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Rozita Jalalian,1 Tahereh Shokohi,2,3 Roghayeh Mirzakhani,4 Roya Ghasemian,5 Mohammad Taghi Hedayati,2,3 Sirus Ardalani,6 Soheil Azizi,7 Shamsi Kalhori,7 Firoozeh Kermani,4 Sabah Mayahi3 1Department of Cardiology, Mazandaran University of Medical Sciences, Sari, Iran; 2Invasive Fungi Research Centre (IFRC), Mazandaran University of Medical Sciences, Sari, Iran; 3Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; 4Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; 5Antimicrobial Resistance Research Center, and Department of Infectious Diseases, Mazandaran University of Medical Sciences, Sari, Iran; 6Department of Cardiac Surgery, Cardiovascular Research Center of Mazandaran Heart Center, Mazandaran University of Medical Sciences, Sari, Iran; 7Department of Pathology, Mazandaran Heart Center, Mazandaran University of Medical Sciences, Sari, IranCorrespondence: Tahereh ShokohiDepartment of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranTel +98 11 3354-3087Fax +98 11 3354-3248Email Shokohi.tahereh@gmail.comAbstract: Aspergillus endocarditis (AE) accounts for a-quarter of all fungal endocarditis, mainly in immunocompromised hosts prior to heart-valve surgery with high mortality, even with treatment. Herein, we report a rare case of AE in a diabetic 60-year-old woman with a history of redo mitral valve prosthesis suspecious of acute endocarditis. She underwent second redo surgical mitral valve replacement in combination with mechanical aortic valve replacement. Blood cultures were negative. The explanted valve and vegetation were subjected to identification. Grown colonies were identified as Aspergillus flavus, based on conventional and molecular methods. Despite the administration of liposomal amphotericin B and improvement in her general condition shortly after initiation of therapy, the patient passed away. As AE is a late consequence of redo prosthetic valve replacement, extended follow-up, early diagnosis, repeating valve-replacement surgeries, and timely selective antifungal treatments are warranted.Keywords: fungal endocarditis, Aspergillus, antifungal, prosthetic valve replacement

Background. Measuring the serum and alveolar procalcitonin level as inflammatory marker in the diagnosis of ventilator-associated pneumonia (VAP) has been taken into account. In this study, serum and alveolar procalcitonin levels in patients with suspected VAP and patients with confirmed VAP were compared.

The declining incidence of hepatitis A virus (HAV) infection in the Islamic Republic of Iran may be reducing the population's natural immunity. This was the first systemized, population-based survey of the seroprevalence of HAV antibodies in urban and rural inhabitants of Sari, Mazandaran province. Serum from 1034 individuals aged 1-25 years in 2007 were tested for anti-HAV IgG antibody using a commercial enzyme immunoassay kit. The overall seroprevalence was 38.9%. The lowest prevalence (5.2%) was among the younger age group (1-5 years) from urban areas and the highest prevalence (82.0%) in the older age group (15-25 years) from rural areas. Seropositivity was significantly higher at higher age, among females and in rural areas. Sari is no longer classified as an area of high endemicity, and immunization against HAV may be needed in our population in the future. [ABSTRACT FROM AUTHOR]

Introduction. Staphylococcus aureus is currently the most common cause of infection in hospitalized patients. Patients on hemodialysis are at increased risk due to their immunocompromised state. The present study was designed to determine the frequency of S aureus nasal carriage in patients on hemodialysis. Materials and Methods. This study was undertaken in 2 dialysis centers to establish the frequency of S aureus nasal carriage at teaching hospitals of Mazandaran University of Medical Sciences, in the north of Iran. Standardized nose swabs were rotated into the anterior nares of the patients, and the samples were cultured on a blood-agar medium. Having grown the colony, gram stain, catalase, manitol, DNAase, and coagulase tests were all performed. Pattern of antibacterial sensitivity was determined by using the disc diffusion method. Also, agar dilution method was used to determine minimal inhibitory concentration of oxacillin and vancomycin. Results. Of 84 patients on hemodialysis, 31 (36.9%) were nasal carriers of S aureus, of whom 23 (74.2%) were resistant to methicillin. Of the methicillin-resistant S aureus isolates, 3 (13.0%) were resistant to vancomycin and 7 (56.5%) had reduced susceptibility to vancomycin in agar dilution method. Resistance frequencies to clindamycin, ciprofloxacin, and trimethoprim-sulfamethoxsazole were 12.9%, 9.7%, and 19.3%, respectively. However, all microorganisms were sensitive to rifampicin. Conclusions. Patients on hemodialysis are at an increased risk of S aureus infections; thus, screening of these susceptible patients should be considered as a health priority. Meanwhile, microbial sensitivity tests should be ordered for all cases in order to optimize treatment options. [ABSTRACT FROM AUTHOR]

