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HMS Theses and Dissertations

Mostrando recursos 1 - 20 de 53

  1. Understanding the Impact of Acute Stressor During Simulation on Medical Students' Short and Long-Term Clinical Skills Retention

    Hasdianda, Mohammad Adrian
    Background: Acute stressors may be beneficial when embedded in simulation scenario to promote better skills retention. We aimed to establish the impact of acute stressors to medical students’ short-and long-term retention of intravenous catheterization skills. Methods: Forty-five participants took part in the intravenous catheterization simulation using standardized patients in treatment (Stress) and control (Non-Stress) groups. Participants were asked to complete State-Trait Anxiety Inventory and assessed on their skills performance before, shortly after and twenty days after the simulation session. We continuously recorded participants’ heart rate during the simulation. Results: No significant difference and interaction were found between pre-simulation, short-term, and long-term skills performance scores for...

  2. Let’s Talk Again, Now That We Have Our “Sea Legs”: A Qualitative Needs Assessment for a Novel Structured Conversation Targeting the Early Cancer Treatment Period

    Feraco, Angela
    Background: The initial months of childhood cancer treatment may occasion changed illness understanding and altered communication needs among families compared with those at diagnosis, but currently, there is no framework to guide communication in this early cancer treatment period (ECTP). Objectives: To elicit (1) lived illness experiences during ECTP, (2) conceptual acceptability of a novel in-depth conversation between families and their pediatric oncologists, the “Day 100 Talk,” (D100) during this period, (3) preferred topics and goals for D100, and (4) potential barriers to D100. Design/Method: We conducted semi-structured interviews with children aged ≥13 years and parents of all-aged children with non-relapsed...

  3. Strategies for Building Effective International Educational Collaborations

    Alfadhel, Mansour A.
    In a country like Saudi Arabia, neither the resources nor the infrastructure for higher health education programs are available locally, and at the same time healthcare organizations are expanding dramatically. To overcome these deficiencies, institutions tend to establish several international collaborations in various healthcare specialties as needed. Supporting and encouraging the improvement of these collaborations in this part of the world is crucial. Understanding the processes that assist in building and sustaining effective collaborations will continue to be an important step in program design, implementation, and evaluation of these international collaborations. This study aims to explore the key factors that...

  4. Flipped Classroom in a Collectivistic Society: Reactions & Suggestions

    Pathanasethpong, Atipong
    Flipped classroom is an educational format that has been proven to provide many benefits. However, the format requires outspokenness and thus may not be congruent with collectivistic cultures. The present study was conducted to gain better understanding of flipped classroom in Thailand, a collectivistic country. Qualitative portion of the study employed interpretative phenomenological analysis, while the quantitative portion was conducted in quasi-experimental approach. Fifth-year medical students and faculty members were recruited to learn and teach using a flipped classroom model in a period covering three clinical rotations, with 13 to 15 students in each. Students were required to prepare themselves with...

  5. Longitudinal Integrated Training in Residency: A Paradigm Shift Towards Structural Solutions for Achieving Key Educational Competencies

    Michelson, Catherine D.
    Graduate medical education typically organizes clinical training into discrete rotations. Longitudinal integrated clerkships, recently adopted by undergraduate medical educators, have been shown to achieve important educational outcomes for students including greater patient-centeredness, advocacy, and integration with teams. Despite the introduction of longitudinal, integrated clerkships into undergraduate medical education, this training structure has rarely been used in graduate medical education. This study explored residents’ experiences and reflections on a longitudinal integrated block implemented in a large pediatric residency program. Residents were purposively sampled to participate in an interview or focus group discussion after completing the longitudinal integrated block. Using a phenomenologic framework,...

  6. Stress From Uncertainty and Resilience Among Depressed and Burnt Out Residents: Cross-Sectional Study

    Simpkin, Arabella L.
    Objective: To determine how stress from uncertainty is related to resilience among pediatric residents and whether these attributes are associated with depression and burnout. Study Design and Setting: Cross-sectional study of 50 residents in pediatric residency programs from four urban freestanding children’s hospitals in the United States and Canada. Main outcome measures: Stress from uncertainty using the Physicians’ Reaction to Uncertainty Scale, resilience using the 14-item Resilience Scale, depression using the Harvard national depression screening scale, and burnout using single item measures of emotional exhaustion and depersonalization from the Maslach Burnout Inventory. Results: There was a strong correlation between stress from uncertainty and...

  7. Treg-Rich Organized Lymphoid Structures That Develop In Spontaneously Accepted Murine Renal Allografts Have Thymic-Like Characteristics

    Ashry, Tameem
    Introduction: Novel lymphoid structures identified within the parenchyma of kidney allografts are associated with the induction of spontaneous or active immune tolerance. They appear to be distinct from classic tertiary lymphoid structures and are rich in regulatory T cells (Tregs) thus, have been named Treg-rich Organized Lymphoid Structures or TOLs. It is possible that TOLs promote tolerance by regulatory of deletional mechanisms as in a thymus. Here, we determine whether TOLs have thymic-like characteristics by phenotyping the antigens expressed within TOLs. Many markers such as Aire or Foxn1 were previously thought to be unique to the thymus. However, they have...

