• Byskov Gordon opublikował 1 rok, 3 miesiące temu

    The cartilage collagen network and chondrocytes from the 3D contrast-enhanced XRM were correlated with the 2D histology. This technique has two distinct advantages over routine histopathology (1) the avoidance of dehydration, demineralization, and deformation of histological sectioning, thereby preserving the intact articular cartilage and subchondral bone plate ex vivo, and (2) the ability to evaluate the entire osteochondral volume in 3D. This work explores several diagnostic features of imaging cartilage, including visualization of the tidemark in XRM and SHG-DP microscopy, validating the morphology of chondrocytes and nuclei with XRM, SHG-DP and PLM, and correlating collagen birefringence with XRM image intensity.

    The novel coronavirus (CoV) disease 2019 (COVID-19) is a viral infection that causes severe acute respiratory syndrome (SARS). It is believed that early reports of COVID-19 cases were noticed in December 2019 and soon after it became a global public health emergency. It is advised that COVID-19 transmits through human to human contact and in most cases, it remains asymptomatic. Several approaches are being utilized to control the outbreak of this fatal viral disease. microRNAs (miRNAs) are known signature therapeutic tool for the viral diseases; they are small non-coding RNAs that target the mRNAs to inhibit their post-transcriptional expression, therefore, impeding their functions, can serve as watchdogs or micromanagers in the cells.

    This review work delineated COVID-19 and its association with SARS and Middle East respiratory syndrome (MERS), the possible role of miRNAs in the pathogenesis of COVID-19, and therapeutic potential of miRNAs and their effective delivery to treat COVID-19.

    This review highlighted the importance of various miRNAs and their potential role in fighting with this pandemic as therapeutic molecules utilizing nanotechnology.

    This review highlighted the importance of various miRNAs and their potential role in fighting with this pandemic as therapeutic molecules utilizing nanotechnology.In this article, we describe a science- and justice-based framework for promoting health equity designed for researchers and practitioners working across public health and social science fields. We developed the health equity framework (HEF; etr.org/healthequityframework) in two phases of iterative development. Building on existing models, the HEF illustrates how health outcomes are influenced by complex interactions between people and their environments. The framework centers on three foundational concepts equity at the core of health outcomes; multiple, interacting spheres of influence; and a historical and life-course perspective. Health equity is defined as having the personal agency and fair access to resources and opportunities needed to achieve the best possible physical, emotional, and social well-being. By centering population outcomes, the HEF encourages researchers and practitioners to think beyond traditional approaches that focus on individual behaviors and choices to assess and identify their gaps in acknowledging and addressing factors from multiple spheres of influence. We identified four, interacting spheres of influence that represent both categories of risk and protective factors for health outcomes as well as opportunities for strategies and interventions that address those factors. The HEF highlights the explicit and implicit interactions of multilevel influences on health outcomes and emphasizes that health inequities are the result of cumulative experiences across the life span and generations. The HEF is a practical tool for leaders and professionals in public health research and practice to reflect on and support a shift toward addressing health inequities resulting from the interplay of structural, relational, individual, and physiological factors.Association between selection pressure caused by the use of azole fungicides in sawmills and the development of fungal resistance has been described. The aim of this study was to implement an algorithm to assess the presence of Aspergillus section Fumigati resistant strains in sawmills. Eighty-six full-shift inhalable dust samples were collected from eleven industrial sawmills in Norway. Different culture media were used and molecular identification to species level in Aspergillus section Fumigati was done by calmodulin sequencing and TR34/L98H and TR46/Y121F/T289A mutations were screened by real-time PCR assay and confirmed by cyp51A sequencing. Six Fumigati isolates were identified as A. fumigatus sensu stricto and two of these grew on azole-supplemented media and were further analyzed by real-time PCR. One was confirmed to be a TR34/L98H mutant. The obtained results reinforce the need to assess the presence of A. fumigatus sensu stricto resistant isolates at other workplaces with fungicide pressure.Objectives Management of radiation-induced ureteral stricture (RIUS) is complex, requiring chronic drainage or morbid definitive open reconstruction. Herein, we report our multi-institutional comprehensive experience with robotic ureteral reconstruction (RUR) in patients with RIUSs. Patients and Methods In a retrospective review of our multi-institutional RUR database between January 2013 and January 2020, we identified patients with RIUSs. Five major reconstruction techniques were utilized end-to-end (anastomosing the bladder to the transected ureter) and side-to-side (anastomosing the bladder to an anterior ureterotomy proximal to the stricture without ureteral transection) ureteral reimplantation, buccal or appendiceal mucosa graft ureteroplasty, appendiceal bypass graft, and ileal ureter interposition. When necessary, adjunctive procedures were performed for mobility (i.e., psoas hitch) and improved vascularity (i.e., omental wrap). Outcomes of surgery were determined by the absence of flank pain (clinicaerform adjunctive procedures for mobility and improved vascularity due to poor tissue quality. Repeat procedures for RIUSs heighten the risk of necrosis and failure.Purpose To evaluate the efficacy and safety of benign prostatic obstruction (BPO) surgery in patients with preoperative urinary catheterization. Patients and Methods We conducted a multi-institutional retrospective study including all patients who failed a trial without catheter (TWOC) after acute urinary retention (AUR) between January 2017 and January 2019. Patients with neurogenic bladder, prostate cancer, or urethral stricture were excluded from the analysis. Patients underwent either monopolar/bipolar transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), prostate artery embolization (PAE), open prostatectomy (OP), or endoscopic enucleation. The primary endpoint was 12-month urinary catheter-free survival without using benign prostatic hyperplasia medications. Results One hundred seventy-one consecutive men (median age 71 years; median prostate volume 75 cm3) underwent BPO surgery, including 48 (28%) TURP, 62 (36.3%) PVP, 21 (12.3%) endoscopic enucleation, 15 (8.8%) PAE, and 25 (14.6%) OP. The median duration of preoperative urinary catheterization was 69 days (interquartile range 46-125). The 12-month urinary catheter-free survival rate was 84.8% (145/171). Satisfactory voiding returned to 121 patients (70.8%). On backward stepwise multivariable analysis, PVP (odds ratio [OR] 0.27 [0.10-0.69]; p = 0.008), PAE (OR 5.27 [1.28-27.75]; p = 0.03), endoscopic enucleation (OR 0.08 [0-0.49]; p = 0.023), OP (OR 0.10 [0.01-0.57]; p = 0.034), Charlson score (OR 1.36 [1.14-1.66]; p = 0.001), and number of preoperative TWOC failure (OR 2.53 [1.23-5.51]; p = 0.014) were significantly associated with catheter-free survival. Conclusions In this multi-institutional retrospective study, including patients with preoperative catheterization, the overall success rate of BPO surgery was 70.8% after 1-year follow-up. Compared with TURP, enucleation methods and PVP were associated with better catheter-free survival, whereas PAE was associated with higher risk of AUR recurrence.