Background: Animal bites are potentially harmful for people. The prophylaxis approach is effective and safe, however, it is expensive and sometimes may be used without clear indication. Prophylaxis programs depend on local epidemiology. The aim of this study was to survey the animal bites and rabies epidemiology in northern Iran. Patients and methods: We performed a descriptive study on all animal bites and rabies in the Mazandaran Province during 2001 to 2005. Initial data including age, sex, site of bite, incidence, type of animal, geographical distribution, number of vaccinations and death by rabies were gathered and analyzed by SPSS soft ware. Results: Annual frequency of animal bites was between 3,174 and 4,670 in the Mazandaran Province. One hundred sixty bites per 100,000 persons occur annually, with a cost of approximately US $0.5 million in health care expenditures and loss of income. Twenty thousand animal bites occurred during the year or200l to 2005. Behshar, with 302.88 cases per 100,000 persons was the most prevalent city. We found that the majority ofbites are from dogs (84.87%), especially stray dogs. Men are frequently bitten by dogs (79.62%), while adolescence is the most frequent victims of dog bites, especially in rural areas. Dog bites resulted in 2 deaths, both of which had bites on their faces. Conclusion: Exposure to dogs, especially stray dogs in Mazandaran Province, reported the majority of cases of human bites and post-exposure prophylaxis. [ABSTRACT FROM AUTHOR]

Background: The annual risk of tuberculosis (TB) in Iran is about 0.5% with annual incidence rate of 23/100000 (16322 cases). Different factors have been postulated as TB predisposing factors. Several studies have linked smoking with pulmonary tuberculosis as the TB incidence in their adult men was 2.4 times higher than women. In Iran, however, this ratio is equal and somewhere the ratio in women is greater. We decided to carry out a case control study in order to evaluate the effect of cigarette smoking on pulmonary TB. Patients and methods: A case-control study was achieved in health care centers of Mazandaran province (affiliated to Mazandaran University of Medical Sciences). Participants were men aged 15 years and older who were enrolled in health care centers with the diagnosis of active pulmonary tuberculosis. One hundred men (aged 15-85 years) with bacteriological TB (smear or culture positive) were selected as cases and 300 age-matched men without TB were selected randomly as controls. Information on smoking status, quality of tobacco smoked and duration of cigarette smoking and also the age at which smoking was first commenced were collected by a questionnaire. Results: Smokers were 2.1 times more likely to develop pulmonary TB (OR=2.10, 95% confidence interval (CI):1.33- 2.33, p<0.04). The age adjusted odds ratio was 1.804 (95%CI:1.66-2.5, p<0.05). Quantity of cigarette smoking and duration of smoking had positive association with pulmonary TB. The ORs for mild (1-10 cigarette/day), moderate (11- 20/day) and heavy (>20/day) smoking were 1.68, 2.46, and 2.56, respectively (p<0.05). The ORs for duration of smoking with <10 years, 11-20 years and >20 years of smoking were 0.91, 2.48, and 2.9, respectively (p< 0.001). Conclusion: We conclude that smoking may increase the risk of pulmonary TB in men. Further studies should be conducted to investigate this association and to establish whether smoking reduction strategies contribute to tuberculosis control. [ABSTRACT FROM AUTHOR]

