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Abstract Background The burden of disease based on disability-adjusted life years (DALYs) is one of the internationally accepted metrics for assessing the impact of a disease or injury on population health. This study aimed to provide evidence of the burden of COVID-19 on health in Iran based on hospital-level data from the Iran Health Insurance Organization (IHIO), which covers almost half of the country’s population. Methods The data of all IHIO enrollees who were referred to hospitals across the country from the beginning of the COVID-19 pandemic (February 2020) to December 30, 2021, with assigned diagnosis codes of COVID-19, were extracted from the hospital information processing system. The DALYs due to COVID-19 were estimated using the standard approach of the World Health Organization and the European Burden of Disease Network guideline. Results In the years 2020 and 2021, among a population of about 42 million people, 1,040,367 individuals were admitted to the hospital due to COVID-19 infection, of whom 73% were hospitalized (760,963 patients). The total estimated DALYs for these two years were 665,823 and 928,393, respectively (1,603 and 2,234 per 100,000 population). 99.7% of DALYs were attributed to years of life lost due to premature death (YLLs). The share of the disease burden in the age groups of under 20 years, 20–49 years, 50–80 years, and over 80 years was 6.6%, 26.4%, 58.4%, and 8.6%, respectively. Conclusions Based on the hospital-level data estimates, COVID-19 has had a significant burden on health in Iran. COVID-19 was identified as the fifth leading cause of disease burden in Iran during the study period, ranking after cardiovascular diseases, psychological disorders, neoplasms, and musculoskeletal disorders. Additionally, COVID-19 was the third major cause of death, following cardiovascular diseases and neoplasms. Policymaking and the implementation of comprehensive programs to enhance the response of the health system and society to outbreaks of emerging and re-emerging infectious diseases are of utmost importance.

The use of passive immunotherapy, either as plasma or purified antibodies, has been recommended to treat the emerging infectious diseases (EIDs) in the absence of alternative therapeutic options. Here, we compare the neutralization potency of various passive immunotherapy approaches designed to provide the immediate neutralizing antibodies as potential EID treatments. To prepare human plasma and purified IgG, we screened and classified individuals into healthy, convalescent, and vaccinated groups against SARS-CoV-2 using qRT-PCR, anti-nucleocapsid, and anti-spike tests. Moreover, we prepared purified IgG from non-immunized and hyperimmunized rabbits against SARS-CoV-2 spike protein. Human and rabbit samples were used to evaluate the neutralization potency by sVNT. All vaccinated and convalescent human plasma and purified IgG groups, as well as purified IgG from hyperimmunized rabbits, had significantly greater levels of spike-specific antibodies than the control groups. Furthermore, when compared to the other groups, the purified IgG from hyperimmunized rabbits exhibited superior levels of neutralizing antibodies, with an IC50 value of 2.08 μg/ml. Additionally, our results indicated a statistically significant positive correlation between the neutralization IC50 value and the positive endpoint concentration of spike-specific antibodies. In conclusion, our study revealed that purified IgG from hyperimmunized animals has greater neutralization potency than other passive immunotherapy methods and may be the most suitable treatment of critically ill patients in EIDs.

