Painful vaso-occlusive episodes (VOEs) are the hallmark of sickle cell disease (SCD) and account for frequent visits to the emergency department (ED) or urgent care (UC). Currently, the early administration of analgesics is recommended as initial management; however, there is a need for further understanding of the effect of prompt analgesics and hydration during VOEs. The objective of this study is to analyze the factors associated with the rate of hospital admission in the setting of time to intravenous (IV) analgesics and hydration.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic has caused an international healthcare crisis and produced a large healthcare burden. Diabetes mellitus (DM) is a common disease that can be controlled via pharmacologic agents; however, many patients have poor glycemic control, leading to disease-related complications. DM has been reported in the literature to be associated with increasing morbidity and mortality in COVID-19 patients.
View Article and Find Full Text PDFBackground: Early reports have indicated a relationship between ABO and rhesus blood group types and infection with SARS-CoV-2. We aim to examine blood group type associations with COVID-19 mortality and disease severity.
Methods: This is a retrospective chart review of patients ages 18 years or older admitted to the hospital with COVID-19 between January 2020 and December 2021.
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome is the most common monogenic inherited cause of stroke.
Case Presentation: A female patient aged > 50 years with genetically proven CADASIL syndrome and an extensive stroke/transient ischemic attack (TIA) history experienced a bradycardic episode following hospitalization for new strokelike symptoms. The literature of cardiac involvement in CADASIL syndrome is limited, with no definitive recommendations for surveillance and screening.
Proton-pump inhibitors (PPIs) are commonly utilized in the treatment of upper gastrointestinal bleeds (UGIBs) due to their ability to stabilize blood clot formation. PPIs have been shown to reduce rebleeding after endoscopic hemostasis and reduce signs of bleeding at index endoscopy. While PPIs are well-tolerated and commonly administered to patients suffering from acute UGIBs, significant adverse effects may occur.
View Article and Find Full Text PDFIsocitrate dehydrogenase (IDH) mutations are common genetic alterations in myeloid disorders, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Epigenetic changes, including abnormal histone and DNA methylation, have been implicated in the pathogenic build-up of hematopoietic progenitors, but it is still unclear whether and how IDH mutations themselves affect hematopoiesis. Here, we show that IDH1-mutant mice develop myeloid dysplasia in that these animals exhibit anemia, ineffective erythropoiesis, and increased immature progenitors and erythroblasts.
View Article and Find Full Text PDFAdherent neutrophils on vascular endothelium positively contribute to cell-cell aggregation and vaso-occlusion in sickle cell disease. In the present study, we demonstrated that pyridoxamine, a derivative of vitamin B6, might be a therapeutic agent to alleviate intravascular cell-cell aggregation in sickle cell disease. Using real-time intravital microscopy, we found that one oral administration of pyridoxamine dose-dependently increased the rolling influx of neutrophils and reduced neutrophil adhesion to endothelial cells in cremaster microvessels of sickle cell disease mice challenged with hypoxia-reoxygenation.
View Article and Find Full Text PDFInteractions of neutrophils with endothelial cells (ECs) and platelets contribute to tissue damage and vascular occlusion under sterile inflammatory conditions. However, the molecular mechanisms regulating the cell-cell interactions remain poorly understood. Previous studies suggest that reactive oxygen species, such as hydrogen peroxide (HO), produced from NADPH oxidase 2 play a critical role in platelet-neutrophil interactions by regulating the function of neutrophil αMβ2 integrin during sterile inflammation.
View Article and Find Full Text PDFDownstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, is known to modulate pain responses. However, it is unknown whether DREAM is expressed in anucleate platelets and plays a role in thrombogenesis. By using intravital microscopy with DREAM-null mice and their bone marrow chimeras, we demonstrated that both hematopoietic and nonhematopoietic cell DREAMs are required for platelet thrombus formation following laser-induced arteriolar injury.
View Article and Find Full Text PDFMutations in the isocitrate dehydrogenase-1 gene (IDH1) are common drivers of acute myeloid leukemia (AML) but their mechanism is not fully understood. It is thought that IDH1 mutants act by inhibiting TET2 to alter DNA methylation, but there are significant unexplained clinical differences between IDH1- and TET2-mutant diseases. We have discovered that mice expressing endogenous mutant IDH1 have reduced numbers of hematopoietic stem cells (HSCs), in contrast to Tet2 knockout (TET2-KO) mice.
View Article and Find Full Text PDFEvid Based Complement Alternat Med
April 2016
Purpose. A patient-assessor-blinded, randomized, sham-controlled crossover trial was performed to investigate the effectiveness of laser acupuncture on anthropometric measurements and appetite sensation in obese subjects. Methods.