Objective: Escherichia coli is the most important etiologic factor in urinary tract infection (UTI), which is becoming resistant to the common antibiotics. The aim of this study was to evaluate the resistance of this bacterium to the antibiotics that are commonly used. Materials and Methods: A descriptive study conducted in patients with uncomplicated UTI referring to Sari hospitals during 2013-2014. For this purpose, samples that had positive urine culture were selected and evaluated with antibiogram. In addition, E-Test MIC method was used for antibiotics ciprofloxacin and co-trimoxazole. SPSS software was used for data analysis. Results: Of the 101 patients studied, 83 (82.2%) were females and 18 (17.8%) were male. The mean age of patients was 40.32 ± 3.22 years. The most sensitivity was seen to nitrofurantoin (92.07%), gentamicin (76.23%). Most resistance was also seen to the antibiotics amoxicillin (74.25%), co-trimoxazole (64.35%) and ciprofloxacin (36.63%). In E-Test MIC method, 23.7% were resistant to the ciprofloxacin and 43.5% to co-trimoxazole. Conclusion: Due to the high antibiotic resistance that was observed to ciprofloxacin and co-trimoxazole in this study, it seems a better alternative antibiotic such as nitrofurantoin should be used for the empirical treatment of patients with UTIs.

Background and Objectives: This study aimed to investigate the possible prognostic significance of interferon alpha-beta receptor subunit 2 (IFNAR2) and tyrosine kinase 2 (TYK2) expressions., Methods: We conducted a retrospective study including COVID-19 adult patients. All blood samples were collected before any interventions. The expressions of IFNAR2 and TYK2 were assessed using real-time PCR in venous blood samples of 54 cases and 56 controls. The transcript quantities of IFNAR2 and TYK2 genes were assessed using a Delta-Ct method., Results: Our findings show no significant differences in gene expression levels for IFNAR2 and TYK2 between patients who required oxygen (O2) therapy and those who did not (p-value = 0.732 and p-value = 0.629, respectively). Likewise, there were no significant differences in IFNAR2 and TYK2 expressions between patients hospitalized for less than 7 days and those hospitalized for 7 days or more (p-value = 0.455 and p-value = 0.626, respectively). We also observed a weak correlation between IFNAR2 expression and CRP (p-value = 0.045, r = 0.192). There was a negative correlation between the expression levels of IFNAR2 and TYK2 transcripts in COVID-19 patients (p-value = 0.044; partial correlation coefficient = -0.283). Additionally, IFNAR2 and TYK2 were significantly downregulated in the COVID-19 group compared to healthy subjects (p-value = 0.002 and p-value = 0.028, respectively). However, neither IFNAR2 nor TYK2 expression was significantly different between the case subgroups based on COVID-19 severity. The IFNAR2 ΔΔCt (B = -0.184, 95% CI: -0.524-0.157, p-value = 0.275) and the TYK2 ΔΔCt (B = 0.114, 95% CI: -0.268-0.496, p-value = 0.543) were not found to be significant predictors of hospitalization duration. The area under the curve (AUC) for IFNAR2 expression is 0.655 (p-value = 0.005, 95% CI: 0.554-0.757), suggesting its poor discriminative value., Conclusion: We were unable to comment definitively on the prognostic power of IFNAR2 and TYK2 expressions in COVID-19 patients, and larger-scale studies are needed. The principal limitations of this study included the lack of longitudinal analysis and limited sample size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Razavi, Raei, Hatami, Chokami, Goudarzi, Ghasemian, Alizadeh-Navaei, Yarmohammadi, Soltanipur, Tabarestani, Valadan, Meshkinfam Haghighi, Tarsi and Razavi.)

