we report that intracellular levels of very long chain fatty acids (VLCFAs) control the cytotoxicity of MM chemotherapeutic agents. Inhibition of VLCFA biosynthesis reduced cell death in MM cells caused by the proteasome inhibitor, bortezomib.

Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity.

Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we identified and characterized Rh05, Rh152/151 and Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one of these proteins displays functional similarities to their prospective HCMV orthologs with respect to antagonizing host FcγR activation in vitro.

Stress Cardiac Magnetic Resonance Imaging in Intermediate-Risk Emergency Department Patients with Abnormal High-Sensitivity Troponin.

Background: Patients presenting to the emergency department (ED) with chest pain often have abnormal high-sensitivity troponin (hsTn). However, only about 5% have an acute coronary syndrome. We aimed to assess the safety, feasibility and utility of a clinical disposition protocol including outpatient observation with stress cardiac-magnetic-resonance (CMR) in intermediate-risk patients with abnormal hsTn of unclear etiology.

A model of care redesign within rheumatology: A mixed methods approach integrating nurse practitioners and physician assistants.

Background: Increasing patient demand and clinician burnout in rheumatology practices have highlighted the need for more efficient models of care (MOC). Interprofessional collaboration is essential for improving patient outcomes and clinician satisfaction.

Local Problem: Our current MOC lacks standardization and formal integration of Nurse Practitioners (NPs) and Physician Assistants (PAs), resulting in reduced clinician satisfaction and limited patient access.

Assessing the threat of harboring a multi-resistant IncC plasmid and the efficacy of an antibiotic targeting LpxC.

Self-transmissible IncC plasmids rapidly spread multidrug resistance in many medically important pathogens worldwide. A large plasmid of this type (pIP1202, ~80 Kb) has been isolated in a clinical isolate of , the agent of plague. Here, we report that pIP1202 was highly stable in infected mice and fleas and did not reduce virulence in these animals.

Emergent Carotid Stenting During Thrombectomy in Tandem Occlusions Secondary to Dissection: A STOP-CAD Secondary Study.

The optimal endovascular management of cervical carotid dissection causing tandem occlusion remains uncertain. We investigated the impact of emergent carotid stenting during endovascular treatment (EVT) for acute ischemic stroke (AIS) in patients with tandem occlusion secondary to cervical carotid artery dissection. This was a secondary analysis of patients treated with EVT for AIS due to occlusive carotid artery dissection and tandem occlusion included in the retrospective international Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD) study.

Modern perspective of the Rice Diet for hypertension and other metabolic diseases.

Background: In the early 1940s, before antihypertensive drugs were available, the Rice Diet Programme (RDP) was developed to treat severe hypertension and, later, diabetes and obesity. Despite significant advancements in dietary management for these conditions since then, debates remain regarding the proper guidelines for sodium and macronutrients intakes. The patient care records of RDP offer a unique source of longitudinal examination of a very low sodium (<10 mmol/day), fat, cholesterol and protein diet on blood pressure (BP), other health markers and survival.

Unraveling Histiocytic Disorders: Two Cases From Resource-Limited Settings.

Histiocytic disorders include a range of uncommon illnesses marked by the buildup of cells that have developed into macrophages, dendritic cells, or monocytes in diverse tissues and organs. Over 100 distinct subtypes have been documented, exhibiting a diverse array of clinical symptoms, presentations, and histologic features that can be confused with other clinical conditions leading to delayed diagnosis. They affect both children and adults, generating a variety of clinical symptoms that can be limited to one position, numerous areas within one system, or affect many systems in the body.

Cognitive Outcomes After Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression: Résultats cognitifs après la stimulation magnétique transcrânienne pour le traitement de la dépression chez les personnes âgées.

Background: Late-life depression (LLD) is often accompanied by cognitive impairment, which may persist despite antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) is an efficacious treatment for depression, with potential benefits on cognitive functioning. However, research on cognitive effects is inconclusive, relatively sparse in LLD, and predominantly focused on group-level cognitive changes.

Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry.

Three-dimensional diffractive acoustic tomography.

Acoustically probing biological tissues with light or sound, photoacoustic and ultrasound imaging can provide anatomical, functional, and/or molecular information at depths far beyond the optical diffusion limit. However, most photoacoustic and ultrasound imaging systems rely on linear-array transducers with elevational focusing and are limited to two-dimensional imaging with anisotropic resolutions. Here, we present three-dimensional diffractive acoustic tomography (3D-DAT), which uses an off-the-shelf linear-array transducer with single-slit acoustic diffraction.

Social mixing patterns of United States healthcare personnel at a quaternary health center: a prospective observational study.

Background: Understanding healthcare personnel's (HCP) contact patterns are important to mitigate healthcare-associated infectious disease transmission. Little is known about how HCP contact patterns change over time or during outbreaks such as the COVID-19 pandemic.

Methods: This study in a large United States healthcare system examined the social contact patterns of HCP via standardized social contact diaries.

Barriers and facilitators to global access to life-saving skills training: an international cross-sectional survey.

Introduction: Emergency care begins in the community, who are often the first on the scene. Where emergency care systems are nascent or absent, bystanders represent the only prehospital emergency care that victims might receive. It is important to equip bystanders through life-saving skills training (LST).

FLASH proton reirradiation, with or without hypofractionation, reduces chronic toxicity in the normal murine intestine, skin, and bone.

Background And Purpose: The normal tissue sparing afforded by FLASH radiotherapy is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton radiotherapy (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated.

Impact of continuous positive airway pressure therapy on restless legs syndrome in patients with coexistent obstructive sleep apnea: A qualitative systematic review.

Introduction: Obstructive sleep apnea (OSA) is characterized by repetitive episodes of complete or partial upper airway collapse during sleep. Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an uncomfortable urge to move the legs, especially during inactivity and evenings. Both OSA and RLS are common with significant overlap: RLS is present in up to 36% of those with OSA.

Concepts of Suffering at the End of Life Amongst Emergency, Palliative Care and Geriatric Medicine Physicians in Malaysia.

Background: Palliative Care, Geriatrics and Emergency physicians are exposed to death, terminally ill patients and distress of patients and their families. As physicians bear witness to patients' suffering, they are vulnerable to the costs of caring-the emotional distress associated with providing compassionate and empathetic care to patients. If left unattended, this may culminate in burnout and compromise professional identity.

Multi-diagnostic chest-worn patch to detect obstructive sleep apnea and cardiac arrhythmias.

Study Objectives: Evaluate the performance of the SANSA device to simultaneously assess obstructive sleep apnea (OSA) and cardiac arrhythmias.

Methods: Participants suspected or known to have OSA underwent polysomnography (PSG) while wearing SANSA. SANSA's algorithm was trained using 86 records and tested on 67 to evaluate training bias.

Comparison of in-clinic assessment of 6MWT by conventional method and using wearable sensors for patients with ATTR-CM.

Introduction: The 6-minute walk test (6MWT) is used to assess submaximal exercise capacity in clinical trials. Conducting the 6MWT can be challenging when patients cannot visit the clinic due to physical/travel limitations. This pilot study assessed the feasibility of conducting the 6MWT using wearable sensors for patients with transthyretin amyloid cardiomyopathy.

ALS Motor Observational Telemedicine Objective Rasch-Built Assessment: A Quantitative Scale for the Era of Teleneurology.

Background And Objectives: Telemedicine has become a mainstay of ALS clinical care, but there is currently no standardized approach for assessing and tracking changes to the neurologic examination in this format. The goal of this study was to create a standardized telemedicine-based motor examination scale to objectively and reliably track ALS progression and use Rasch methodology to validate the scale and improve its psychometric properties.

Methods: A draft telemedicine examination scale with 25 items assessing movement in the bulbar muscles, neck, trunk, and extremities was created by an ALS expert panel, incorporating input from patient advisors.

SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.

CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Unlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.