Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Platelets, cell fragments traditionally thought of as important only for hemostasis, substantially and dynamically contribute to the immune system's response to infection. In addition, there is increasing evidence that externally active platelet entities, including platelet granules and platelet extracellular vesicles (PEVs), play a role not only in hemostasis, but also in inflammatory actions previously ascribed to platelets themselves. Given the functions of platelets and PEVs during inflammation and infection, their role in sepsis is being investigated. ⋯ Similar to cells traditionally ascribed to the immune system, including neutrophils, lymphocytes, and macrophages, platelets are instrumental in helping a host clear an infection, but are also implicated in the uncontrolled amplification of the immune response that leads to sepsis. Clearly, the function of platelets is more complicated than its simple structure and primary role in hemostasis initially suggest. This review provides an overview of platelet and platelet extracellular vesicle structure and function, highlighting the complex role platelets and PEVs play in the body in the context of infection and sepsis.
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The microRNA expression profile of plasma exosomes in osteosarcoma needs to be further explored. The present study intends to investigate the practicality of plasma exosomal miRNAs as novel biomarkers of osteosarcoma. In the study, exosome-like vesicles were purified from the plasma of patients with osteosarcoma and healthy control. ⋯ In comparison to the controls, the expression levels of miR-92a-3p, miR-130a-3p, miR-195-3 p, miR-335-5 p, let-7i-3p were upregulated in the exosomes from patients with osteosarcoma with statistical significance. Studies in vitro and in vivo have proved that osteosarcoma-secreted exosomes from miR-195-3 p upregulated 143B osteosarcoma cells promote cell proliferation and invasion. Overall, the present study identified exosomal miRNAs with dysregulated expression in patients with osteosarcoma, and they may have potential as targets for the treatment of patients with osteosarcoma.
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This study tests our hypothesis that patients with chronic obstructive pulmonary disease (COPD) have an increased risk of traumatic brain injury (TBI). In this nationwide retrospective cohort study, we used a subset of Taiwan's National Health Insurance Research Database, involving 1 million randomly selected beneficiaries. Patients with newly diagnosed COPD between 2000 and 2008 were identified. ⋯ The highest risk was observed in the 'COPDAE+' group that aged <65 (the adjusted HR was 1.92; 95% CI 1.39 to 2.64). COPD has been linked to complications beyond the respiratory system. In this study we showed that COPD is associated with an increased risk of TBI.
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ClC-5, the electrogenic chloride/proton exchanger strongly expressed in renal proximal tubules, belongs to the endocytic macromolecular complex responsible for albumin and low-molecular-weight protein uptake. ClC-5 was found to be overexpressed in glomeruli of glomerulonephritis and in cultured human podocytes under albumin overload. The transcriptional regulation of human ClC-5 is not fully understood. ⋯ The expression profile for all variants in normal and glomerulonephritis biopsies was similar, and variant 3 and alternative variant 4 were the most abundantly expressed in both sets. In glomerulonephritis biopsies, isoforms under the control of a weak promoter (variants 4, 6 and 7) showed an increased expression leading to an increase in the CLCN5 translated region, underscoring their importance in kidney pathophysiology. Since weak promoters can be turned on by different stimuli, these data support the hypothesis that proteinuria could be one of the stimuli capable of starting a signaling pathway that induces an increase in CLCN5 transcription.
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Clostridioides difficile is the most common cause of healthcare-associated infection and gastroenteritis-associated death in the USA. Adherence to guideline recommendations for treatment of severe C. difficile infection (CDI) is associated with improved clinical success and reduced mortality. The purpose of this study was to determine whether implementation of a pharmacist-led antimicrobial stewardship program (ASP) CDI initiative improved adherence to CDI treatment guidelines and clinical outcomes. ⋯ The proportion of patients on guideline adherent definitive CDI treatment regimen within 72 hours of diagnosis was significantly higher in the post-interventional group (pre: 42% vs post: 58%, p=0.02). No differences were observed in clinical outcomes or proportions of patients receiving laxatives, promotility agents, or proton pump inhibitors within 72 hours of diagnosis. Our findings demonstrate that a pharmacist-led stewardship initiative improved adherence to evidence-based practice guidelines for CDI treatment.