BackgroundDifferent medication prescription patterns have been associated with varying course of disease and outcomes in COVID-19. Health claims data is a rich source of information on disease treatment and outcomes. We aimed to investigate drug prescription patterns and their association with mortality and hospitalization via insurance data for a relatively long period of the pandemic in Iran.MethodsWe retrieved hospitalized patients’ data from Iran Health Insurance Organization (IHIO) spanning 26 months (2020–2022) nationwide. Included were patients with ICD-10 codes U07.1/U07.2 for confirmed/suspected COVID-19. A case was defined as a single hospitalization event for an individual patient. Multiple hospitalizations of a patient within a 30-day interval were aggregated into a single case, while hospitalizations with intervals exceeding 30 days were treated as independent cases. The Anatomical Therapeutic Chemical (ATC) was used for medications classification. The two main study outcomes were general and intensive care unit (ICU) hospitalization periods and mortality. Besides, various demographic and clinical associate factors were analyzed to derive the associations with medication prescription patterns and study outcomes using accelerated failure time (AFT) and logistic regression models.ResultsDuring the 26 months of the study period, 1,113,678 admissions with COVID-19 diagnosis at hospitals working in company with IHIO were recorded. 917,198 cases were detected from the database, among which 51.91% were females and 48.09% were males. Among the main groups of medications, antithrombotics (55.84% [95% CI: 55.74–55.94]), corticosteroids (54.14% [54.04–54.24]), and antibiotics (42.22% [42.12–42.32]) were the top used medications among cases with COVID-19. Investigation of the duration of hospitalization based on main medication groups showed antithrombotics (adjusted median ratio = 0.94 [0.94–0.95]) were significantly associated with shorter periods of overall hospitalization. Also, antithrombotics (adjusted odds ratio = 0.74 [95%CI, 0.73–0.76]), corticosteroids (0.97 [0.95–0.99]), antivirals (0.82 [0.80–0.83]), and ACE inhibitor/ARB (0.79 [0.77–0.80]) were significantly associated with lower mortality.ConclusionOver 2 years of investigation, antithrombotics, corticosteroids, and antibiotics were the top medications for hospitalized patients with COVID-19. Trends in medication prescription varied based on various factors across the country. Medication prescriptions could potentially significantly impact the trends of mortality and hospitalization during epidemics, thereby affecting both health and economic burdens.

Background and purpose: Red Cell Distribution Width (RDW) is a parameter that measures changes in red blood cell size reported in a complete blood count test. In this study, we aimed to identify the association between RDW and hypertension in Tabari cohort population. Materials and methods: In this case-control study, case group included all patients with hypertension (n= 2281) participating in Tabari Cohort Study with systolic and diastolic blood pressures more than or equal to 140 and 90, respectively, or those previously diagnosed with hypertension who received antihypertensive drugs. The control group was randomly selected from the Tabari cohort population and matched for sex, age and body mass index. Finally, 2227 people were included in each group. Blood samples were taken from all participants after 12 hours of fasting. Results: Findings showed significant differences between the two groups in all variables studied, including place of residence, level of education, socio-economic status, waist circumference, smoking, and cholesterol level (P0.05). Conclusion: Our study showed that RDW has no predictive role in hypertension and there is no significant pattern between the range of RDW and hypertension.

Abstract Aims/Introduction In recent years, mesenchymal cellular therapies have received much attention in the treatment of diabetes. In this meta‐analysis, we aimed to evaluate the efficacy of mesenchymal stem cell therapy in type 2 diabetes mellitus patients. Materials and Methods A comprehensive literature search was carried out using PubMed, Scopus, Web of Science and Central databases. A total of 1,721 articles were identified, from which nine full‐text clinical trials were qualified to enter the current meta‐analysis. The assessment groups included patients with type 2 diabetes, and levels of C‐peptide, glycosylated hemoglobin and insulin dose were analyzed before and after mesenchymal stem cell infusion. Data analysis was carried out in Stata version 11, and the Jadad Score Scale was applied for quality assessment. Results Changes in levels of C‐peptide after mesenchymal stem cell therapy were: standardized mean difference 0.20, 95% confidence interval −0.61 to 1.00, glycosylated hemoglobin levels were: standardized mean difference −1.45, 95% confidence interval −2.10 to −0.79 and insulin dose were: standardized mean difference −1.40, 95% confidence interval −2.88 to 0.09. Conclusions This meta‐analysis of prospective studies showed associations between mesenchymal stem cell therapy and control of glucose level in patients with type 2 diabetes.

