Early Change in C-Reactive Protein and Venous Thromboembolism in Patients Treated With Immune Checkpoint Inhibitors.

Background: Patients with cancer treated with immune-checkpoint inhibitors (ICIs) have a substantial risk of venous thromboembolism (VTE). The association between ICI-induced inflammation and hypercoagulability is unclear, and no biomarkers currently exist to stratify VTE risk.

Objectives: The authors sought to determine the association between the early changes in C-reactive protein (CRP) after ICI initiation and the risk of VTE.

Oxytocin: Not "just a female hormone": A very special issue and a very special molecule.

For decades it was believed that oxytocin was "just a female hormone." This was a mistake. In the 21st century it has become clear that oxytocin arose from ancient roots, and acquired dozens of diverse functions throughout the mammalian body.

Multimodality Imaging Evaluation of Diseases of the Pulmonic Valve and Right Ventricular Outflow Tract for the Adult Cardiologist.

Disorders of the pulmonic valve (PV) receive considerably less attention than other forms of valvular heart disease. Due to the dramatically improved survival of children with congenital heart disease over the last 5 decades, there has been a steady increase in the prevalence of adults with congenital heart disease, which necessitates that clinicians become familiar with the anatomy and the evaluation of right ventricular outflow tract and PV anomalies. A multimodality imaging approach using echocardiography, cardiac computed tomography, and magnetic resonance imaging is essential for a comprehensive evaluation of the anatomy and function of the right ventricular outflow tract, PV, and supravalvular region.

Afferent Projections to the Calca/CGRP-Expressing Parabrachial Neurons in Mice.

The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons that regulate responses to a variety of interoceptive and cutaneous sensory signals. One lateral PB subpopulation expresses the Calca gene, which codes for the neuropeptide calcitonin gene-related peptide (CGRP). These PB neurons relay signals related to threatening stimuli such as hypercarbia, pain, and nausea, yet their inputs and their neurochemical identity are only partially understood.

Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL/6 Substrains.

Opioid use disorder is heritable, yet its genetic etiology is largely unknown. C57BL/6J and C57BL/6NJ mouse substrains exhibit phenotypic diversity in the context of limited genetic diversity which together can facilitate genetic discovery. Here, we found C57BL/6NJ mice were less sensitive to oxycodone (OXY)-induced locomotor activation versus C57BL/6J mice in a conditioned place preference paradigm.

How Much Pain Medication Do Patients Require After Posterior Iliac Crest Bone Graft to the Alveolar Cleft?

Objective: The purpose of this study was to quantify analgesic use following alveolar cleft bone grafting (ABG) utilizing a posterior iliac crest (PIC) donor site.

Design: This is a prospective cohort study of consecutive patients that underwent ABG with PIC in a 10 month period from November 2022 to September 2023.

Setting: Tertiary care free-standing pediatric hospital.

Overview of Molecular Prognostication for Common Solid Tumor Histologies - What the Surgeon Should Know.

Study Design: Narrative Literature review.

Objective: To provide a general overview of important molecular markers and targeted therapies for the most common neoplasms (lung, breast, prostate and melanoma) that metastasize to the spine and offer guidance on how to best incorporate them in the clinical setting.

Methods: A narrative review of the literature was performed using PubMed, Google Scholar, Medline databases, as well as the histology-specific National Comprehensive Cancer Network guidelines to identify relevant articles limited to the English language.

A Critical Appraisal of the Application of Frailty and Sarcopenia in the Spinal Oncology Population.

Study Design: Systematic review and clinimetric analysis.

Objectives: Frailty and sarcopenia predict worse surgical outcomes among spinal degenerative and deformity-related populations; this association is less clear in the context of spinal oncology. Here, we sought to identify frailty and sarcopenia tools applied in spinal oncology and appraise their clinimetric properties.

Prevention and Management of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review of Available Evidence and Proposed Clinical Decision-Making Algorithm.

Study Design: Narrative Review.

Objective: Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population.

What is the Optimal Management of Metastatic Spine Patients With Intermediate Spinal Instability Neoplastic Scores: To Operate or Not to Operate?

