Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>MMP-13 and IGFBP-5 are important factors involved in osteoarthritis (OA). We investigated whether two highly predicted microRNAs (miRNAs), miR-140 and miR-27a, regulate these two genes in human OA chondrocytes.</p> <p>Methods</p> <p>Gene expression was determined by real-time PCR. The effect of each miRNA on IGFBP-5 and MMP-13 expression/production was evaluated by transiently transfecting their precursors (pre-miRNAs) and inhibitors (anti-miRNAs) into human OA chondrocytes. Modulation of IGFBP-5, miR-140 and miR-27a expression was determined upon treatment of OA chondrocytes with cytokines and growth factors.</p> <p>Results</p> <p>IGFBP-5 was expressed in human chondrocytes with its level significantly lower (p < 0.04) in OA. Five computational algorithms identified miR-140 and miR-27a as possible regulators of MMP-13 and IGFBP-5 expression. Data showed that both miRNAs were expressed in chondrocytes. There was a significant reduction (77%, p < 0.01) in miR-140 expression in OA compared to the normal chondrocytes, whereas miR-27a expression was only slightly decreased (23%). Transfection with pre-miR-140 significantly decreased (p = 0.0002) and with anti-miR-140 significantly increased (p = 0.05) IGFBP-5 expression at 24 hours, while pre-miR-27a did not affect either MMP-13 or IGFBP-5. Treatment with anti-miR-27a, but not with anti-miR-140, significantly increased the expression of both MMP-13 (p < 0.05) and IGFBP-5 (p < 0.01) after 72 hours of incubation. MMP-13 and IGFBP-5 protein production followed the same pattern as their expression profile. These data suggest that IGFBP-5 is a direct target of miR-140, whereas miR-27a down-regulates, likely indirectly, both MMP-13 and IGFBP-5.</p> <p>Conclusion</p> <p>This study is the first to show the regulation of these miRNAs in human OA chondrocytes. Their effect on two genes involved in OA pathophysiology adds another level of complexity to gene regulation, which could open up novel avenues in OA therapeutic strategies.</p

The legal status of animals in Poland and the European Union

Praca ma na celu przedstawienie statusu prawnego zwierząt na poziomie polskim i unijnym. Głównym celem pracy jest ukazanie jak przepisy prawne są realizowane w praktyce i czy są skutecznym narzędziem w walce z okrucieństwem wobec zwierząt. Rozdział pierwszy poświęcony jest zagadnieniom pozycji zwierząt w życiu człowieka, rozdział drugi poświęcony jest narodzinom i specyfice ideologii ruchu praw zwierząt, rozdział trzeci i czwarty poświęcony jest kolejno zagadnieniom z zakresu prawnej ochrony zwierząt na poziomie polskim i unijnym.This work is to present the legal status of animals at the level of Polish and EU. The main aim of this work is to show how laws are implemented in practice and whether they are an effective tools in the fight against cruelty to animals. The first chapter is devoted to issues of animal status in human life, the second chapter is devoted to the birth and the specifics of the ideology of animal rights movement, the third and fourth chapter is devoted to succession issues in the field of legal protection of animals at the level of Polish and EU

Estimated Cost Effectiveness of Influenza Vaccination for Emergency Medical Services Professionals

Introduction: Because of their frequent contact with compromised patients, vaccination against influenza is recommended for all healthcare workers. Recent studies suggest that vaccination decreases influenza transmission to patients and reduces worker illness and absenteeism. However, few emergency medical services (EMS) agencies provide annual vaccination, and the vaccination rate among EMS personnel remains low. Reticence among EMS agencies to provide influenza vaccination to their employees may be due in part to the unknown fiscal consequences of implementing a vaccination program. In this study, we sought to estimate the cost effectiveness of an employer-provided influenza vaccination program for EMS personnel. Methods: Using data from published reports on influenza vaccination, we developed a cost-effectiveness model of vaccination for a hypothesized EMS system of 100 employees. Model inputs included vaccination costs, vaccination rate, infection rate, costs associated with absenteeism, lost productivity due to working while ill (presenteeism), and medical care for treating illness. To assess the robustness of the model we performed a series of sensitivity analyses on the input variables. Results: The proportion of employees contracting influenza or influenza-like illness (ILI) was estimated at 19% among vaccinated employees compared to 26% among non-vaccinated employees. The costs of the vaccine, consumables, and employee time for vaccination totaled $44.19 per vaccinated employee, with a total system cost of$4,419. Compared to no vaccination, a mandatory vaccination program would save $20,745 in lost productivity and medical costs, or$16,325 in net savings after accounting for vaccination costs. The savings were 3.7 times the cost of the vaccination program and were derived from avoided absenteeism ($7,988), avoided presenteeism productivity losses ($10,303), and avoided medical costs of treating employees with influenza/ILI ($2,454). Through sensitivity analyses the model was verified to be robust across a wide range of input variable assumptions. The net monetary benefits were positive across all ranges of input assumptions, but cost savings were most sensitive to the vaccination uptake rate, ILI rate, and presenteeism productivity losses. Conclusion: This cost-effectiveness analysis suggests that an employer-provided influenza vaccination program is a financially favorable strategy for reducing costs associated with influenza/ILI employee absenteeism, presenteeism, and medical care.&nbsp

A Handbook for using the student outcomes questionnaires : field review edition /

Accompagné de 8 questionnaire

Predictors of COVID-19 Vaccination Among EMS Personnel

Introduction: Unvaccinated emergency medical services (EMS) personnel are at increased risk of contracting coronavirus disease 2019 (COVID-19) and potentially transmitting the virus to their families, coworkers, and patients. Effective vaccines for the severe acute respiratory syndrome coronavirus 2 virus exist; however, vaccination rates among EMS professionals remain largely unknown. Consequently, we sought to document vaccination rates of EMS professionals and identify predictors of vaccination uptake.Methods: We conducted a cross-sectional survey of North Carolina EMS professionals after the COVID-19 vaccines were widely available. The survey assessed vaccination status as well as beliefs regarding COVID-19 illness and vaccine effectiveness. Prediction of vaccine uptake was modeled using logistic regression.Results: A total of 860 EMS professionals completed the survey, of whom 74.7% reported receiving the COVID-19 vaccination. Most respondents believed that COVID-19 is a serious threat to the population, that they are personally at higher risk of infection, that vaccine side effects are outweighed by illness prevention, and the vaccine is safe and effective. Despite this, only 18.7% supported mandatory vaccination for EMS professionals. Statistically significant differences were observed between the vaccinated and unvaccinated groups regarding vaccine safety and effectiveness, recall of employer vaccine recommendation, perceived risk of infection, degree of threat to the population, and trust in government to take actions to limit the spread of disease. Unvaccinated respondents cited reasons such as belief in personal health and natural immunity as protectors against infection, concerns about vaccine safety and effectiveness, inadequate vaccine knowledge, and lack of an employer mandate for declining the vaccine. Predictors of vaccination included belief in vaccine safety (odds ratio [OR] 5.5, P=&lt;0.001) and effectiveness (OR 4.6, P=&lt;0.001); importance of vaccination to protect patients (OR 15.5, P=&lt;0.001); perceived personal risk of infection (OR 1.8, P=0.04); previous receipt of influenza vaccine (OR 2.5, P=0.003); and sufficient knowledge to make an informed decision about vaccination (OR 2.4,&nbsp; P=0.024).Conclusion: In this survey of EMS professionals, over a quarter remained unvaccinated for COVID-19. Given the identified predictors of vaccine acceptance, EMS systems should focus on countering misinformation through employee educational campaigns as well as on developing policies regarding workforce immunization requirements