A Case of Xylazine-Induced Necrotic Skin Ulcerations in an IV-Drug User in Florida.

Introduction: As illicit drug manufacturers find new ways to market their products and increase their profit margins, multiple contaminants have found their way into the illicit drug supply. The newest addition, xylazine, also known as "tranq," has spread through the city of Philadelphia and has recently been gaining ground across the United States, including in the state of Florida.

Case Presentation: This case describes a 37-year-old male with a significant past psychiatric history of severe polysubstance intravenous (IV) use, including fentanyl and methamphetamine.

Estimating the CTDI with helical acquisitions: Results from a national generalizability study.

Background: While many clinical computed tomography (CT) protocols use helical scanning, the traditional method for measuring the volume CT Dose Index (CTDI) requires modifying the helical protocol to perform a single axial rotation. This modification can present challenges and mismatched settings across various scanner models.

Purpose: This study investigates the generalizability of a helical methodology for estimating CTDI across a diverse range of participants, CT scanner models, and protocol parameters.

Dual CD47 and PD-L1 blockade elicits anti-tumor immunity by intratumoral CD8 T cells.

Objectives: Bispecific antibodies targeting CD47 and PD-L1 (CD47 × PD-L1 BisAb) demonstrate efficacy against a range of solid cancers. While dual blockade negates anti-CD47-mediated toxicity, the effect of combined innate and adaptive immune activation on protective tumor-resident CD8 T cells has yet to be fully elucidated.

Methods: CD8 T cell populations were tracked upon CD47 × PD-L1 BisAb treatment in an orthotopic model of murine breast cancer where anti-tumor immunity is mediated by CD8 T cells.

A Tumor Homing Peptide-Linked Arsenic Compound Inhibits Pancreatic Cancer Growth and Enhances the Inhibitory Effect of Gemcitabine.

Arsenic trioxide (ATO) has been shown to inhibit pancreatic cancer (PC) cell growth and to promote the inhibitory effects of gemcitabine (Gem) on PC . However, the high toxicity of ATO associated with the required high doses and indiscriminate targeting has limited its clinical application. This study aimed to determine whether coupling arsenic to a tumor homing peptide would increase the inhibitory potency against PC cells.

Discovery of reversible and covalent TEAD 1 selective inhibitors MSC-1254 and MSC-5046 based on one scaffold.

The Transcriptional Enhanced Associated Domain (TEAD) family of transcription factors are key components of the Hippo signalling family which play a crucial role in the regulation of cell proliferation, differentiation and apoptosis. The identification of inhibitors of the TEAD transcription factors are an attractive strategy for the development of novel anticancer therapies. A HTS campaign identified hit 1, which was optimised using structure-based drug design, to deliver potent TEAD1 selective inhibitors with both a reversible and covalent mode of inhibition.

Effect of substituents on the ability of nickel Schiff base complexes with four pendant groups to bind to G-quadruplexes.

The synthesis of eleven new nickel Schiff base complexes each bearing four pendant groups is reported. The structures of the complexes differ in the identity of the pendant groups and/or diamine moiety. All complexes were characterised by microanalysis, Nuclear Magnetic Resonance (NMR) spectroscopy and Electrospray Ionisation Mass Spectrometry (ESI-MS), while the solid-state structures of two of the molecules were also determined using X-ray crystallographic methods.

Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol.

Objective: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented.

Outcome Evaluation of a Public Health Intervention on Cardiovascular Disease (CVD) Prevention Among Women Aged 40-64 with Low Incomes in Nebraska.

Objectives: To evaluate the effectiveness of the program interventions on cardiovascular disease in Nebraska women who are low income and have no health insurance.

Design: This evaluation used pre- and post-comparison approach. Paired t test and McNemar's test were used to examine the changes after the program interventions.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation.

Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy.

Tyvaso DPI: Drug-device characteristics and patient clinical considerations.

Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It is approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. Tyvaso DPI utilizes single-use prefilled cartridges to ensure proper dosing.

Maternal and Neonatal Outcomes of Adolescent Pregnancies in the Military Health System.

Objective: To determine if universal access to care for military beneficiaries improves timing of presentation to prenatal care (PNC) in adolescent and young adult (AYA) pregnancies, improving maternal and neonatal outcomes.

Study Design: Retrospective descriptive cohort study, which assessed PNC initiation in eligible military beneficiaries: dependent daughters, active-duty women, and active-duty spouses aged 13 to 26 between January 2015 and December 2019, and subsequent adverse maternal and neonatal outcomes.

Results: The cohort included 4,557 eligible pregnancies and 4,044 mothers aged 13 to 26.

Optimizing Arsenic Therapy by Selectively Targeting Leukemia Cells.

Arsenic, in the simple form of arsenic trioxide, is currently marketed for the treatment of acute promyelocytic leukemia. Due to the multifaceted mechanisms of action of arsenic, it has also shown promise in other types of leukemias but is hindered by its toxic effects toward normal cells. This research has aimed to determine whether tumor-homing peptide complexes of arsenic can be designed and developed to strategically target specific cancers.