The use of nanotechnology products with supermagnetic properties for targeted delivery of drugs has gained attention recently. Due to the anticancer features of Gingerol, the major phenolic compound from Ginger, this study aims to prepare Fe 3 O 4 @Glucose-Gingerol nanoparticles (NPs) and investigate their anticancer potential in a lung adenocarcinoma cell line. The physical and chemical features of the nanoparticles were investigated by FT-IR, XRD, zeta potential, DLS, EDS mapping, VSM, and electron microscope imaging. Cytotoxic effects of the nanoparticles for the A549 (lung adenocarcinoma) and MRC-5 (normal) cell lines was investigated by MTT assay. Furthermore, the effects of Fe 3 O 4 @Glucose-Gingerol nanoparticles on the expression of the CASP8 , BAX , and BCL2 genes and the activity of Caspase 3 were characterized. The flow cytometry assay (annexin V/PI) was employed to find out the percentage of apoptotic cells. The Fe 3 O 4 @Glu-Gingerol NPs were spherical (42-67 nm), without elemental impurity, and with surface charge, DLS size, and magnetic saturation of -47.7 mV, 154 nm, and 35 emu/g, respectively. Fe 3 O 4 @Glu-Gingerol NPs showed a remarkable greater toxicity in the A549 cells than normal cell line with the 50 % inhibition concentration (IC 50 ) of 190 and 554 μg/mL, respectively. Treatment of lung adenocarcinoma cells with the Fe 3 O 4 @Glu-Gingerol NPs led to an increase in cell apoptosis from 4.6 to 39.48 %. Also, the CASP8 and BAX genes were upregulated by 2.49 and 2.8 folds, respectively, while a downregulation by 0.75 folds was noticed for the BCL2 . Moreover, apoptotic features were observed in Fe 3 O 4 @Glu-Gingerol NPs treated cells by Hoechst staining, and activation of Caspase 3 by 2.8 folds. This study revealed that the Fe 3 O 4 @Glu-Gingerol NPs have antiproliferative effects on the lung adenocarcinoma cell line by activation of intrinsic and extrinsic apoptosis that is a promising feature in cancer treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Introduction: Selective serotonin reuptake inhibitors are considered the drugs, whose effectiveness in viral pandemics has been studied. The aim of this study was to evaluate of adding fluoxetine to the treatment regimen of patients with COVID-19 pneumonia., Methods: This study was a double-blind randomized placebo controlled clinical trial .36 patients in the fluoxetine and 36 patients in the placebo group were enrolled. Patients in the intervention group were first treated with fluoxetine 10 mg for 4 days and then the dose of 20 mg was continued for 4 weeks. Data analysis was conducted using SPSS V. 22.0., Results: There was no statistically significant difference between the two groups in terms of clinical symptoms at the beginning of the study and also the score of anxiety and depression, oxygen saturation at the time of hospitalization, mid-hospitalization and discharge periods. The need for mechanical ventilator support (p = 1.00), the need for admission in the intensive care unit (ICU) (p = 1.00), rate for mortality (p = 1.00), and discharge with relative recovery (p = 1.00) were not significantly different between the two groups. The distribution of CRP within the study groups showed a significant decrease during different time periods (p = 0.001), and although there was no statistically significant difference between the two groups on the first day (p = 1.00) and at discharge (p = 0.585), mid-hospital CRP showed a significant decrease in the fluoxetine group (p = 0.032)., Conclusion: Fluoxetine resulted in a faster reduction of patients' inflammation without association with depression and anxiety., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10 mL of phage suspension every 12 h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of O 2 Sat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of O 2 Sat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value < 0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background and Aim: Delirium has been presented as the leading cause of sudden change in the mental state of patients with coronavirus disease 2019 (COVID-19). Given that the delayed diagnosis of such a dysfunction is often associated with excess mortality, it seems essential to devote vastly more attention to this significant clinical characteristic., Materials and Methods: This cross-sectional study was performed on 309 patients [viz. 259 cases hospitalized in general wards and 50 individuals admitted to the intensive care unit (ICU)]. For this purpose, a Demographic-Clinical Information Questionnaire, the Confusion Assessment Method (CAM), the Confusion Assessment Method for the ICU (CAM-ICU), the Richmond Agitation-Sedation Scale (RASS) and face-to-face interviews were completed by a trained senior psychiatry resident. The data analysis was further done with the SPSS Statistics V22.0 software package., Results: Out of 259 patients admitted to the general wards and 50 cases in the ICU due to COVID-19, 41 (15.8%) and 11 (22%) individuals were diagnosed with delirium, respectively. As well, a significant relationship was observed between the incidence rate of delirium and age (p < 0.001), level of education (p < 0.001), hypertension (HTN) (p = 0.029), a history of stroke (p = 0.025), a history of ischemic heart disease (IHD) (p = 0.007), a history of psychiatric disorders, a history of cognitive impairment (p < 0.001), use of hypnotic and antipsychotic medications (p < 0.001) and a history of substance abuse (p = 0.023). Among 52 patients with delirium, only 20 cases had received psychiatric consultation by consultation-liaison psychiatry service for the possibility of delirium., Conclusion: In view of the high frequency of delirium among COVID-19 inpatients, their screening for this important mental state should be a priority in clinical settings., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown., Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults., Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021., Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection., Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed., Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths., Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price., Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness., Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 ( IFI27 ) in COVID-19 patients., Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27- like genes were highly upregulated in the blood samples of severely infected patients., Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus., Competing Interests: FS-F-G is a consultant for Biotheus Inc. KS is a consultant for Sanofi, Roche and NovoNordisk. The opinions and data presented in this manuscript are of the authors and are independent of these relationships. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shojaei, Shamshirian, Monkman, Grice, Tran, Tan, Teo, Rodrigues Rossi, McCulloch, Nalos, Raei, Razavi, Ghasemian, Gheibi, Roozbeh, Sly, Spann, Chew, Zhu, Xia, Wells, Senegaglia, Kuniyoshi, Franck, dos Santos, Noronha, Motamen, Valadan, Amjadi, Gogna, Madan, Alizadeh-Navaei, Lamperti, Zuñiga, Nova-Lamperti, Labarca, Knippenberg, Herwanto, Wang, Phu, Chew, Kwan, Kim, Teoh, Pelaia, Kuan, Jee, Iredell, O’Byrne, Fraser, Davis, Belz, Warkiani, Gallo, Souza-Fonseca-Guimaraes, Nguyen, Mclean, Kulasinghe, Short and Tang.)