View Article and Find Full Text PDFBackground: Insulinomas are the most common type of neuroendocrine (NE) pancreatic islet tumors. Patients with insulinomas may develop complications associated with hyperinsulinemia. To increase the treatment options for insulinoma patients, we have tested a conditionally replicating adenovirus that has been engineered in such a way that it can specifically express therapeutic genes in NE tumors.
View Article and Find Full Text PDFAccurate detection of neuroendocrine (NE) tumors is critically important for better prognosis and treatment outcomes in patients. To demonstrate the efficacy of using an adenoviral vector for the detection of NE tumors, we have constructed a pair of adenoviral vectors which, in combination, can conditionally replicate and release Gaussia luciferase into the circulation after infecting the NE tumors. The expression of these two vectors is regulated upstream by an INSM1-promoter (insulinoma-associated-1) that is specifically active in NE tumors and developing NE tissues, but silenced in normal adult tissues.
View Article and Find Full Text PDFAdvancement of engineered ear in clinical practice is limited by several challenges. The complex, largely unsupported, three-dimensional auricular neocartilage structure is difficult to maintain. Neocartilage formation is challenging in an immunocompetent host due to active inflammatory and immunological responses.
View Article and Find Full Text PDFPlatelet-leukocyte interactions on activated endothelial cells play an important role during microvascular occlusion under oxidative stress conditions. However, it remains poorly understood how neutrophil-platelet interactions are regulated during vascular inflammation. By using intravital microscopy with mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their bone marrow chimera, we demonstrated that NOX2 from both hematopoietic and endothelial cells is crucial for neutrophil-platelet interactions during tumor necrosis factor alpha-induced venular inflammation.
View Article and Find Full Text PDFObjective: Our goal was to engineer cartilage in vivo using auricular chondrocytes that underwent clinically relevant expansion and using methodologies that could be easily translated into health care practice.
Design: Sheep and human chondrocytes were isolated from auricular cartilage biopsies and expanded in vitro. To reverse dedifferentiation, expanded cells were either mixed with cryopreserved P0 chondrocytes at the time of seeding onto porous collagen scaffolds or proliferated with basic fibroblast growth factor (bFGF).
Background: Obesity-related diseases have a profound economic impact on health care systems. Laser acupuncture has been shown to have beneficial effects on obesity. However, to our knowledge, those trials were either non-randomized, non-blinded or included low-calorie diet control.
View Article and Find Full Text PDFThe Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D.
View Article and Find Full Text PDFPlatelets primarily mediate hemostasis and thrombosis, whereas leukocytes are responsible for immune responses. Since platelets interact with leukocytes at the site of vascular injury, thrombosis and vascular inflammation are closely intertwined and occur consecutively. Recent studies using real-time imaging technology demonstrated that platelet-neutrophil interactions on the activated endothelium are an important determinant of microvascular occlusion during thromboinflammatory disease in which inflammation is coupled to thrombosis.
View Article and Find Full Text PDFBackground: Carved autologous costal cartilage and porous polyethylene implants (Medpor) are the most common approaches for total ear reconstruction, but these approaches may have inconsistent cosmetic outcomes, a high risk of extrusion, or other surgical complications. Engineering ear cartilage to emulate native auricular tissue is an appealing approach, but often the cell-seeded scaffolds are susceptible to shrinkage and architectural changes when placed in vivo. The aim of this study was to assess the most favorable conditions for in vitro pre-culture of cell-seeded type I collagen scaffolds prior to in vivo implantation.
View Article and Find Full Text PDFMesenchymal stem cells (MSCs), as well as osteoblastic cells derived from these MSCs, have been shown to be key components of the hematopoietic stem cell (HSC) niche. In this study, we wished to examine whether other cell types that are known to differentiate from MSCs similarly regulate the stem cell niche, namely cells of the adipocyte lineage. Recent studies have examined the role that adipocytes play in the biology of the HSCs in different bone locations and in transplantation settings; however, none have examined their role under homeostatic conditions.
View Article and Find Full Text PDFTissue-engineered cartilage has historically been an attractive alternative treatment option for auricular reconstruction. However, the ability to reliably generate autologous auricular neocartilage in an immunocompetent preclinical model should first be established. The objectives of this study were to demonstrate engineered autologous auricular cartilage in the immunologically aggressive subcutaneous environment of an immunocompetent animal model, and to determine the impact of in vitro culture duration of chondrocyte-seeded constructs on the quality of neocartilage maturation in vivo.
View Article and Find Full Text PDFFinite element analysis (FEA), CT based structural rigidity analysis (CTRA) and mechanical testing is performed to assess the compressive failure load of rat tibia with simulated lytic defects. Twenty rat tibia were randomly assigned to four equal groups (n=5). Three of the groups included a simulated defect at various locations: anterior bone surface (Group 1), posterior bone surface (Group 2) and through bone defect (Group 3).
View Article and Find Full Text PDF