Background: Cancer is a significant public health problem. Some studies indicated the anti-cancer effects of mesenchymal stem cells. These effects are related to stem cells or secretory mediator of them. The aim of this study was to evaluate the impact of condition medium of mesenchymal stem cells on A549 and JEG3 cancer cell lines. Methods: In an experimental study, A549 and JEG3 cell lines provided and grown in the culture media of DMEM F12 containing 10% fetal bovine serum were then treated with different percentages of condition medium of mesenchymal stem cells (5, 10, 20, 40, 50, and 100) for 48 hours. Metabolic activity was evaluated by MTT assay in compare to untreated cells (control). Results: MTT assay showed that various percentages of condition medium of mesenchymal stem cell had inhibitory effects on A549 cell line. Significant differences were observed between treated cells to control (p

Background and purpose: The relationship between obesity and the risk of breast cancer has been highlighted in some studies. This research aimed at studying the association between anthropometric indices and breast cancer based on enrolment phase (cross-sectional phase) data in Tabari cohort study. Materials and methods: In this cohort, 51 cases of breast cancer were recorded which were considered as the case group. Also, 153 individuals (without any type of cancer) from Tabari cohort population were randomly selected as control group. Data analysis was performed applying independent t-test, chi-square, and multivariate logistic regression. Results: The frequency of waist circumference ≥88 cm in case group was slightly lower than that of the control group (74.5% vs. 75.2%, P= 0.926). In case group, the frequency of waist to hip ratio (less than 0.85) was lower than that of the control group (70.6% vs. 80.4%, P= 0.144). The risk of breast cancer was found to be higher in rural population (OR: 8.28, P

Background and purpose: Today, increased rate of demand for insulin is predictable due to increasing cases of diabetics in the world. Therefore, it is necessary to develop economic approaches and increasing the production of insulin for the future and medicinal plants could be regarded as a promising prospect for insulin production. Materials and methods: The Allium ursinum and Silybum marianum were collected. Each herbarium was identified in School of Pharmacy affiliated with Mazandaran University of Medical Sciences and the extract was used by percolation with 70% ethanol extraction, after the solvent was evaporated by using the rotary. After the successful isolation of mesenchymal stem cells (MSCs), Wharton's jelly was derived and approved. Then, the mesenchymal stem cells were differentiated to pancreatic beta cells with two herbal extracts. Results: Compared with the control group, there was a significant difference between the levels of insulin in the culture medium obtained from the two plants (P= 0.0001). In addition, via specific dithizone staining, the insulin producing cells (IPCs) were proven. Conclusion: The extracts of Allium ursinum and Silybum marianum were found capable in inducing differentiation of the mesenchymal stem cells derived from Wharton's jelly into IPCs. Allium ursinum was seen with the highest rate of insulin production, while Silybum marianum had the lowest rate of insulin production, therefore, Allium ursinum could be more effective in treatment of diabetes.

Background: White Blood Cells (WBC) can be a useful marker to predict diabetes. In this study, we aimed to investigate the association between WBC count with type 2 diabetes in a large-scaled population-based cohort study. Methods: In the present study we used a subset of data collected in enrolment phase of Tabari cohort study. Participants with fasting blood glucose ≥126 or those who report as having diabetes or taking glucose-lowering medications were selected as case group (1765 participants) and control group included participants who did not report as having diabetes (1765 participants) and they randomly selected from the baseline population. Hematology indices were measured for all participants using Celltac Alpha MEK-6510 K. Chi-squared and independent t-test were used to compare categorical and continuous variables, respectively. Results: The mean of WBC in diabetic patients and control group was 6.89 ± 1.67 and 6.37 ± 1.49 respectively (P ≤ 0.001). The odds of diabetes based on WBC count in crud model was 1.23 [CI 95% 1.181.28] and after adjustment for all possible confounding factor was 1.17 [CI 95% 1.111.23]. Conclusions: Results of the present study showed a significant association between WBC count and diabetes. This association remained significant after adjustment for all possible confounders.

