IĸBζ as a Central Modulator of Inflammatory Arthritis Pathogenesis.

Objective: Current therapies targeting individual factors in inflammatory arthritis show variable efficacy, often requiring treatment with combinations of drugs, and are associated with undesirable side effects. NF-ĸB is critical for the production and function of most inflammatory cytokines. However, given its essential role in physiologic processes, targeting NF-ĸB is precarious.

Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema.

Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair.

DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8.

Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis.

Evaluating the pediatric mental health care continuum at an American health system.

Objective: To describe trends in the pediatric mental health care continuum and identify potential gaps in care coordination.

Methods: We used electronic medical record data from October 2016 to September 2019 to characterize the prevalence of mental health issues in the pediatric population at a large American health system. This was a single institution case study.

Artificial Intelligence-Derived Electrocardiogram Assessment of Cardiac Age and Molecular Markers of Senescence in Heart Failure.

Objective: To ascertain whether heart failure (HF) itself is a senescent phenomenon independent of age, and how this is reflected at a molecular level in the circulating progenitor cell niche, and at a substrate level using a novel electrocardiogram (ECG)-based artificial intelligence platform.

Patients And Methods: Between October 14, 2016, and October 29, 2020, CD34 progenitor cells were analyzed by flow cytometry and isolated by magnetic-activated cell sorting from patients of similar age with New York Heart Association functional classes IV (n = 17) and I-II (n = 10) heart failure with reduced ejection fraction and healthy controls (n = 10). CD34 cellular senescence was quantitated by human telomerase reverse transcriptase expression and telomerase expression by quantitative polymerase chain reaction, and senescence-associated secretory phenotype (SASP) protein expression assayed in plasma.

How health systems facilitate patient-centered care and care coordination: a case series analysis to identify best practices.

Large- and small-scale transformation of healthcare delivery toward improved patient experience through promotion of patient-centered and coordinated care continues to be at the forefront of health system efforts in the United States. As part of a Quality Improvement (QI) project at a large, midwestern health system, a case series of high-performing organizations was explored with the goal of identifying best practices in patient-centered care and/or care coordination (PCC/CC). Identification of best practices was done through rapid realist review of peer-reviewed literature supporting three PCC/CC interventions per case.

Platelet-derived exosomes induce cell proliferation and wound healing in human endometrial cells.

To investigate the regenerative effects of a platelet-derived purified exosome product (PEP) on human endometrial cells. Endometrial adenocarcinoma cells (HEC-1A), endometrial stromal cells (T HESC) and menstrual blood-derived stem cells (MenSC) were assessed for exosome absorption and subsequent changes in cell proliferation and wound healing properties over 48 h. Cell proliferation increased in PEP treated T HESC (p < 0.

Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence.

Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and urethral sphincter coaptation, particularly during activities that increase intra-abdominal pressure.

Cost-effectiveness of an Emergency Department-Based Intensive Care Unit.

Importance: Value in health care is quality per unit cost (V = Q/C), and an emergency department-based intensive care unit (ED-ICU) model has been associated with improved quality. To assess the value of this care delivery model, it is essential to determine the incremental direct cost of care.

Objective: To determine the association of an ED-ICU with inflation-adjusted change in mean direct cost of care, net revenue, and direct margin per ED patient encounter.

Use of heparin to rescue immunosuppressive monocyte reprogramming by glioblastoma-derived extracellular vesicles.

Objective: The profound immunosuppression found in glioblastoma (GBM) patients is a critical barrier to effective immunotherapy. Multiple mechanisms of tumor-mediated immune suppression exist, and the induction of immunosuppressive monocytes such as myeloid-derived suppressor cells (MDSCs) is increasingly appreciated as a key part of this pathology. GBM-derived extracellular vesicles (EVs) can induce the formation of MDSCs.

Phase I trial of adjuvant mature autologous dendritic cell/allogeneic tumor lysate vaccines in combination with temozolomide in newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We previously optimized vaccine manufacture utilizing allogeneic human GBM tumor cell lysate and potent, mature autologous DCs.

Intranasal Fentanyl for On-the-Hill Analgesia by Ski Patrol.

Introduction: Intranasal fentanyl offers a means for safe and effective pain management in austere environments. Prehospital analgesia traditionally involves intravenous or intramuscular medication. However, for wilderness rescuers, these methods are often impractical.

STAT3 is a biologically relevant therapeutic target in H3K27M-mutant diffuse midline glioma.