    We sought to identify and investigate the functional role of the major endothelial cell (EC)-derived factors that control pericyte recruitment to EC tubes and pericyte-induced tube maturation during capillary network formation. Approach and Results We identify PDGF (platelet-derived growth factor)-BB, PDGF-DD, ET (endothelin)-1, TGF (transforming growth factor)-β, and HB-EGF (heparin-binding epidermal growth factor), as the key individual and combined regulators of pericyte assembly around EC tubes. Using novel pericyte only assays, we demonstrate that PDGF-BB, PDGF-DD, and ET-1 are the primary direct drivers of pericyte invasion. Their addition to pericytes induces invasion as if ECs were present. In contrast, TGF-β and HB-EGF have minimal ability to directly stimulate pericyte invasion. In contrast, TGF-β1 can act as an upstream pericyte primer to stimulate invasion in response to PDGFs and ET-1. HB-EGF stimulates pericyte proliferation along with PDGFs and ET-1. Using EC-pericyte cocultures, individual, pericyte-induced basement membrane deposition during capillary network assembly.

    The risk of thrombosis in myeloproliferative neoplasms, such as primary myelofibrosis varies depending on the type of key driving mutation (JAK2 [janus kinase 2], CALR [calreticulin], and MPL [myeloproliferative leukemia protein or thrombopoietin receptor]) and the accompanying mutations in other genes. In the current study, we sought to examine the propensity for thrombosis, as well as platelet activation properties in a mouse model of primary myelofibrosis induced by JAK2

    (janus kinase 2 with valine to phenylalanine substitution on codon 617) mutation. Approach and Results Vav1-hJAK2

    transgenic mice show hallmarks of primary myelofibrosis, including significant megakaryocytosis and bone marrow fibrosis, with a moderate increase in red blood cells and platelet number. This mouse model was used to study responses to 2 models of vascular injury and to investigate platelet properties. Platelets derived from the mutated mice have reduced aggregation in response to collagen, reduced thrombus formation and thrombus size, as demonstrated using laser-induced or FeCl

    -induced vascular injury models, and increased bleeding time. Strikingly, the mutated platelets had a significantly reduced number of dense granules, which could explain impaired ADP secretion upon platelet activation, and a diminished second wave of activation.

    Together, our study highlights for the first time the influence of a hyperactive JAK2 on platelet activation-induced ADP secretion and dense granule homeostasis, with consequent effects on platelet activation properties.

    Together, our study highlights for the first time the influence of a hyperactive JAK2 on platelet activation-induced ADP secretion and dense granule homeostasis, with consequent effects on platelet activation properties.

    We aimed to characterize circulating HMGB1 (high-mobility group box-1) levels, one of the better-characterized damage-associated molecular patterns, with respect to age, sex, and race in the general population, and investigate the longitudinal associations of HMGB1 with inflammatory markers, obesity, and preclinical markers of cardiovascular disease. Approach and Results The analyses included 489 participants (50% Blacks, aged 24.6±3.3 years at the first visit) with up to 4 follow-up visits (1149 samples) over a maximum of 8.5 years. Systolic blood pressure, diastolic blood pressure, carotid-femoral pulse wave velocity, and carotid intima-media thickness together with plasma HMGB1, hs-CRP (high-sensitivity C-reactive protein), IFN-γ (interferon-γ), IL-6 (interleukin-6), IL-10 (interleukin-10), and TNF-α (tumor necrosis factor-α) were measured at each visit. At baseline, plasma HMGB1 concentrations were higher in Blacks compared with Whites (3.86 versus 3.20 ng/mL,

    <0.001), and in females compared with males (3.

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