Due to the high prevalence and considerable increase of prostate cancer, finding novel therapeutic compounds for the treatment of prostatic cancer has been the goal of many researches. In this study, we aimed to fabricate the Bismuth oxide (Bi 2 O 3 ) NPs, functionalized with glutamine (Gln) and conjugated with Thiosemicarbazide (TSC). Then, the anticancer mechanism of the synthesized NPs was investigated using the cellular and molecular tests including MTT assay, Flow cytometry, Caspase-3 activity assay, Hoechst staining and Real Time PCR. The FT-IR and XRD assays confirmed the identity of the synthesized Bi 2 O 3 /Gln-TSC NPs. The size range of the synthesized spherical particles was 10-60 nm and the zeta potential was - 23.8 mV. The purity of the NPs was confirmed by EDX-mapping analysis. The Bi 2 O 3 /Gln-TSC was considerably more toxic for prostate cancer cells than normal human cells and the IC 50 was calculated 35.4 and 305 µg/mL, respectively. The exposure to the NPs significantly increased the frequency of apoptotic cells from 4.7 to 75.3%. Moreover, the expression of the CASP8, BAX, and Bcl-2 genes after exposure to the NPs increased by 2.8, 2.3, and 1.39 folds. Treating the cancer cells with Bi 2 O 3 /Gln-TSC increased the activity of the Caspase-3 protein and apoptotic morphological features were observed by Hoechst staining in the treated cells. This work showed that Bi 2 O 3 /Gln-TSC has considerable cytotoxicity for prostate cancer cells and could inducing both intrinsic and extrinsic pathways of apoptosis., (© 2022. The Author(s).)

Background: Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed., Methods: We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days., Results: Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04-1.66]; p -value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15-1.45]; p -value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever ( p -value = 0.040), cough ( p -value = 0.019), and weakness ( p -value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65-2.84]; p -value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60-1.09]; p -value = 0.16)., Conclusion: Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19., Clinical Trial Registration: www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rezai, Ahangarkani, Hill, Ellis, Mirchandani, Davoudi, Eslami, Roozbeh, Babamahmoodi, Rouhani, Alikhani, Najafi, Ghasemian, Mehravaran, Hajialibeig, Navaeifar, Shahbaznejad, Rahimzadeh, Saeedi, Alizadeh-Navai, Moosazadeh, Saeedi, Razavi-Amoli, Rezai, Rostami-Maskopaee, Hosseinzadeh, Movahedi, Markowitz and Valadan.)

