A-synuclein prion strains differentially adapt after passage in mice.

In patients with synucleinopathies, the protein α-synuclein misfolds into multiple conformations, each of which determines whether a patient develops multiple system atrophy (MSA) or one of three Lewy body diseases (LBDs). However, patients may also first present with pure autonomic failure, which strictly impacts autonomic nerves in the periphery, which can then phenoconvert into MSA or a LBD. When neuroinvasion happens, it remains unknown if strain properties are retained or if strain adaptation occurs, even though neuroinvasion of some prion protein (PrP) strains is known to result in the emergence of novel PrP strain variants.

A novel approach to research engagement: Developing a targeted theory of change with Black and African-American stakeholders.

Purpose: Community inclusion in research may increase the quality and relevance of research, but doing so in an equitable way is complex. Novel approaches used to build engagement with historically marginalized communities in other sectors may have relevance in the clinical research sector.

Method: To address long-standing gaps and challenges, a stakeholder group was convened to develop a theory of change (ToC), a structured method for obtaining input from stakeholders to enhance the design, conduct, and dissemination of research.

An Exploratory Analysis of ChatGPT Compared to Human Performance With the Anesthesiology Oral Board Examination: Initial Insights and Implications.

Background: Chat Generative Pre-Trained Transformer (ChatGPT) has been tested and has passed various high-level examinations. However, it has not been tested on an examination such as the American Board of Anesthesiology (ABA) Standardized Oral Examination (SOE). The SOE is designed to assess higher-level competencies, such as judgment, organization, adaptability to unexpected clinical changes, and presentation of information.

Fostering Inclusivity in Research Engagement for Underrepresented Populations in Parkinson's Disease: The FIRE-UP PD study.

Background: Members of vulnerable populations are underrepresented in Parkinson's disease (PD) research. A complex web of research barriers perpetuates this gap. Community-based research methods are one approach to addressing this issue.

Do Surgical Smoke Evacuators Increase the Risk of Hearing Loss for Operative Personnel During Routine Adenotonsillectomy Surgery?

Introduction: Aerosol mitigation equipment implemented due to COVID-19 has increased noise levels in the operating room (OR) during otolaryngological procedures. Intraoperative sound levels may potentially place personnel at risk for occupational hearing loss. This study hypothesized that cumulative intraoperative noise exposures with aerosol mitigation equipment exceed recommended occupational noise exposure levels.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

Background: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth.

Methods: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system.

High Prevalence of Obstructive Sleep-Disordered Breathing in Pediatric Patients With Turner Syndrome.

Objective: Girls with Turner syndrome (TS) often have features that have been associated with obstructive sleep-disordered breathing (oSDB). However, little is known about oSDB in TS. Herein, we aimed to characterize oSDB in young patients with TS and identify associated risk factors.

Effect of Perioperative Antithrombotics on Postoperative Transfusion and Hematoma in Head and Neck Free Flaps.

Objective: To explore if antiplatelet or anticoagulant therapy increases the risk of transfusion requirement or postoperative hematoma formation in patients undergoing microvascular reconstruction for head and neck defects.

Study Design: Retrospective cohort study.

Setting: Departments of Otolaryngology-Head and Neck Surgery at the University of Alabama at Birmingham, the University of Colorado, and the University of California Irvine.

Selective targeting of IL2Rβγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC.

The implementation of cancer immunotherapies has seen limited clinical success in head and neck squamous cell carcinoma (HNSCC). Interleukin-2 (IL-2), which modulates the survival and functionality of lymphocytes, is an attractive target for new immunotherapies but one that is limited by presence of regulatory T cells (Tregs) expressing the high-affinity IL-2Rα. The bispecific immunocytokine PD1-IL2v preferentially delivers IL-2 signaling through IL-2Rβγ on PD-1-expressing cells.

Discovery of Antimicrobial Phosphonopeptide Natural Products from Bacillus velezensis by Genome Mining.

Phosphonate natural products are renowned for inhibitory activities which underly their development as antibiotics and pesticides. Although most phosphonate natural products have been isolated from , bioinformatic surveys suggest that many other bacterial genera are replete with similar biosynthetic potential. While mining actinobacterial genomes, we encountered a contaminated data set which included a biosynthetic gene cluster predicted to produce novel phosphonate compounds.

Electrochemical Lipolysis Induces Adipocyte Death and Fat Necrosis: In Vivo Pilot Study in Pigs.

Background: Current minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars.

Simultaneous targeting of PD-1 and IL-2Rβγ with radiation therapy inhibits pancreatic cancer growth and metastasis.

