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    Opioids/cannabinoids as a potential therapeutic approach in COVID-19 patients

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    Toxicity of Saffron Extracts on Cancer and Normal Cells: A Review Article

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    BACKGROUND AND AIM: Medicinal plants have played an important role in human health since the Stone Age. According to WHO, 80 of Asian and African people rely on traditional medicine and medicinal plants to conserve their health. Saffron has received much attention among the herbal compounds related to cancer treatment. METHODS: This review aims to provide an overview of in-vitro and in-vivo evaluation molecule mechanism for anti-tumor activity, cancer preventing and protective effects of saffron extract. The review is based on the available data accessible in PubMed, Science Direct, Google Scholar, Magiran.ir, and SID.ir databases. RESULTS: Saffron has selective toxic and preventive effects on cancerous cells and without adverse effects on normal cells and prevents tumor formation. Saffron appears to reduce the toxic effects of anticancer drugs. Saffron has toxicity effects when used in high amounts, which are far greater than those are used in human food culture. CONCLUSIONS: Considering the observed effects of saffron on the removal of cancer cells, saffron extract can be used in the treatment and prevention of cancer after confirmation in human clinical trials. According to the high IC50 of saffron extracts in normal cells, its toxicity against non-cancerous cells is low and its use is safe. Besides, the studies suggested the cytotoxic effects of saffron on some of the more cancers, including nervous system cancer and common cancers. Further studies are required to determine the effective dose and influence of mechanism of saffron in various animal type of cancers

    Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study

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    Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9) patients had a stroke�123(79) ischaemic stroke, 27(17) intracerebral/subarachnoid hemorrhage, and 6(4) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5 among all centres in all countries, and 0.7 among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95 CI:1.1�3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95 CI:1.4�4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5(pooled risk: 0.9). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding: None. © 2020 The Author

    Ab Initio Study of TEPA Adsorption on Pristine, Al and Si Doped Carbon and Boron Nitride Nanotubes

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    The present first principles study entails the adsorption behavior of N, Nʹ, Nʺ-triethylenephosphoramide (TEPA) drug over the pristine, Si- and Al-doped (5, 5) armchair single-wall carbon and boron-nitride nanotubes (SWCNTs and SWBNNTs). Density functional theory (DFT) calculations were done via the B3LYP and M06-2X methods with the standard 6-31G** basis set. The results show that the adsorption of TEPA drug molecule occurred physically on pristine CNT and BNNT and chemically on Al- and Si-doped CNTs and BNNTs. Although Si- and Al-doped CNTs and Al-doped BNNT provide stronger adsorption, the change in the energy gap of the Si-doped BNNT was more pronounced. The lipophilicity calculations indicated that the pure, Si- and Al-doped BNNTs are better candidates for increasing the efficiency of TEPA drug. It has been predicted that the Si-doped BNNT may be a promising drug delivery agent. © 2020, Springer Science+Business Media, LLC, part of Springer Nature

    Advanced sequence optimization for the high efficient yield of human group A rotavirus VP6 recombinant protein in Escherichia coli and its use as immunogen

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    Rotavirus is the important etiological agents of infectious diarrhea among children under 5 years old. Rotaviruses are divided into 10 serogroups (A�J) and each group is based on genetic properties of major structural protein VP6. We designed a novel VP6 sequence optimization to increase the expression level of this protein. Numerous factors such as codon adaptation index, codon pair bias, and guanine-cytosine content were adapted based on Escherichia coli codon usage. In addition, the ribosome binding site (RBS) of pET-15b was redesigned by the RBS calculator and the secondary structure of VP6 messenger RNA was optimized in the whole length of the coding sequence. Various factors including isopropyl beta-d-thiogalactoside (IPTG) concentration, temperature, and induction time were analyzed for the optimization of the best expression in E. coli by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. The recombinant VP6 (rVP6) protein was purified by the Ni-sepharose and then the hyperimmune sera were generated against rVP6 in rabbits. Among three different temperatures, IPTG concentrations, and postinductions, the level of rVP6 was higher at 37°C, 1 mM of IPTG, and 8 h, respectively. Also, the high expression level of rVP6 was obtained in the insoluble aggregate form (43.8 g/L). After purification, the yield of rVP6 was 10.83 g/L. The rVP6 specific antiserum was confirmed by both immunofluorescent and western blotting. The versatile sequence optimization was the reason to produce a high level of rVP6 compared to other reports and can potentially apply to produce cheaper commercial kits to diagnose serological tests and new rotavirus vaccines. © 2020 Wiley Periodicals LL

    Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype

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    Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. Objective: We evaluated sex-specific and onset phenotype�specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype�specific MSSS matrices. We compared matrices using permutation analysis. Results: Our final dataset included 30,203 MS cases, with 28.9 males and 6.5 progressive-onset cases. Our global MSSS matrix did not differ from previously published data (p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix (p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex. Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts. © The Author(s), 2019

    Global burden of 369 diseases and injuries in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

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    Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990�2010 time period, with the greatest annualised rate of decline occurring in the 0�9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10�24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10�24 years were also in the top ten in the 25�49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50�74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

    Relationship Between the Distribution and Biodiversity of Sand Flies (Diptera: Psychodidae) With the Incidence of Zoonotic Cutaneous Leishmaniasis in Endemic Foci of Golestan Province, Iran

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    Zoonotic cutaneous leishmaniasis (ZCL) is prevalent in Golestan Province, Iran. The current study determined the relationship between the distribution and biodiversity of sand flies with cutaneous leishmaniasis at 14 villages in plain and hillsides areas. In each village from July to September 2017, 60 sticky traps and 2 CDC light traps were laid. Spearman and Mann-Whitney tests were used to determine the relationship between the incidence of ZCL and the abundance of different species of sand flies. Simpson, Shannon-Wiener, Evenness, and Margalef indices were calculated to estimate the diversity of species. A total of 5,295 phlebotomine sand flies were collected, comprising 10 species of the genus Phlebotomus (3,947 flies) and 7 species of genus Sergentomyia (1,248 flies). The abundance of sand flies and incidence of ZCL in plain areas were greater than that of hillsides areas (P = 0.013, P = 0.002). There was a significant correlation between the incidence of ZCL and the abundance of Phlebotomus papatasi (r = 0.72, P = 0.004) and P. caucasicus groups (P = 0.006; 0.022). In the Shannon-Wiener index, the rest of the biodiversity indices were reduced in higher-altitude areas. Increasing Shannon-Wiener index showed higher diversity of sand flies in higher-altitude areas. Data of the reported cases of leishmaniasis in plain areas can reveal the relationship between less diversity index (Shannon-Wiener), higher dominant diversity index (Simpson), and incidence of leishmaniasis in these areas. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: [email protected]

    Biochemical parameters and pathogenesis of SARS-CoV-2 infection in vital organs: COVID-19 outbreak in Iran

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    Since its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, and led to ever-increasing mortality. SARS-CoV-2 infection perturbs the function of the body's vital organs, making patients of all ages susceptible to the disease. Nevertheless, individuals developing critical illness with poor outcomes were mostly the elderly and people with co-morbid conditions, who constituted the vast majority of coronavirus disease 2019 (COVID-19) fatalities. Complications of COVID-19 mostly involve the respiratory, renal and cardiovascular systems, and in severe cases secondary infections leading to pneumonia and acute respiratory distress syndrome, which may precede the death of the patient. Multi-organ failure in individuals with COVID-19 could be a consequence of their co-morbidities. A patient's pre-existing conditions may affect the disease prognosis, requiring immediate attention to accurately detect and evaluate them in SARS-CoV-2-infected individuals. This review addresses several issues in relation to manifestations of the body's vital organs along with potential diagnostic blood factors in SARS-CoV-2 infection. It is hoped that the review will lead to more comprehensive understanding of this complex disease. © 2020 The Author

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