Same-Slide Spatial Multi-Omics Integration Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment.

The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization to provide systems-level understanding of diseases. Both technologies currently remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex, spatial resolution, and analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms.

SARS-CoV-2 infection of salivary glands compromises the production of a secreted antifungal peptide with potential implications for development of oral candidiasis.

Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen Candida albicans. Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation.

Cell therapy for a rare disease- hairy cell leukemia variant.

Hairy cell leukemia variant (HCL-v) is a rare malignancy of clonal mature B-cells that follows a chronic disease course. HCL-v patients are often resistant to purine nucleoside analogs, which are the first-line therapy. To address the shortcomings of current therapy for HCL-v, we investigated the activity of a BAFF ligand-based CAR-T cell which binds to all three BAFF receptors, BAFF-receptor, TACI, and BCMA.

The AD3 locus of synaptotagmin-1 C2 domains modulates domain stability.

Synaptotagmin-1 (syt1) functions as the Ca-dependent sensor that triggers the rapid and synchronous release of neurotransmitters from neurotransmitter-containing vesicles during neuronal exocytosis. The syt1 protein has two homologous tandem C2 domains that interact with phospholipids in a Ca-dependent manner. Despite the crucial role of syt1 in exocytosis, the precise interactions between Ca, syt1, and phospholipids are not fully understood.

Communities That HEAL Intervention and Mortality Including Polysubstance Overdose Deaths: A Randomized Clinical Trial.

Importance: The HEALing Communities Study (HCS) evaluated the effectiveness of the Communities That HEAL (CTH) intervention in preventing fatal overdoses amidst the US opioid epidemic.

Objective: To evaluate the impact of the CTH intervention on total drug overdose deaths and overdose deaths involving combinations of opioids with psychostimulants or benzodiazepines.

Design, Setting, And Participants: This randomized clinical trial was a parallel-arm, multisite, community-randomized, open, and waitlisted controlled comparison trial of communities in 4 US states between 2020 and 2023.

Lessons Learned From Developing Dashboards to Support Decision-Making for Community Opioid Response by Community Stakeholders: Mixed Methods and Multisite Study.

Background: Data dashboards are published tools that present visualizations; they are increasingly used to display data about behavioral health, social determinants of health, and chronic and infectious disease risks to inform or support public health endeavors. Dashboards can be an evidence-based approach used by communities to influence decision-making in health care for specific populations. Despite widespread use, evidence on how to best design and use dashboards in the public health realm is limited.

High-throughput sequencing of archival cerebrospinal fluid specimens defines B-lymphoblastic leukemia clonal composition.

Detailed characterization of the B-lymphoblastic leukemia (B-ALL) cells which invade the central nervous system (CNS) has been limited by practical challenges. To test whether the clonal composition of the cerebrospinal fluid (CSF) reflects the primary B-ALL tissue, we applied immunoglobulin (Ig) high-throughput sequencing (HTS) of archival CSF cytospin preparations from six patients with morphologically defined CNS involvement. We discovered that most CSF clones are detectable at some timepoint in the primary tissue, but that shifting clonal abundance is prevalent across tissue sites between diagnosis and relapse.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.

SARS-CoV-2 Infection of Salivary Glands Compromises Oral Antifungal Innate Immunity and Predisposes to Oral Candidiasis.

Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen . Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation.

Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

Background: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes.

Nasal Intubation is not Associated with "Smoother" Emergence from General Anesthesia for Carotid Endarterectomy: A Case-Cohort Study.

Background: Postoperative hematoma after carotid endarterectomy (CEA) is a devastating complication and may be more likely in patients with uncontrolled hypertension and coughing on emergence from anesthesia. We sought to determine if intubation with a nasal endotracheal tube (ETT)-instead of an oral ETT-is associated with "smoother" (i.e.

Examination of naloxone dosing patterns for opioid overdose by emergency medical services in Kentucky during increased fentanyl use from 2018 to 2021.

Background: Fatal overdoses involving fentanyl/fentanyl analogs (F/FA) have increased in the US, raising questions about naloxone doses for F/FA overdose reversal. Emergency medical services (EMS) data provide an opportunity to examine naloxone administration changes as fentanyl increases in the illicit opioid supply.