In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL-2Rβ and IL-2Rγ along with decreased IL-2Rα expression. The bispecific PD1-IL2v is a PD-1-targeted IL-2 variant (IL-2v) immunocytokine with engineered IL-2 cis targeted to PD-1 and abolished IL-2Rα binding, which enhances tumor-antigen-specific T cell activation while reducing regulatory T cell (Treg) suppression. Using PD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival, along with a profound increase in tumor-infiltrating CD8 T cell subsets with a transcriptionally and metabolically active phenotype and preferential activation of antigen-specific CD8 T cells.

Promising Implants in Rhinoplasty.

Many dilemmas in rhinoplasty tempt surgeons to use exogenous materials. We have long looked toward implants to decrease operative time, to achieve a more reliable result, or when there is a paucity of autologous material. More than ever, the innovative and highly lucrative field of is developing technologically advanced products.

Incidental Meckel's Diverticulum With Neuroendocrine Tumor.

Meckel's diverticulum (MD), the most common congenital disease of the small bowel, commonly presents with symptoms of painless rectal bleeding and intestinal obstruction. The treatment of symptomatic MD involves resection of the lesion regardless of patient age; however, the excision of asymptomatic and incidentally identified MDs in adults remain controversial. On one hand, the complications arising from MDs decrease with age, leading to a lower benefit than risk ratio with prophylactic resection.

Visualization of ex vivo rabbit olfactory mucosa and foramina with three-dimensional optical coherence tomography.

There is increasing interest in developing a minimally invasive imaging modality to safely evaluate dynamic microscopic changes of the olfactory mucosa and cribriform foramina. Herein, we utilized three-dimensional (3D) optical coherence tomography (OCT) to characterize the ex vivo stratified substructure of olfactory mucosa in rabbits and create 3D reconstructed images of olfactory foramina. Olfactory mucosa and cribriform plates from four New Zealand White rabbits were dissected and imaged using two swept-source OCT systems: (1) 1.

Valinophos Reveals a New Route in Microbial Phosphonate Biosynthesis That Is Broadly Conserved in Nature.

Phosphonate natural products are potent inhibitors of cellular metabolism with an established record of commercialization in medicine and biotechnology. Although genome mining has emerged as an accelerated method for the discovery of new phosphonates, a robust framework of their metabolism is needed to identify the pathways most likely to yield compounds with desired activities. Here we expand our understanding of these natural products by reporting the complete biosynthetic pathway for valinophos, a phosphonopeptide natural product containing the unusual ()-2,3-dihydroxypropylphosphonate (DHPPA) scaffold.

Biosynthesis of Argolaphos Illuminates the Unusual Biochemical Origins of Aminomethylphosphonate and N-Hydroxyarginine Containing Natural Products.

Phosphonate natural products have a history of successful application in medicine and biotechnology due to their ability to inhibit essential cellular pathways. This has inspired efforts to discover phosphonate natural products by prioritizing microbial strains whose genomes encode uncharacterized biosynthetic gene clusters (BGCs). Thus, success in genome mining is dependent on establishing the fundamental principles underlying the biosynthesis of inhibitory chemical moieties to facilitate accurate prediction of BGCs and the bioactivities of their products.

Multimodality Management of EBV-Associated Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a rare cancer of the nasopharyngeal mucosa with a specific geographic predisposition. NPC is often associated with Epstein-Barr Virus (EBV) infection and as a result contains many characteristic biomarkers. Treatment of locally-contained NPC is generally achieved through use of radiotherapy (RT), as part of a multimodality treatment regimen.

Mind-Body Therapies for Cancer Patients Living with Depression, Anxiety or Insomnia (MIRACLE): A Systematic Review with Individual Participant Data Network Meta-Analysis.

Depression, anxiety, and insomnia are common in cancer patients. Mind-body therapies (MBTs) are promising forms of treatment for cancer patients living with depression, anxiety, and insomnia. The objective of this study is to assess the effectiveness and acceptability of MBTs in cancer patients living with depression, anxiety, or insomnia.

Exploring feedback-controlled versus open-circuit electrochemical lipolysis in ex vivo and in vivo porcine fat: A feasibility study.

Objectives: Minimally invasive fat sculpting techniques are becoming more widespread with the development of office-based devices and therapies. Electrochemical lipolysis (ECLL) is a needle-based technology that uses direct current (DC) to electrolyze tissue water creating acid and base in situ. In turn, fat is saponified and adipocyte cell membrane lysis occurs.

Electrochemical treatment of ex vivo human abdominal skin and potential use in scar management: A pilot study.

Introduction: Scar treatments aim to address pathologic collagen deposition; however, they can be expensive or difficult to control. Electrochemical therapy (ECT) offers a simple alternative treatment. The purpose of this study is to examine the acid-base and histological changes in ex vivo human abdominal skin following ECT.