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The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b-6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.
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Antioxidantes/química , Antioxidantes/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Fármacos , Bases de Mannich/química , Oxidiazóis/química , Piridazinas/farmacologia , Pirróis/farmacologia , Antioxidantes/síntese química , Domínio Catalítico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Feminino , Fibroblastos/metabolismo , Humanos , Concentração Inibidora 50 , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Estrutura Molecular , Piridazinas/síntese química , Piridazinas/química , Pirróis/síntese química , Pirróis/química , Soroalbumina Bovina/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: According to data from the Organisation for Economic Cooperation and Development, Poland has one of the lowest numbers of nurses (5.2) per 1000 inhabitants among 28 EU countries. The migration of nurses from Poland has particular importance in the context of scarce human resources in this professional group, especially given the increasingly ageing population in European societies, which will entail an increased demand for nursing and care services. The aim of the study was to obtain information on the intentions of Polish nurses to migrate for work to other countries in the European region. METHODS: The study included 581 nurses, professionally active in Poland over the duration of the study. The Computer Assisted Web Interview technique was used to collect data. Nurses filled in a web-based questionnaire that was available from December 5, 2011, to March 5, 2012. The choice of respondents for the sample was based on the availability of data. An invitation to participate in the study could be viewed on selected websites from the Portal of Nurses and Midwives, the Supreme Chamber of Nurses and Midwives, and the Polish Nursing Society. The survey questionnaire was designed by the authors, which served as the primary research tool. RESULTS: Nearly one in three respondents intended to leave Poland for professional reasons. Overall, 12.4 % of respondents had already worked as a nurse abroad. The main destinations for migration included Germany, followed by England and Norway. The intended length of stay abroad ranged from 2-5 years. CONCLUSIONS: In the studied group of Polish nurses, there was great interest in seeking employment abroad. Nurses tend to go abroad mostly for long-term, repeated periods to the wealthiest countries nearest to Poland. In view of the low level of human resources in the Polish nursing sector, the migration of Polish nurses will probably have crucial implications for the quality of healthcare services in Poland in the coming years. Given the methodology applied, study findings refer solely to the study group.
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Emigração e Imigração , Intenção , Enfermeiras e Enfermeiros , Área de Atuação Profissional , Adulto , Europa (Continente) , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/provisão & distribuição , Polônia , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to determine how often patients and undiagnosed people who complain of musculoskeletal system and rheumatic diseases look for knowledge contained on an Internet forum. Content analysis was used to identify the level of Internet users' activity in the rheumatology section, compared to other areas of medicine. MATERIAL AND METHODS: Material included information posted on the Internet forum established at http://medyczka.pl/. The method employed was a quantitative and qualitative analysis of the content. The method was based on qualitative assessment of the first post in each thread presented on the rheumatologic subforum, by assigning keywords, subjectively determined by the researcher, to such a post. For each keyword a specific definition was established, determining a situation in which a given keyword was used. RESULTS: The quantitative analysis qualified rheumatology in the last place in terms of Internet users' activity compared to other branches of medicine. The qualitative assessment of the rheumatologic forum indicated that the three most common keywords were joint pain (32), joints swelling (13), and schoolage (13). The three most common intentional keywords (arranged in order of their decreasing number) were diagnosis based on symptoms (29), interpretation of the laboratory test results (9), and how to deal with symptoms (8). CONCLUSIONS: The analysis leads to the conclusion that the rheumatologic subforum, along with other subforums listed above, presents a critically low level of discussion. There is a large disproportion between the number of active and passive forum users, suggesting that numerous individuals search the forum for presented information. Based on the qualitative analysis of the information stocks of the rheumatologic subforum, it was established that most of the questions posted concerned young individuals, who complained of joint pain and swelling, and asked for a possible diagnosis based on the presented symptomatology, interpretation of the laboratory test results and alleviation of disease symptoms.
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Introduction: Coronavirus disease 2019 (COVID-19) exacerbates intravascular thrombosis that occurs in the coronary artery in ST-elevation myocardial infarction (STEMI). Aim: To analyze the impact of COVID-19 on the application and effect of thrombectomy in STEMI patients. Material and methods: 29915 STEMI patients were analyzed, of whom 3139 (10.5%) underwent thrombectomy. COVID-19 (+) was reported in 311 (10.8%). The clinical characteristics and management of STEMI in COVID-19 (+) and COVID-19 (-) patients were compared. A multivariable logistic regression analysis was performed in search of factors influencing thrombectomy. Results: COVID-19 (+) patients had higher Killip class (IV class; n = 33 (12.31%) vs. n = 138 (5.84%); p < 0.0001) and cardiac arrest at baseline was more frequent in this group (n = 25 (8.04%) vs. n = 137 (4.84%); p = 0.016). Thrombolysis in myocardial infarction (TIMI) 3 after percutaneous coronary intervention was less frequent (n = 248 (80.52%) vs. n = 2388 (87.19%); p = 0.001) in the COVID-19 (-) group. Periprocedural mortality was similar in both groups (n = 28 (0.99%) vs. n = 4 (1.29%); p = 0.622). In multivariable regression analysis COVID-19 increased the risk of thrombectomy (OR = 1.23; 97.5% CI: 1.05-1.43; p = 0.001). Conclusions: STEMI patients undergoing aspiration thrombectomy who were COVID-19 (+) were more likely to be in a severe clinical condition (higher Killip class, more frequent cardiac arrest before the procedure) than COVID-19 (-) patients. Despite more intensive antiplatelet and anticoagulant treatment, PCI procedures were less likely to result in an optimal TIMI 3 effect. COVID-19 is an independent strong predictor of patient qualification for aspiration thrombectomy in STEMI.