Study Design: Systematic review.

Objective: In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries.

Methods: Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery.

Role of Posterior Carbon Fiber Implants in Spine Tumor Surgery.

Study Design: Narrative Review.

Objective: The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability.

Discovery of FHD-286, a First-in-Class, Orally Bioavailable, Allosteric Dual Inhibitor of the Brahma Homologue (BRM) and Brahma-Related Gene 1 (BRG1) ATPase Activity for the Treatment of SWItch/Sucrose Non-Fermentable (SWI/SNF) Dependent Cancers.

BRM (SMARCA2) and BRG1 (SMARCA4) are mutually exclusive ATPase subunits of the mSWI/SNF (BAF) chromatin remodeling complex. BAF is an attractive therapeutic target because of its role in transcription, and mutations in the subunits of BAF are common in cancer and neurological disorders. Herein, we report the discovery of compound () as a potent allosteric inhibitor of the dual ATPase subunits from a high-throughput screening hit with a BRM IC of ∼27 μM.

Dual Strategies Based on Golgi Apparatus/Endoplasmic Reticulum Targeting and Anchoring for High-Efficiency siRNA Delivery and Tumor RNAi Therapy.

Endolysosomal degradation of small interfering RNA (siRNA) significantly reduces the efficacy of RNA interference (RNAi) delivered by nonviral systems. Leveraging Golgi apparatus/endoplasmic reticulum (Golgi/ER) transport can help siRNA bypass the endolysosomal degradation pathway, but this approach may also result in insufficient siRNA release and an increased risk of Golgi/ER-mediated exocytosis. To address these challenges, we developed two distinct strategies using a nanocomplex of cell-penetrating poly(disulfide)s and chondroitin sulfate, which enhances targeted internalization, Golgi transport, and rapid cytoplasmic release of loaded siRNA.

Exploring the Impact of Minor Water Content on Polymer Electrolytes with Molecular Dynamics.

Solid-state polymer electrolytes (SPEs) are increasingly favored over liquid electrolytes for emerging energy storage devices due to their safety features, enhanced stability, and multifunctionality. Minor solvents (such as water) are often introduced unintentionally or intentionally into SPEs. Although it can significantly affect SPEs' electrochemical and mechanical properties, the fundamental role of such solvent content has rarely been studied.

Insurance gaps at age-19 and age-26 health insurance eligibility thresholds by childhood-onset condition severity, Colorado 2014-2018.

Objective: To characterize health insurance gap patterns related to age-19 Medicaid and age-26 commercial age-eligibility cutoffs.

Study Setting And Design: This descriptive analysis spans 2014-2018, after Affordable Care Act implementation, but before COVID-19 emergency provisions. We defined insurance gaps as ≥3 consecutive months without observed enrollment, preceded and followed by ≥1 month of enrollment and stratified results by insurance source and clinical severity (e.

Environmental Risk Factors for Systemic Lupus Erythematosus through the Lens of Social Determinants of Health.

Systemic lupus erythematosus (SLE) is a serious multisystem autoimmune disease, marked by alarming sociodemographic inequities. In the U.S.

Pacific Northwest native plants and native cultivars, part I: pollinator visitation.

Planting native flora is a popular conservation strategy for pollinators. When searching for native plants, consumers may encounter cultivars of native plants, which can have different phenotypic traits than plants found in wild populations ("wild-type native plants"). Previous research evaluating pollinator visitation to wild-type native plants and native cultivars has yielded mixed results, in terms of whether their visitation rates are similar or distinct.

Impact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research.

Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Long-term Outcomes of Definitive Chemoradiation with Proton Therapy for Treatment of Carcinoma of the Anal Canal: Combined Analysis of Two Prospective Trials.

Purpose/objective(s): While definitive chemoradiation (CRT) with 5-FU/MMC remains the standard of care for localized anal cancer, treatment is associated with significant acute and late toxicity. Proton radiation therapy (RT) may potentially reduce such toxicity. Here, we assess the long-term outcomes of anal cancer patients treated with CRT using proton RT in two prospective pilot studies.