Inflammatory Bowel Disease Prevalence: Surveillance data from the U.S. National Health and Nutrition Examination Survey.

Determining the overall US prevalence of Inflammatory Bowel Disease (IBD) is essential to national level prevention programs and population risk assessment; however currently US IBD prevalence remains uncertain. We used US National Health and Nutrition Examination Survey (NHANES) data to estimate the population-based prevalence of a self-reported history of medically diagnosed IBD, comparing to prior reports. Lifetime IBD prevalence for adults aged 20 + years was estimated in the independently conducted NHANES II (1976-80) and NHANES 2009-10 surveys.

Optimal Randomization Designs for Large Multicenter Clinical Trials: From the National Institutes of Health Stroke Trials Network Funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke Experience.

From 2016 to 2021, the National Institutes of Health Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke initiated ten multicenter randomized controlled clinical trials. Optimal subject randomization designs are demanded with 4 critical properties: (1) protection of treatment assignment randomness, (2) achievement of the desired treatment allocation ratio, (3) balancing of baseline covariates, and (4) ease of implementation. For acute stroke trials, it is necessary to minimize the time between eligibility assessment and treatment initiation.

Co-designing resources to support the transition from child to adult health services for young people with cerebral palsy: A design thinking approach.

Introduction: Design thinking is a human-centred process that aims to identify the needs of end-users and iteratively develop solutions. Involving end-users in the development and design of solutions may enhance effectiveness by increasing focus on the needs of the target population. This paper describes the process of co-designing resources to support the transition from child-centred to adult-orientated health services using a design thinking approach.

Reoperation following urgent and emergent colectomy in the State of Michigan.

Background: Reoperation is associated with unfavorable outcomes and increased healthcare utilization. This study seeks to investigate the incidence and factors related to reoperation in patients undergoing urgent/emergent colectomies.

Methods: The Michigan Surgical Quality Collaborative (MSQC) database was used to identify patients undergoing urgent/emergent colectomies.

Residues forming the gating regions of asymmetric multidrug transporter Pdr5 also play roles in conformational switching and protein folding.

ATP-binding cassette (ABC) multidrug transporters are large, polytopic membrane proteins that exhibit astonishing promiscuity for their transport substrates. These transporters unidirectionally efflux thousands of structurally and functionally distinct compounds. To preclude the reentry of xenobiotic molecules via the drug-binding pocket, these proteins contain a highly conserved molecular gate, essentially allowing the transporters to function as molecular diodes.

Axial Pain and Arthritis in Diagnosed Inflammatory Bowel Disease: US National Health and Nutrition Examination Survey Data.

Objective: To estimate the nationally representative prevalence of chronic axial pain, inflammatory back pain (IBP), axial spondyloarthritis (axSpA), and peripheral arthritis in persons diagnosed with inflammatory bowel disease (IBD).

Patients And Methods: US National Health and Nutrition Examination Survey (NHANES) data from the 1976-1980 and 2009-2010 survey cycles.

Results: In NHANES 1976-1980, the chronic axial pain prevalence in participants with diagnosed ulcerative colitis (UC) was 19.

A large multi-country outbreak of monkeypox across 41 countries in the WHO European Region, 7 March to 23 August 2022.

Following the report of a non-travel-associated cluster of monkeypox cases by the United Kingdom in May 2022, 41 countries across the WHO European Region have reported 21,098 cases and two deaths by 23 August 2022. Nowcasting suggests a plateauing in case notifications. Most cases (97%) are MSM, with atypical rash-illness presentation.

Risk of Postdischarge Bleeding From Dual Antiplatelet Therapy After Percutaneous Coronary Intervention Among US Black and White Adults.

Background Dual antiplatelet therapy after percutaneous coronary intervention reduces myocardial infarctions but increases bleeding. The risk of bleeding may be higher among Black patients for unknown reasons. Bleeding risk scores have not been validated among Black patients.

Reversing Cardiac Hypertrophy at the Source Using a Cardiac Targeting Peptide Linked to miRNA106a: Targeting Genes That Cause Cardiac Hypertrophy.

Causes and treatments for heart failure (HF) have been investigated for over a century culminating in data that have led to numerous pharmacological and surgical therapies. Unfortunately, to date, even with the most current treatments, HF remains a progressive disease with no therapies targeting the cardiomyocytes directly. Technological advances within the past two to three years have brought about new paradigms for treating many diseases that previously had been extremely difficult to resolve.

The Impact of Natural Environments and Biophilic Design as Supportive and Nurturing Spaces on a Residential College Campus.

With so many college students experiencing disengagement, the physical design of a college and the connection to its natural surroundings has the potential for profound change. Natural environments, even viewing pictures of them, have the potential to positively impact parasympathetic nervous systems, increase cognitive functioning, and improve attention. This study investigated college student perceptions of their personal well-being with attention to coping, self-esteem, and physical health in a residential academic setting in the northeastern United States.