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Background and Aim: With the emergence of severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), antiviral drug development has gained increased significance due to the high incidence and potentially severe complications of the resulting coronavirus infection. Heterocycle compounds, acting as antimetabolites of DNA and RNA monomers, rank among the most effective antiviral drugs. These compounds' antiviral effects on various SARS-CoV-2 isolates, as found in existing data collections, form the basis for further research. The aim of this study was to examine the possible antiviral effect of some originally synthesized heterocyclic compounds. Materials and Methods: The main methods were cell culturing, cytotoxicity assay, qRT-PCR assay, tissue and blood cells analysis, and micro-computed tomography (micro-CT) imaging. Results: In both in vitro and in vivo conditions, the elimination of SARS-Cov-2 occurred significantly earlier after administration of the compounds compared to the control group. In hamsters, the primary symptoms of coronavirus disease disappeared following administration of heterocycle compounds. Conclusion: Using delta and omicron strains of the SARS-CoV-2 virus, newly created heterocycle compound analogs dramatically reduced SARS-CoV-2 multiplication, resulting in a drop in viral RNA load in the supernatant under in vitro conditions. Improvements in pathological manifestations in the blood, bone marrow, and internal organs of hamsters demonstrated that heterocycle compounds inhibited SARS-CoV-2 replication both in vitro and in vivo.
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Payment mechanisms have attracted substantial research interest because of their consequent effect on care outcomes, including treatment costs, admission and readmission rates and patient satisfaction. Those mechanisms create the incentive environment within which health workers operate and can influence provider behaviour in ways that can facilitate achievement of national health policy goals. This systematic review aims to understand the effects of changes in hospital payment mechanisms introduced in low- and middle-income countries (LMICs) on hospital- and patient-level outcomes. A standardised search of seven databases and a manual search of the grey literature and reference lists of existing reviews were performed to identify relevant articles published between January 2000 and July 2019. We included original studies focused on hospital payment reforms and their effect on hospital and patient outcomes in LMICs. Narrative descriptions or studies focusing only on provider payments or primary care settings were excluded. The authors used the Risk of Bias in Non-Randomized Studies of Interventions tool to assess the risk of bias and quality. Results were synthesized in a narrative description due to methodological heterogeneity. A total of 24 articles from seven middle-income countries were included, the majority of which are from Asia. In most cases, hospital payment reforms included shifts from passive (fee-for-service) to active payment models-the most common being diagnosis-related group payments, capitation and global budget. In general, hospital payment reforms were associated with decreases in hospital expenditures, out-of-pocket payments, length of hospital stay and readmission rates. The majority of the articles scored low on quality due to weak study design. A shift from passive to active hospital payment methods in LMICs has been associated with lower hospital and patient costs as well as increased efficiency without any apparent compromise on quality. However, there is an important need for high-quality studies in this area.
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Países em Desenvolvimento , Planos de Pagamento por Serviço Prestado , Custos e Análise de Custo , Hospitais , Humanos , MotivaçãoRESUMO
BACKGROUND: Non-communicable diseases account for a growing proportion of deaths in Armenia, which require early detection to achieve disease control and prevent complications. To increase rates of screening, demand-side interventions of personalized invitations, descriptive social norms, labeled cash transfers, and conditional cash transfers were tested in a field experiment. Our complementary qualitative study explores factors leading to the decision to attend screening and following through with that decision, and experiences with different intervention components. METHODS: Informed by the Health Belief Model as our conceptual framework, we collected eighty in-depth interviews with service users and twenty service providers and analyzed them using open coding and thematic analysis. RESULTS: An individual's decision to screen depends on 1) the perceived need for screening based on how they value their own health and perceive hypertension and diabetes as a harmful but manageable condition, and 2) the perceived utility of a facility-based screening, and whether screening will provide useful information on disease status or care management and is socially acceptable. Following through with the decision to screen depends on their knowledge of and ability to attend screenings, as well as any external motivators such as an invitation or financial incentive. CONCLUSIONS: Personalized invitations from physicians can prompt individuals to reconsider their need for screening and can, along with financial incentives, motivate individuals to follow through with the decision to screen. The effect of descriptive social norms in invitations should be further studied. Efforts to increase preventive screenings as an entry point into primary care in Armenia may benefit from implementation of tailored messages and financial incentives. TRIAL REGISTRATION: The protocol was approved on January 11, 2019 by the Institutional Review Board of the Center of Medical Genetics and Primary Health Care in Armenia (02570094). https://www.socialscienceregistry.org/trials/3776 .
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Comportamentos Relacionados com a Saúde , Programas de Rastreamento/economia , Motivação , Atenção Primária à Saúde/economia , Reembolso de Incentivo/economia , Armênia , Economia Comportamental , Humanos , Entrevistas como Assunto , Programas de Rastreamento/métodos , Doenças não Transmissíveis , Pesquisa QualitativaRESUMO
The purpose of the present study is to investigate the effect of mesenchymal stem cells in corneal neovascularization and wound healing, and to compare the effectiveness of two possible application routes, subconjunctival injection and amniotic membrane transplantation. Chemical injury was induced by application of sodium hydroxide to the rats' corneas. After 7 days, the animals were divided into three groups. Different treatment methods were used for each group as follows: i) Group 1, injection of bone marrowderived mesenchymal stem cells (BMSCs) under the conjunctiva; ii) group 2, transplantation of amniotic membranes, previously seeded with BMSCs; and iii) group 3, the untreated control group. The eyes were examined using a slit lamp on a weekly basis. After 4 weeks, the animals were sacrificed and corneas were removed for further examination. Corneal flat mounts were made following ink perfusion for improved vessel visualization, image capturing and quantitative evaluation. enzymelinked immunosorbent assay was performed to detect the levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9). Reverse transcriptionquantitative polymerase chain reaction was used for detection of VEGFA, MMP9, Tolllike receptor (TLR)2 and TLR4 gene expression levels. Cryosections were used for histological examination and immunostaining. Statistical analysis (Welch's oneway analysis of variance) demonstrated a significant difference between the groups [P≤0.05, confidence interval (CI) 95%]. The level of injury in group 1 was significantly different from groups 2 and 3. Measurement of the vessel area and VEGF gene expression levels had a similar difference among the groups (P≤0.05, CI 95%), however the differences for TLR2 and TLR4 were not statistically significant. BMSCs were previously transduced with the green fluorescent protein gene by lentivirus to track the movement of the cells following transplantation. The transplanted cells enhanced corneal wound healing by trophic factor production and immuneregulatory effect, rather than by direct transdifferentiation into corneal cells. The results of the current study demonstrated that BMSCs enhance corneal wound healing and decrease the area of neovascularization. Furthermore, the comparison of two application routes indicated that single subconjunctival injection appeared more effective than transplantation with amniotic membrane.
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Córnea/irrigação sanguínea , Neovascularização da Córnea/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Animais , Técnicas de Cultura de Células , Separação Celular , Células Cultivadas , Córnea/metabolismo , Córnea/patologia , Neovascularização da Córnea/genética , Neovascularização da Córnea/patologia , Feminino , Expressão Gênica , Células-Tronco Mesenquimais/metabolismo , Ratos Wistar , Transdução Genética , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive loss of photoreceptors and eventually leads to retina degeneration and atrophy. Until now, the exact pathogenesis and etiology of this disease has not been clear, and many approaches for RP therapies have been carried out in animals and in clinical trials. In recent years, stem cell transplantation-based attempts made some progress, especially the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs). This review will provide an overview of stem cell-based treatment of RP and its main problems, to provide evidence for the safety and feasibility for further clinical treatment.