  8. PRO136ALA CTLA4 Mutation

    Palmer, Cody
    Cytotoxic T lymphocyte antigen–4 (CTLA-4) is an inhibitory receptor involved in the regulation of immune responses. Deficiency of Ctla4 in mice causes fatal multiorgan lymphocytic infiltration. We identified a heterozygous, missense c.406C>G, p.P136A mutation in CTLA4 in a CVID patient. This mutation is within the binding motif of CTLA-4 and is predicted to interfere with ligand binding. To test whether this mutation is causal in the phenotype of the patient, we will use CRISPR/Cas9-mediated genome editing to clone the mutation into a regulatory T cell-like cell line and use the edited cell line for functional studies.

  9. Defining Immune Cell Profiles and their Role in Predicting Therapeutic Response in Multiple Myeloma

    Acharya, Shree
    Multiple myeloma (MM) is a plasma cell malignancy that presents with bone marrow plasmacytosis, monoclonal paraproteinemia, and associated end organ damage, including anemia, renal dysfunction and bone disease, amongst others (23, 38, 39). The growth and survival of myeloma cells is driven by inherent genomic perturbations as well as influence of the bone marrow microenvironment (17). Numerous constituents of the bone marrow (BM) microenvironment, including immune cells, are affected both directly and indirectly by MM cells, leading to immune cell dysfunction. The most prominent immune deficiency lies in the humoral immune response, which manifests as low uninvolved immunoglobulin (UIg) levels...

  10. Phosphatases in Mouse Mast Cell Rapid IgE Desensitization: The Role of SHIP-1

    AlEnazy, Leila Askar
    Rapid Drug Desensitization (RDD) is a widely used and effective clinical approach to enable allergic individuals to temporary tolerate various drugs to which they have an IgE-mediated hypersensitivity reaction. Latest studies have found mast cells (MCs) as the primary target cells for Desensitization (DS). Studies on both in vitro and in vivo murine rapid IgE/MCs DS showed impairment of all MC activation hallmarks such as receptor internalization, calcium mobilization, degranulation, production of lipid mediators and cytokines. However, the molecular targets and underlying mechanisms behind this process remain unclear. Previous studies have shown that the inositol phosphatase SHIP acts as a...

  11. Immune Modulation by Exosomes in Trichomonas Vaginalis Infection

    Chan, Tiffany
    Exosomes and their microRNA cargo have been shown to modulate immune gene expression in the context of cancer; however, they are still a largely uncharted territory in the context of reproductive tract immunology. We used a human in-vitro model of the most common non-viral infection of the lower female reproductive tract caused by the protozoan parasite Trichomonas vaginalis (TV) to begin unveiling the role of exosomes in the host-microbe interactions in this anatomic compartment. We isolated exosomes from monocultures of different TV strains and from vaginal epithelial-TV co-cultures and investigated their effects on the acute immune response by bystander upper...

  12. CX3CR1: Re-Defining Exhausted CD8+ T Cell Populations

    ElJalby, Mahmoud
    Persistent infections result in dysfunctional state of CD8+ T cells associated with the expression of multiple inhibitory receptors. Recent studies have attempted to elucidate T cell subsets in chronic infections1–5. Similarly, the chemokine receptor CX3CR1 has been recently three effector and memory subsets6. Here, we show that CX3CR1 potentially identifies three subsets of exhausted CD8+ T cells in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). Preliminary data indicate a notable delay in the formation of the CX3CR1hi subset at the effector stage. The CX3CR1hi cells were localized to the blood while the CX3CR1- and CX3CR1int cells resided in the...

  13. A Focused Approach to the Diagnosis of Primary Immunodeficiencies

    Alsaati, Nouf
    Primary immunodeficiencies (PIDs) are genetic disorders impairing host immunity, leading to life-threatening infections, autoimmunity, and/or malignancies. Early diagnosis is the mainstay of treatment for PIDs. Delays in diagnosis can result in increased morbidity and mortality. Genomic technologies have been critical for expediting the discovery of novel genetic defects underlying PIDs, expanding our knowledge of the complex clinical phenotypes associated with PIDs, and in shifting paradigms of PID pathogenesis. Once considered Mendelian, monogenic, and completely penetrant disorders, genomic studies have redefined PIDs as a heterogeneous group of diseases found in the global population that may arise through multigenic defects, non-germline transmission,...