Background and Aim: Health care workers (HCWs), mostly frontliners, are encountering numerous physical and psychosocial stressors, and even managing some conflicts over the course of the novel coronavirus disease 2019 (COVID-19). In this respect, the present study was to investigate the prevalence rate of occupational burnout (OB) in such workers during this pandemic., Materials and Methods: This cross-sectional study was conducted between April 6 and May 30, 2020, via an online survey in 31 provinces of Iran, on HCWs selected based on convenience sampling method. For data collection, a socio-demographic information form and the Maslach Burnout Inventory (MBI) was utilized. Descriptive statistics, Chi-square test, and multivariate regression analysis were also applied to test the research hypotheses., Results: In total, 7626 HCWs participated in the present study. Accordingly, 73.2 and 26.8% of the workers were female and male, respectively. As well, 57.8% of the respondents were nurses and 14.4% of the cases were clinicians. Moreover, 44.8% of the participants had thus far worked in isolation wards and 40.3% of these individuals reported working for 4-8 hours with COVID-19 patients. The prevalence rate of OB was 18.3%. Besides, 34.2, 48.7, and 56.1% of the respondents had severe levels of emotional exhaustion (EE), higher depersonalization (DP), and decreased sense of personal accomplishment (PA), respectively. Besides, the HCWs at the age range of 20 to 30, having female gender, no children, and a bachelor's degree, and working in isolation wards showed the higher levels of OB with reference to the Chi-square test results (p < 0.001). Accordingly, the statistical test outcomes demonstrated that a history of physical illnesses (p = 0.001) and psychiatric disorders (p = 0.044) could be the best predictor of OB throughout the first peak of the COVID-19 pandemic., Conclusion: Regarding the high prevalence rate of OB among the HCWs and the remaining COVID-19 journey in Iran, health care managers are recommended to orient the required management and coping strategies toward improving mental health in these individuals., (© 2022. The Author(s).)

Since numerous studies have stated that there may be a relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease, and because of the high prevalence of both conditions worldwide, this study investigated the risk of non-alcoholic fatty liver disease in patients infected with H. pylori. Following a systematic review of PubMed, Scopus, Web of Science and Embase, and a search in Google Scholar using MeSH terms such as H. pylori and non-alcoholic fatty liver disease, the relevant papers up to November 2020 were reviewed. All cohort, case-control, and cross-sectional studies that examined the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori entered this study. A meta-analysis was conducted in STATA 11. This systematic review examined 22 papers with 117 117 participants (33 711 patients infected with H. pylori and 83 406 participants as control) and 20 studies were subjected to meta-analysis The results indicated a 22% to 27% increase in the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori (crude odds ratio: 1.27, 95% CI: 1.17-1.33; and adjusted odds ratio: 1.22, 95% CI: 1.09-1.35). According to the subgroup analysis, the study region, sample size, and the method of diagnosing H. pylori were the factors contributing to the high heterogeneity. The meta-analysis revealed the increased risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori. This indicates that H. pylori is a serious risk factor in patients susceptible to NAFLD.

Background: Evaluation of protease inhibitors (PIs) is important in terms of prescribing an effective regimen for reducing mortality and hospitalization in Covid-19. Therefore, follow-up of patients better determines the characteristics of existing regimens., Methods: We retrospectively evaluated the demographic, co-morbidities, gastrointestinal (GI) and liver complications of patients at two teaching hospitals from the first of March to the end of July 2020. All patients received one of two recommended regimens including hydroxychloroquine (HCQ) (400 mg BD on the first day and then 200 mg BD) plus atazanavir/ritonavir (ATV) (300/100 mg daily) or HCQ with the same dose plus lopinavir/ritonavir (Kaletra) (400/100 mg BD) for 5-7 days., Results: We chose 170 cases that received 2 different regimens. In group one, 85(57.6% males) patients received Kaletra and HCQ and group two, 85 (55.3% males) patients received ATV and HCQ. The study of hospitalization in both groups showed no difference in more or less than 5 days hospitalization. (P=0.757) Comparison of mortality rates has not shown a significant difference including 19 (22.4%) deaths in group 1 and 15(17.6%) deaths in group 2 (P=0.443). Nausea followed by diarrhea was the most common side effects in group 1. But no side effects were reported in group 2 (P=0.000). Abnormal liver function tests (LFTs) were seen in both groups., Conclusion: Comparison of hospitalization and mortality were not statistically significant. It seems that a respect to similar effect on mortality and hospitalization. ATV regimen is superior to Kaletra especially for better GI tolerance and less daily pills., Competing Interests: There is no conflict of interests of any of the authors.

