Merkel Cell Carcinoma is a rare and aggressive cutaneous carcinoma with a propensity for metastasis and death. Our study describes the prevalence, sociodemographics and inpatient mortality of Merkel Cell Carcinoma related hospitalizations in the United States from 2011 to 2020. We conducted an observational study using the Nationwide Inpatient Sample database, which captures a 20% sample of all hospitalizations in the United States.
View Article and Find Full Text PDFThe survival rate of pediatric acute myeloid leukemia (pAML) is currently around 60%. While survival has slowly increased over the past few decades, the development of novel agents likely to further improve survival for this heterogeneous patient population has been limited by gaps in the pAML pre-clinical pipeline. One of the major hurdles in evaluating new agents for pAML is the lack of pAML patient-derived xenograft (PDX) models.
View Article and Find Full Text PDFTryptophan modulates disease activity and the composition of microbiota in the B6. (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet.
View Article and Find Full Text PDFBackground: There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood.
Methods: For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014).
Background: Most theorists and medical educators agree that a curriculum rich in active learning (AL) strategies, such as a flipped classroom, is superior to passive listening to promote better retention and application of new knowledge. Although AL multimodal teaching strategies have been considered the most effective, including online virtual teaching, voice-over pre-recorded lectures, and, more recently, the addition of artificial intelligence (AI), data on the effectiveness of these methods in medical education is scarce. The present educational research study examined the effectiveness of voice-over-style lectures and AI in facilitating learning outcomes as assessed by test scores after participating in basic science lectures in a medical school setting.
View Article and Find Full Text PDFBackground: Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes.
Objectives: In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry.
Methods: HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB or through breastfeeding, if applicable (F1).
Background: Polybrominated biphenyls (PBBs), a class of endocrine disrupting chemicals, were the main chemicals present in one of the largest industrial accidents in the United States. We investigated the association between serum PBB-153 levels and autoimmune disorders among members of the Michigan PBB Registry.
Methods: Eight hundred and ninety-five members of the registry had both a serum PBB-153 measurement and had completed one or more questionnaires about autoimmune disorders.
Background: Mounting evidence suggests that increased gut permeability, or leaky gut, and the resulting translocation of pathobionts or their metabolites contributes to the pathogenesis of Systemic Lupus Erythematosus. However, the mechanisms underlying the induction of gut leakage remain unclear. In this study, we examined the effect of a treatment with a TLR7/8 agonist in the B6.
View Article and Find Full Text PDFSurvival of pediatric AML remains poor despite maximized myelosuppressive therapy. The (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients.
View Article and Find Full Text PDFThe activation of lymphocytes in patients with lupus and in mouse models of the disease is coupled with an increased cellular metabolism in which glucose plays a major role. The pharmacological inhibition of glycolysis with 2-deoxy-d-glucose (2DG) reversed the expansion of follicular helper CD4+ T cells and germinal center B cells in lupus-prone mice, as well as the production of autoantibodies. The response of foreign Ags was however not affected by 2DG in these mice, suggesting that B and CD4+ T cell activation by autoantigens is uniquely sensitive to glycolysis.
View Article and Find Full Text PDFBackground: An industrial accident led to the widespread contamination of polybrominated biphenyl (PBB), a flame retardant, into the food system in Michigan in the 1970's. PBB continues to be detected in Michiganders' blood some forty years later. It is necessary to understand the elimination rate and half-life of PBB because it may provide clues on how to hasten the elimination of it from the human body.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform.
View Article and Find Full Text PDFTo measure the association between intravenous administration of monoclonal antibody bamlanivimab (LY-CoV555) to long-term care facility (LTCF) residents recently diagnosed with pre-symptomatic, mild-to-moderate COVID-19 and are considered high risk for disease progression with mortality, hospitalization, and adverse effects. A retrospective analysis of LTCF residents with confirmed COVID-19, pre-symptomatic, mild to moderate disease, who were treated with bamlanivimab (LY-CoV555) were compared to similar LTCF residents who did not receive monoclonal antibody treatment. Dependent variables investigated included mortality and hospitalization as primary outcomes with adverse effects as the secondary outcome.
View Article and Find Full Text PDFWe report a novel model of lupus-associated cardiovascular pathology accelerated by the TLR7 agonist R848 in lupus-prone B6. (TC) mice. R848-treated TC mice but not non-autoimmune C57BL/6 (B6) controls developed microvascular inflammation and myocytolysis with intracellular vacuolization.
View Article and Find Full Text PDFA high prevalence of metabolic syndrome (MetS) has been reported in multiple cohorts of systemic lupus erythematosus (SLE) patients, most likely as one of the consequences of autoimmune pathogenesis. Although MetS has been associated with inflammation, its consequences on the lupus immune system and on disease manifestations are largely unknown. The metabolism of immune cells is altered and overactivated in mouse models as well as in patients with SLE, and several metabolic inhibitors have shown therapeutic benefits.
View Article and Find Full Text PDFBackground According to the decennial Osteopathic Survey of Healthcare in America, the osteopathic profession has been steadily gaining recognition in the United States, particularly among the White/Caucasian demographic. This, however, does not take into account immigrant European communities that, while racially classified as White/Caucasian, may be unexposed to osteopathic physicians (DOs) in their home country and may be reticent to osteopathic manipulative medicine. Data on non-English-speaking communities are limited and can mask the need for further outreach.
View Article and Find Full Text PDFSomatic mutations are rare in pediatric acute myeloid leukemia (pAML), indicating that alternate strategies are needed to identify targetable dependencies. We performed the first enhancer mapping of pAML in 22 patient samples. Generally, pAML samples were distinct from adult AML samples, and MLL (KMT2A)-rearranged samples were also distinct from non-KMT2A-rearranged samples.
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