Publications by authors named "Stephen Miller"

Article Synopsis
  • Exposure to nitrogen mustard, a type of chemotherapy, causes skin damage and inflammation due to the recruitment of immune cells that worsen the injury and hinder healing.
  • Administering poly(lactic-co-glycolic acid) immune-modifying nanoparticles (PLGA-IMPs) right after exposure can reduce harmful immune cell accumulation in the skin and improve healing outcomes.
  • PLGA-IMPs promote the presence of regulatory T cells that help control inflammation by producing key anti-inflammatory cytokines, suggesting a potential treatment strategy for severe skin injuries.
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Volvox carteri is an excellent system for investigating the origins of cell differentiation because it possesses just two cell types, reproductive gonidia and motile somatic cells, which evolved relatively recently. The somatic phenotype depends on the regA gene, which represses cell growth and reproduction, preventing cells expressing it from growing large enough to become gonidia. regA encodes a putative transcription factor and was generated in an undifferentiated ancestor of V.

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The prospect of death is everywhere, but seldom directly addressed, in undergraduate medical education (UGME). Despite calls for UGME curricula to address the complex social and emotional aspects of death and dying, most curricula focus on biomedical, legal, and logistical aspects, or concentrate these topics within palliative care content and/or in simulations with simulated patients and manikins. We aimed to add to death education scholarship by exploring the complexities of death and dying within two dimensional simulations-i.

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(1) Background: Pulmonary hypertension (PH) increases pulmonary vascular resistance and right ventricular (RV) afterload. Assessment of RV systolic function in PH using RV fractional area change (RV FAC) as a marker directly correlates with mortality and the need for extracorporeal membrane oxygenation (ECMO). However, few studies have assessed neurodevelopmental outcomes.

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Background: Sepsis is a life-threatening emergency, and early recognition and treatment in the emergency department (ED) is critical to improving outcomes.

Methods: The authors implemented an interdisciplinary quality improvement (QI) project to standardize sepsis screening workflow across an academic health system consisting of a large tertiary care urban hospital, one freestanding ED, and two small rural affiliate hospitals (RA-1 and RA-2). The research team used the Institute for Healthcare Improvement Model for Improvement framework, consisting of iterative Plan-Do-Study-Act (PDSA) cycles.

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Article Synopsis
  • - Disulfide-constrained peptides (DCPs) are gaining popularity in drug development due to their stability and benefits of both large biologics and small molecules, but traditional chemical synthesis is costly and environmentally damaging.
  • - A new bioproduction platform was introduced for creating DCPs in a cost-effective and eco-friendly way, utilizing bacterial expression and innovative ligation techniques to produce modified versions of the model peptide MK1-3.6.10.
  • - The study also achieved high yields of specifically labeled MK1-3.6.10 and developed a semi-automated workflow for studying DCPs, showing promise for a sustainable approach to DCP discovery that reduces reliance on harmful chemicals and speeds up the process.
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In response to corneal injury, an activation of corneal epithelial stem cells and their direct progeny the early transit amplifying (eTA) cells to rapidly proliferate is critical for proper re-epithelialization. Thus, it is important to understand how such stem/eTA cell activation is regulated. Angiotensin-converting enzyme 2 (ACE2) is predominantly expressed in the stem/eTA-enriched limbal epithelium but its role in the limbal epithelium was unclear.

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Cumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models.

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Partial heart transplantation (PHT) is a novel surgical approach that involves transplantation of only the part of the heart containing a valve. The rationale for this approach is to deliver growing heart valve implants that reduce the need for future re-operations in children. However, prior to clinical application of this approach, it was important to assess it in a preclinical model.

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Partial heart transplantation is a new approach to deliver growing heart valve implants. Partial heart transplants differ from heart transplants because only the part of the heart containing the necessary heart valve is transplanted. This allows partial heart transplants to grow, similar to the valves in heart transplants.

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Article Synopsis
  • Food allergies are serious medical conditions driven by harmful immune responses to certain foods, with current treatments often being long and only temporarily effective.
  • Researchers are investigating the use of nanoparticles that encapsulate allergens to directly suppress the harmful immune cells (Th2 cells) responsible for allergic reactions.
  • In mouse studies, administering these nanoparticles showed promising results by significantly reducing severe allergic reactions and reprogramming the immune response to be less reactive to allergens.
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Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I) were recently identified in mature OLG and shown to play a role in regulating myelin length.

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Purpose: To determine whether there was a relationship between sleep position and symptomatic partial- and full-thickness rotator cuff tears.

Methods: A consecutive series of patients that met the inclusion/exclusion criteria (n = 58) were in seen in clinic between July 2019 and December 2019. All of these individuals had a significant partial-thickness (> 50%) or full-thickness rotator cuff tear determined by either ultrasound, magnetic resonance imaging, or both.

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Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process.

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Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation.

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Selective and precise activation of signaling transduction cascades is key for cellular reprogramming and tissue regeneration. However, the development of small- or large-molecule agonists for many signaling pathways has remained elusive and is rate limiting to realize the full clinical potential of regenerative medicine. Focusing on the Wnt pathway, here we describe a series of disulfide-constrained peptides (DCPs) that promote Wnt signaling activity by modulating the cell surface levels of ZNRF3, an E3 ubiquitin ligase that controls the abundance of the Wnt receptor complex FZD/LRP at the plasma membrane.

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Neuromyelitis optica spectrum disorder (NMOSD) is a CNS autoimmune inflammatory disease mediated by T helper 17 (Th17) and antibody responses to the water channel protein, aquaporin 4 (AQP4), and associated with astrocytopathy, demyelination and axonal loss. Knowledge about disease pathogenesis is limited and the search for new therapies impeded by the absence of a reliable animal model. In our work, we determined that NMOSD is characterized by decreased IFN-γ receptor signalling and that IFN-γ depletion in AQP4201-220-immunized C57BL/6 mice results in severe clinical disease resembling human NMOSD.

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Food allergy is a growing public health issue among children and adults that can lead to life-threatening anaphylaxis following allergen exposure. The criterion standard for disease management includes food avoidance and emergency epinephrine administration because current allergen-specific immunotherapy treatments are limited by adverse events and unsustained desensitization. A promising approach to remedy these shortcomings is the use of nanoparticle-based therapies that disrupt disease-driving immune mechanisms and induce more sustained tolerogenic immune pathways.

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Background: Hoof structure and health are essential for the welfare and productivity of beef cattle. Therefore, we assessed the genetic and genomic background of foot score traits in American (US) and Australian (AU) Angus cattle and investigated the feasibility of performing genomic evaluations combining data for foot score traits recorded in US and AU Angus cattle. The traits evaluated were foot angle (FA) and claw set (CS).

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In acute skin injury, healing is impaired by the excessive release of reactive oxygen species (ROS). Melanin, an efficient scavenger of radical species in the skin, performs a key role in ROS scavenging in response to UV radiation and is upregulated in response to toxic insult. In a chemical injury model in mice, we demonstrate that the topical application of synthetic melanin particles (SMPs) significantly decreases edema, reduces eschar detachment time, and increases the rate of wound area reduction compared to vehicle controls.

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