Aim: The main purpose of this study was to assess the levels of anxiety, depression, and stress among healthcare providers in Iran., Methods: This descriptive cross-sectional survey was performed on healthcare providers selected through the convenience sampling method from April 6 to May 19, 2020, during the COVID-19 pandemic. To this end, a self-report web-based questionnaire made up of a sociodemographic characteristics information form, Depression, Anxiety, and Stress Scale (DASS), and Corona Disease Anxiety Scale (CDAS) was distributed. Descriptive statistics, chi-square test (χ 2 ), and univariate and multivariate logistic regression models were accordingly practiced to analyze the data using the Statistical Package for Social Sciences (SPSS) software., Results: Of 1343 healthcare providers, 45.8% and 73.0% had moderate physical and psychological anxiety symptoms, respectively. The logistic regression model similarly demonstrated that anxiety caused by COVID-19 was significantly correlated with the age ranges of 41-50 (P = .007) and 51-60 (P = .014) years as well as male participants (P < .001). In addition, the prevalence rates of depression and stress were, respectively, reported by 35.1% and 27.8%. There was correspondingly a significant relationship between depression and age as well as stress and gender., Conclusions: It seems that healthcare managers need to focus more attention on psychological aspects in healthcare providers during this pandemic and plan to teach them about coping strategies., (© 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of Neuropsychopharmacology.)

Background: The cause of coronavirus disease 2019 (COVID-19) is a virus which can lead to severe acute respiratory syndrome-CoV-2 (SARS-COV-2). There are evidences of involvement of immune system in pathogenesis of this disease. We investigated the presence of various vasculitis-associated autoantibodies and complement levels in patients with COVID-19., Materials and Methods: Patients with severe or critical type of COVID-19 were evaluated for symptoms, signs, and laboratory tests of vasculitis syndromes including rheumatoid factor (RF), antinuclear antibody (ANA), anti-double-stranded DNA, c and p anti-neutrophilic cytoplasmic antibody (c ANCA and P ANCA), and complement levels., Results: The study was performed in forty patients with severe or critical illness. The mean age of the participants was 48.5 ± 9.8 years. All patients had pulmonary involvement in lung computed tomography scans. Vasculitis laboratory test results included RF in two patients, ANA in three patients, and ANCA in one patient. Seventeen (42.5%) patients had hypocomplementemia in one or more complement tests. Four patients expired, of whom three had a decrease in complement level., Conclusion: Decrease in complement levels may predict a critical state of COVID-19 disease. Therefore, measuring its levels may be of great benefit in making earlier decisions to initiate disease-suppressing treatments including corticosteroids., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Research in Medical Sciences.)

