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Napier Craven posted an update 1 week ago
Mesothelin is a 40-kDa glycoprotein that is highly overexpressed in various types of cancers, however molecular mechanism of mesothelin has not been well-known. Amatuximab is a chimeric monoclonal IgG1/k antibody targeting mesothelin. We recently demonstrated that the combine therapy of Amatuximab and gemcitabine was effective for peritonitis of pancreatic cancer in mouse model.
We discover the role and potential mechanism of mesothelin blockage by Amatuximab in human pancreatic cells both expressing high or low level of mesothelin in vitro experiment and peritonitis mouse model of pancreatic cancer.
Mesothelin blockage by Amatuximab lead to suppression of invasiveness and migration capacity in AsPC-1 and Capan-2 (high mesothelin expression) and reduce levels of pMET expression. The combination of Amatuximab and gemcitabine suppressed proliferation of AsPC-1 and Capan-2 more strongly than gemcitabine alone. These phenomena were not observed in Panc-1 and MIA Paca-2 (Mesothelin low expression). We previously demonstrated that Amatuximab reduced the peritoneal mass in mouse AsPC-1 peritonitis model and induced sherbet-like cancer cell aggregates, which were vanished by gemcitabine. In this study, we showed that the cancer stem cell related molecule such as ALDH1, CD44, c-MET, as well as proliferation related molecules, were suppressed in sherbet-like aggregates, but once sherbet-like aggregates attached to peritoneum, they expressed these molecules strongly without the morphological changes.
Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.
Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.
Diabetes increases a patient’s risk of developing atrial fibrillation by 49%. selleck chemicals llc Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes.
This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervaan ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.
In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.
To evaluate the prevalence of work-related musculoskeletal disorders (WRMSDs) in perioperative nurses and to explore their association with personal characteristics.
Medline, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane Library and Joanna Briggs Institute Database were systematically searched. A meta-analysis calculating event rates, and relative 95% Confidence Intervals (CI) was performed for each musculoskeletal body region. The contribution of perioperative nurses’ sex, age, and BMI was assessed through a meta-regression.
Twenty-two studies, considering 3590 perioperative nurses, were included in the systematic review. The highest prevalence of WRMSDs was found for the lower-back (62%; 95% CI 0.54-0.70), followed by knee (47%; 95% CI 0.36-0.59), shoulder (44%; 95% CI 0.37-0.51), waist (42%; 95% CI 0.31-0.53), neck (39%; 95% CI 0.29-0.51), ankle-feet (35%; 95% CI 0.22-0.51), upper-back (34%; 95% CI 0.25-0.44), hand-wrist (29%; 95% CI 0.20-0.40), and elbow risk of WRMSDs in other health-care professionals’ population.
Simulation exercises can functionally validate World Health Organization (WHO) International Health Regulations (IHR 2005) core capacities. In 2018, the Vietnam Ministry of Health (MOH) conducted a full-scale exercise (FSX) in response to cases of severe viral pneumonia with subsequent laboratory confirmation for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) to evaluate the country’s early warning and response capabilities for high-risk events.
An exercise planning team designed a complex fictitious scenario beginning with one case of severe viral pneumonia presenting at the hospital level and developed all the materials required for the exercise. Actors, controllers and evaluators were trained. In August 2018, a 3-day exercise was conducted in Quang Ninh province and Hanoi city, with participation of public health partners at the community, district, province, regional and national levels. Immediate debriefings and an after-action review were conducted after all exercise activities. Participantuntry may have been better able to deal with the emergence of SARS-CoV-2 and contain it.
This exercise documents the value of exercising surveillance capabilities as part of a real-time operational scenario before facing a true emergency. The timing of this exercise and choice of disease scenario was particularly fortuitous given the subsequent appearance of COVID-19. As a result of this exercise and subsequent improvements made by the MOH, the country may have been better able to deal with the emergence of SARS-CoV-2 and contain it.
The secondary fracture prevention gap in the osteoporosis field has been previously described as a ‘crisis’. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1-2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures.
This retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017).