Background: H3K27M-mutant diffuse midline glioma (DMG) is a lethal brain tumor that usually occurs in children. Despite advances in our understanding of its underlying biology, efficacious therapies are severely lacking.

Methods: We screened a library of drugs either FDA-approved or in clinical trial using a library of patient-derived H3K27M-mutant DMG cell lines with cell viability as the outcome.

A Vanishing Cecal Mass: A Rare Gastrointestinal Manifestation of Systemic Mastocytosis.

Systemic mastocytosis (SM) is a heterogeneous disease that often involves the gastrointestinal (GI) tract. Activation and accumulation of mast cells in GI organs can result in symptoms of abdominal pain, nausea and diarrhea along with organ damage with more aggressive disease. Mast cell degranulation can also result in anaphylactic reactions, which can be life-threatening.

Prehospital Supraglottic Airways: An NAEMSP Position Statement and Resource Document.

Supraglottic airway (SGA) devices provide effective conduits for oxygenation and ventilation and may offer protection from gastric aspiration. SGA devices are widely used by EMS clinicians as both rescue and primary airway management devices. While in common use for more than four decades, major developments in SGA education, science, and technology have influenced clinical strategies of SGA insertion and use in prehospital airway management for patients of all ages.

Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study.

Background: Tendons are primarily acellular, limiting their intrinsic regenerative capabilities. This limited regenerative potential contributes to delayed healing, rupture, and adhesion formation after tendon injury.

Purpose: To determine if a tendon's intrinsic regenerative potential could be improved after the application of a purified exosome product (PEP) when loaded onto a collagen scaffold.

Pediatric brain tumor cell lines exhibit miRNA-depleted, Y RNA-enriched extracellular vesicles.

Background: Medulloblastoma (MB) and diffuse infiltrative pontine glioma (DIPG) are malignant pediatric tumors. Extracellular vesicles (EVs) and their bioactive cargoes have been implicated in tumorigenesis. Most studies have focused on adult tumors, therefore the role of EVs and the noncoding RNA (ncRNA) landscape in pediatric brain tumors is not fully characterized.

Quantifying Ambulatory Care Use Preceding Emergency Department Visits and Hospitalizations for Ambulatory Care Sensitive Conditions.

Ambulatory Care Sensitive Conditions (ACSC) represent a significant source of health care spending in the United States. Existing literature is largely descriptive and there is limited information about how an emergency department (ED) visit or hospitalization for ACSCs is related to prior ambulatory care visits. A retrospective, observational study was conducted using health records from a large midwestern health system during a 20-month period between 2012 and 2014.

The prevalence, management, and thirty-day outcomes of symptomatic atrial fibrillation in a Tanzanian emergency department.

Introduction: Data describing atrial fibrillation (AF) care in emergency centres (ECs) in sub-Saharan Africa is lacking. We sought to describe the prevalence and outcomes of AF in a Tanzanian EC.

Methods: In a prospective, observational study, adults presenting with chest pain or shortness of breath to a Tanzanian EC were enrolled from January through October 2019.

Hospital Participation Decisions In Medicare Bundled Payment Program Were Influenced By Third-Party Conveners.

The Bundled Payments for Care Improvement initiative Advanced Model (BPCI Advanced) is a voluntary Medicare bundled payment model in which hospitals may participate with third-party conveners-private consulting firms that share in the financial risk built into the program. We found that nonteaching and for-profit status was associated with a higher probability of hospital partnership with third-party conveners in BPCI Advanced. Among hospitals participating in at least one inpatient clinical episode, hospitals that partnered with third-party conveners were more likely to select episodes with higher target prices: A $1,000 increase in episode target price was associated with a 1.

Heart failure care and outcomes in a Tanzanian emergency department: A prospective observational study.

Background: The burden of heart failure is growing in sub-Saharan Africa, but there is a dearth of data characterizing care and outcomes of heart failure patients in the region, particularly in emergency department settings.

Methods: In a prospective observational study, adult patients presenting with shortness of breath or chest pain to an emergency department in northern Tanzania were consecutively enrolled. Participants with a physician-documented clinical diagnosis of heart failure were included in the present analysis.

Administration of Purified Exosome Product in a Rat Sciatic Serve Reverse Autograft Model.

Background: The nerve autograft remains the gold standard when reconstructing peripheral nerve defects. However, although autograft repair can result in useful functional recovery, poor outcomes are common, and better treatments are needed. The purpose of this study was to evaluate the effect of purified exosome product on functional motor recovery and nerve-related gene expression in a rat sciatic nerve reverse autograft model.