Background: Diabetes caused by insulin production disturbance is considered as the most common metabolic disorder all over the world. Diabetes may outbreak because of low insulin secretion by Islets of Langerhans β-cells, insulin resistance or both of them. In this way, using stem cells, which have the capability to differentiate into Pancreatic β-cells, is one of novel methods in this field. MSCs are the most important candidates for cellular therapy. Materials and Methods: Insulin level was examined using ELIZA method. In order to examine the morphology of differentiated cells, they were stained by Dithizone. Insulin-producer cells are cells which turn into red as a result of staining. Specific gene involving insulin-producing cells was evaluated by Real Time-PCR method. Results: The ELISA results showed that the treated cells secreted more insulin than the control group. Moreover, we found differentiation of MSCs toward insulin-secreting cells. In order to evaluate insulin production in clusters on day 21 of differentiation, we used dithizone (DTZ) staining. PDX-1 gene was confirmed by RT- PCR analysis. Conclusion: In this study, we differentiated MSCs into insulin-producing cells in vitro. It is concluded that MSCs may be considered as an excellent candidate in β-cell therapy in diabetes patients.

Wharton`s jelly-derived mesenchymal stem cells (WJ-MSCs), have a high proliferation valency and they do not produce teratogen or carcinogen after subsequent transplantation. They are known as regenerative medicine. Thus more research is needed on the isolation and characterization of mesenchymal stem cells. In this experimental study, we obtained Wharton's jelly tissues from mothers during normal vaginal delivery, after obtaining their informed consent. Mesenchymal stem cells were isolated from cultured Wharton`s jelly, cultured, and were then examined for their proliferation, immunophenotypes, and differentiation capacities. The immunophenotypes of WJ-MSCs were analyzed by flow cytometry. Differentiation was performed resulting in osteogenic, chondrogenic and adipogenic cells. WJ-MSCs formed a homogenous monolayer of adherent spindle-shaped cells. Our results showed the high capacity of the proliferation of WJ-MSCs. Immunophenotyping further confirmed the purity of the isolated cells; their surface antigen expression showed the phenotypical properties like those of WJ-MSCs. The expanded cells were positive for CD 90, CD105, and CD44; they were negative for CD34 and HLA-DR surface markers. The cells had the adipocytic, osteocytic and chondrogenic differentiation capacity. The isolation and characterization of WJ-MSCs with high purity had been conducted, and the results were obtained in a short span. The present study has revealed the feasibility of the culture medium with high glucose and 15% FBS in isolation and proliferation of WJ-MSCs. When Wharton`s jelly pieces were put in the dry bottom of the flask, very effective separation of the MSCs was achieved.

The immunotolerant human leukocyte antigen-G (HLA-G) molecules have a major role in fetal-maternal tolerance during pregnancy. Interaction between these molecules and uterine natural killer (uNK) cells inhibitory receptors prevents NK cell invasion against fetus trophoblast cells. The aim of this study was to evaluate the percentages of uNK cells and HLA-G1 and HLA-G5 isoforms expression in vaginal discharge of threatened-abortion women in comparison with control. In a case-control study, we investigated 30 threatened-abortion women with bleeding or spotting less than 20 weeks of pregnancy as compared to 30 normal pregnant women. uNK cells percentage was assessed by flow cytometry. Furthermore, we evaluated HLA-G1 and HLA-G5 isoforms expression by Real-Time PCR in these groups. The results of this study showed that threatened-abortion women had increased uNK cells and decreased T cells percentage in vaginal discharge in comparison with normal pregnant women (p=0.01, p=0.003, resp.). In addition, HLA-G1 isoform had lower expression in threatened-abortion women in comparison with control group p=0.0001. The increase of uNK cells level with the decrease of HLA-G expression in vaginal discharge of threatened-abortion pregnant women is an indicator of mother’s immune dysregulation. It is concluded that HLA-G expression level with uNK cells percentage can be determined as a diagnostic marker for threatened-abortion women.