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INTRODUCTION: Many factors related to the switch to summer/winter time interfere with biological rhythms. OBJECTIVES: This study aimed to analyze the impact of time change on clinical outcomes of patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Electronic data of 874,031 patients with ACS who underwent invasive procedures were collected from the Polish National Register of Interventional Cardiology Procedures (ORPKI) between 2014 and 2021. We determined the number of patients undergoing PCI and periprocedural mortality during the day of spring or autumn time change and within the first 3 and 7 days after the time change. RESULTS: We demonstrated the impact of time changes on the periprocedural mortality of ACS patients within 1 day and the period of 3 and 7 days from the time change. We observed that the occurrence of all ACS and NSTEMI on the first day was lower for both time changes and higher in the case of UA and spring time change. The autumn time change significantly reduced the occurrence of all types of ACS. A significant decrease in the number of invasive procedures was found after autumn transition in the period from the first day to 7 days for ACS, NSTEMI, and UA. CONCLUSIONS: The occurrence of ACS and the number of invasive procedures were lower for both changes over time. Autumn time change is associated with increased periprocedural mortality in ACS and a less frequent occurrence of UA and NSTEMI within 7 days.
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An impaired fibrinolytic process has been demonstrated in patients infected with SARS-CoV-2, including those in severe or critical condition. Disruption of fibrinolysis leads to fibrin deposition, which exacerbates inflammation and fibrosis and damages the pulmonary surfactant. Numerous authors point out the different course of coagulopathy in patients with COVID-19. It is reported that they may have a state of secondary hyperfibrinolysis, which may explain, at least in part, the increased incidence of venous thromboembolism, even among those patients already receiving appropriate anticoagulant treatment. This raises the question of whether current guidelines for the prevention and treatment of embolic-thrombotic complications, among patients with severe COVID-19, are sufficient. Some studies show evidence of clinical improvement in patients who have received fibrinolytic therapy, beyond the current indications for its implementation. However, when considering the inclusion of systemic fibrinolytic therapy, the benefits of such treatment should always be weighed over the risk of adverse effects. Thromboelastography and rotational thromboelastometry can be helpful in making such decisions. The purpose of this study was to review the current knowledge regarding fibrinolysis and its role in the treatment of patients with severe COVID-19, including those with thromboembolic complications.
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COVID-19 causes thromboembolic complications that affect the patient's prognosis. COVID-19 vaccines significantly improve the prognosis for the course of the infection. The aim of this study was to evaluate the impacts of patient characteristics, including COVID-19 vaccinations, on perioperative mortality in acute coronary syndrome in Poland during the pandemic. We analyzed the data of 243,515 patients from the National Registry of Invasive Cardiology Procedures (Ogólnopolski Rejestr Procedur Kardiologii Inwazyjnej [ORPKI]). In this group, 7407 patients (21.74%) had COVID-19. The statistical analysis was based on a neural network that was verified by the random forest method. In 2020, the most significant impact on prognosis came from a diagnosis of unstable angina, a short period (<2 h) from pain occurrence to first medical contact, and a history of stroke. In 2021, the most significant factors were pre-hospital cardiac arrest, female sex, and a short period (<2 h) from first medical contact to coronary angiography. After adjusting for a six-week lag, a diagnosis of unstable angina and psoriasis were found to be relevant in the data from 2020, while in 2021, it was the time from the pain occurrence to the first medical contact (2−12 h) in non-ST segment elevation myocardial infarction and the time from first contact to balloon inflation (2−12 h) in ST-segment elevation myocardial infarction. The number of vaccinations was one of the least significant factors. COVID-19 vaccination does not directly affect perioperative prognosis in patients with acute coronary syndrome.
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OBJECTIVE: The aim of the study was to determine and compare the prevalence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) antibodies and DNA among nurses working in different profiles of healthcare activity. MATERIAL AND METHODS: The study population comprised 120 women (90 exposed healthcare workers and 30 controls). Blood samples were investigated using chemiluminescent microparticle immunoassays (CMIA) tests to detect the presence of EBV VCA IgM, IgG, and CMV IgM, IgG. Plasma CMV and EBV DNA levels were assessed using real-time polymerase chain reaction (PCR). RESULTS: CMV IgG antibodies were present in 87.80% nurses (86.70% in controls), EBV IgG were present in all the nurses studied and in the control group. No statistically significant differences were noted between the subgroups of nurses and the control group as regards IgG CMV, VCA IgG EBV. CMV IgM/EBV IgM antibodies were negative in all the nurses. CMV/EBV DNA was reported only in the study group. It was not found in any of control group participants. CONCLUSIONS: The positive PCR CMV/EBV markers only in the study group can be indicative of the exposure of nurses to these pathogens being greater than in other people not being professionally involved in patient care. In addition, it was observed that the level of CMV IgG antibodies as well as EBV VCA IgG antibodies tended to be linked to the age and the length of work of nurses working in pediatrics.