Methods: Administered naloxone intranasal-equivalent total dose (INTD) in milligrams (mg) was calculated for Kentucky EMS suspected opioid overdose (SOO) encounters (n=33,846), 2018-2021, and patterns of administration were examined.

Drug disposal deserts: An assessment of receptacle availability in Kentucky community pharmacies.

Purpose: The purpose of this study was to describe the county-level availability of drug disposal receptacles in Kentucky community pharmacies and show the relationship between installed receptacles and opioid analgesic (OA)/controlled substance dispensing rates, stratifying where possible by urban-rural classification.

Methods: Using 2020 data from the Kentucky All Schedule Prescription Electronic Reporting program and disposal receptacle data from the US Drug Enforcement Agency, county-level comparisons were made between number of receptacles and OA/controlled substance dispensing rates. Logistic and negative binomial regression models were used to assess for differences between rural/urban county designation and odds of ≥1 disposal receptacle and compare the rates of receptacles per dispensed OA dose in rural/urban counties.

Spatial access to buprenorphine-waivered prescribers in the HEALing communities study: Enhanced 2-step floating catchment area analyses in Massachusetts, Ohio, and Kentucky.

Introduction: The opioid overdose epidemic continues to impact a large swath of the population in the US. Medications for opioid use disorders (MOUD) are an effective resource to combat the epidemic; however, there is limited research on MOUD treatment access that accounts for both supply of and demand for services. We aimed to examine access to buprenorphine prescribers in the HEALing Communities Study (HCS) Wave 2 communities in Massachusetts, Ohio, and Kentucky during 2021, and the association between buprenorphine access and opioid-related incidents, specifically fatal overdoses and opioid-related responses by emergency medical services (EMS).

Sustained Implementation of an Evidence-Based Extubation Checklist Reduced Extubation Failure in Trauma Patients.

Extubation failure remains a challenge in the perioperative setting. The aim of this intervention was to decrease the rate of perioperative extubation failure through the utilization of an extubation checklist. A five-item evidence-based extubation readiness checklist was implemented at a level I trauma center on all patients who were electively extubated in the operating room (OR).

Early Guided Palliative Care Communication for Patients With COVID-19 Receiving ECMO.

Background: Extracorporeal membrane oxygenation (ECMO) combined with COVID-19 presents challenges (eg, isolation, anticipatory grief) for patients and families.

Objective: To (1) describe characteristics and outcomes of patients with COVID-19 receiving ECMO, (2) develop a practice improvement strategy to implement early, semistructured palliative care communication in ECMO acknowledgment meetings with patients' families, and (3) examine family members' experiences as recorded in clinicians' notes during these meetings.

Methods: Descriptive observation of guided, in-depth meetings with families of patients with COVID-19 receiving ECMO, as gathered from the electronic medical record of a large urban academic medical center.

Impact of Pandemic Response on Training Experience of Anesthesiology Residents in an Academic Medical Center: A Retrospective Cohort Study.

Background The impact of the coronavirus disease 2019 (COVID-19) pandemic substantially altered operations at hospitals that support graduate medical education. We examined the impact of the pandemic on an anesthesiology training program with respect to overall case volume, subspecialty exposure, procedural skill experience, and approaches to airway management. Methods Data for this single center, retrospective cohort study came from an Institutional Review Board approved repository for clinical data.

Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance.

Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups.

Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention.

Temporal variations in the level of chlordecone in seawater and marine organisms in Martinique Island (Lesser Antilles).

The present study, conducted in the Galion Bay in Martinique, aims to highlight the temporal and seasonal variations of chlordecone contamination (an organochlorine pollutant) in the ambient environment (seawater) and also in the marine organisms in three main coastal marine habitats (mangroves, seagrass beds and coral reefs). To this end, two methodologies were used to measure and compare the chemical contamination of seawater during 13 months (spot samplings and POCIS technique). In parallel, concentrations of chlordecone and isotopic ratios (C and N) were carried out on marine organisms, collected during two contrasting climatic periods (dry and rainy), to evidence seasonal variations.