  14. The Role of Tissue-Resident Macrophages in Transplant Immunity

    Ualiyeva, Saltanat
    Successful engraftment of Vascular Composite Allotransplantation (VCA), including face transplants, provides functional and quality of life benefits to the recipient. There is significant interest in developing predictive biomarkers that will identify rejection episodes at the earliest possible moment thereby enabling clinicians to preemptively treat rejection episodes, safely guide maintenance immunosuppression minimization or withdrawal, and improve rejection surveillance for investigational therapies. Tissue-resident macrophages (TRMs) are a population of sentinel phagocytes that are present in virtually all tissues, particularly at barrier sites such as skin that are substantial components of VCA, and arise from yolk-sac not bone marrow derived precursors. We are...

  15. Characterization of Human Liver Stromal Cells

    Guinn, Samantha
    The liver is a highly immunologic, metabolic organ in the body with many functions including but not limited to amino acid and carbohydrate metabolism, synthesis of plasma proteins, metabolism of pharmaceuticals, defense against pathogens, and more. There are two types of stromal cells in the liver: liver sinusoidal endothelial cells and hepatic stellate cells. The goal of this thesis is to determine markers that can be used to identify human stromal cells. I investigated the expression of cellular surface and intracellular molecules on human stromal cells isolated from human livers. The cellular markers for this work in human samples were...

  16. Profiling Cytokine Expression in Trauma Patients Before and After TLR Stimulation

    Levers, Najah A.
    Trauma is the leading cause of morbidity and mortality worldwide for individuals under the age of 45. Despite advances in emergency care, infection continues to be a major complication contributing to significantly high death rates. This is prevalent because traumatic injuries induce a complex host response mediated by pattern recognition receptors that disrupt immune homeostasis and predispose trauma patients to opportunistic infections. Recent studies have demonstrated the immunotherapeutic benefits of using a TLR9 agonist, CpG-ODN in mouse models of trauma. Therefore, it is imperative to continue to investigate the biological effects of CpG-ODN as well as other TLR agonists in...

  17. Antigens in the Pathogenesis of Immunoglobulin G4 - Related Disease

    Alsalem, Sultan Bandar
    Immunoglobulin G4-Related Disease (IgG4-RD) is a chronic, fibroinflammatory disorder capable of affecting every organ system. Under the umbrella of IgG4-RD, many poorly characterized eponymous disorders such as Kuttner’s tumor, Mikulicz disease, and Ormond’s disease have been unified based on shared serologic and histopathological features. The pathogenesis of IgG4-RD is thought to involve plasmablasts (circulating antibody secreting cells), CD4+ cytotoxic T cells (CD4+ CTLs) and IL-4 secreting follicular helper T cells. What antigen or collection of antigens these cells are responding to remains unknown. Similarly, whether such antigens are of a self or an exogenous source has not been clarified. In...

  18. MHC Class II-Peptide Complexes Displayed on Activated T Cells Guide Treg Suppression

    Fryer, Madeline Louise
    Background: Regulatory T cell (Treg) therapy remains a promising strategy for minimizing immunosuppression and extending allograft survival. Treg suppression requires initial activation through Treg-target cell contacts and T cell receptor (TCR) engagement, however, the precise nature of these interactions in the context of allogeneic settings remains to be elucidated. Studies indicate that inflammation facilitates transfer of peptide-MHC-II complexes(pMHCII) from antigen presenting cells (APCs) to activated T cells. Thus, we hypothesize that during inflammation associated with organ transplantation, pMHC-II complexes relocate to alloreactive T effector cells and serve as Treg activation signals. Methods: Transfers of pMHC-II complexes onto activated T effector cell...

  19. Developing a Novel Platform for Neoantigen Identification

    Srivangipuram, Sriya
    Tumor infiltrating CD8+ cytotoxic T lymphocytes (CTLs) recognize tumor-derived peptide antigens, or neoantigens, presented on MHC Class I molecules to elicit an anti-tumor immune response. Neoantigens originate from the accumulation of tumor-specific somatic mutations in DNA sequences, such as point and frameshift mutations. These mutations generate modified peptides that can be found uniquely on the surface of a tumor cell, making them crucial target molecules in cancer immunotherapies for limiting off-target toxicity effects. The ability to identify neoantigens remains a great challenge in the field. This thesis is focused on the development of a platform for neoantigen discovery and isolation...

  20. A Distinct Esophageal mRNA Pattern Stamp Identifies a Subpopulation of EoE Patients With Food Impactions

    Acar, Utkucan
    Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disorder of esophagus characterized by eosinophil-rich infiltrates. A significant portion of EoE patients suffer from esophageal food impactions. The underlying mechanism of food impactions is not well understood. Food impactions can happen in the absence of an anatomical problem in the esophagus. Previous literature shows evidence for abnormal esophageal motility in EoE patients. This implies that impaired motility of the esophagus is likely the cause of food impactions in EoE patients. Motility in the gastrointestinal tract is under the control of the nervous system. Nitric oxide (NO) is the main inhibitory neurotransmitter...

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