Objectives: The present study was conducted to assess 3(HCWs) during the COVID-19 pandemic., Methods: A total number of 7626 HCWs were included in this web-based cross-sectional study, via the convenience sampling technique. To collect the required data, the sociodemographic characteristics information form, the Depression Anxiety Stress Scale-21 (DASS-21), and the Corona Disease Anxiety Scale (CDAS) were also employed. In addition, data analysis was performed using the SPSS Statistics software (ver. 24), as well as descriptive statistics, Chi-square test (χ 2 ), and univariate/multivariate logistic regression models., Results: The CDAS results revealed that 47.9% and 70.5% of the HCWs had experienced moderate levels of physical and psychological anxiety, respectively. Based on the DASS results, 44.8%, 43%, and 34.8% of the HCWs had been subjected to depression, anxiety, and stress symptoms during the COVID-19 pandemic, respectively. The logistic regression models correspondingly showed that depression among the HCWs was significantly correlated with risk factors, such as the age groups of 20-30 years (p = .001), 31-40 years (p = .006), female HCWs (p> .001), history of physical illnesses (p = .004), and history of psychiatric disorders (p> .001). Moreover, factors including the age groups of 20-30 years (p < .001), 31-40 years (p < .001), 41-50 years (p < .001), female HCWs (p> .001), history of physical illnesses (p < .001), and history of psychiatric disorders (p>.001) were assumed as significant predictors of anxiety in these individuals. Besides, factors such as the age groups of 20-30 years (p = .002), 31-40 years (p = .004), female HCWs (p>.001), occupation (p = .016), history of physical illnesses (p < .001), and history of psychiatric disorders (p> .001) could significantly predict the prevalence rate of stress in the HCWs in times of this crisis., Conclusion: Given the importance of mental health status among HCWs during the COVID-19 pandemic, health administrators and policymakers of the Ministry of Health and Medical Education in Iran are suggested to provide psychological screening and supportive care programs for HCWs with the aim of enhancing their mental health and successful coping with critical circumstances., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

A novel member of human coronavirus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been recently recognized in China and rapidly spread worldwide. Studies showed the decreasing of peripheral blood lymphocytes in a majority of patients. In this study, we have reported the clinical features, laboratory characteristics, the frequency of peripheral blood lymphocyte subpopulations, and their apoptosis pattern in Iranian coronavirus infectious disease (COVID-19) patients. Demographic and clinical data of 61 hospitalized confirmed cases with COVID-19 at Imam Khomeini Hospital were collected and analyzed. Peripheral blood mononuclear cells were isolated from all samples and the apoptosis pattern was evaluated using Annexin V/propidium iodide method. The frequency of lymphocyte subsets, including T-CD4 + , T-CD8 + , NK, B cells, and monocytes, was measured in all patients and 31 controls by flow cytometry. Our findings demonstrated that the percentage of lymphocytes, CD4 + , and CD8 + T cells were decreased in COVID-19 patients compared with the control group. Regarding the clinical severity, the number of lymphocytes, CD4 + , CD8 + T cells, and NK cells were also decreased in severe cases when compared with mild cases. Finally, our data have also indicated the increase in apoptosis of mononuclear cells from COVID-19 patients which was more remarkable in severe clinical cases. The frequency of immune cells is a useful indicator for prediction of severity and prognosis of COVID-19 patients. These results could help to explain the immunopathogenesis of SARS-CoV-2 and introducing novel biomarkers, therapeutic strategies, and vaccine candidates., (© 2020 Wiley Periodicals LLC.)

Background: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). ; Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard-dose group, 13 patients) as a 3h infusion. The primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. Sputum culture was taken before the intervention. ; Results: Clinical success rate was not significantly different between the high and standard-dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in the reduction of clinical pulmonary infection score (CPIS) compared to a high dose to the standard group (P=0.038). SOFA score declined significantly in the high dose group throughout the study (P=0.006). A shorter duration of VAP treatment was recorded in the high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures. ; Conclusion: Treatment with the high dose of meropenem seems to be safe. However, it did not provide a significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reduction in SOFA and CPIS. ; The trial protocol was registered with IRCT.ir (registration number IRCT2010010700 3014N19 in April 2018)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Metallo-β-lactamases (MBLs) play a major role in the resistance of Pseudomonas aeruginosa to carbapenems. We investigated the antibiotic susceptibility patterns and frequency of MBLs genes (bla IMP and bla SPM ) in carbapenem-resistant P. aeruginosa clinical isolates in Sari, Iran., Materials and Methods: The isolates were identified using standard microbiological tests, and their antibiotic susceptibility pattern was determined by the disk agar diffusion method according CLSI criteria. Phenotypic identification of MBL-producing strains assessed by the combined disk test (CDT). Then, polymerase chain reaction (PCR) was used to detect the presence of bla IMP and bla SPM genes., Results: The highest and lowest levels of antibiotic resistance were observed against gentamicin (40%) and piperacillin-tazobactam (13%), respectively. Besides, 40 isolates (40%) had the multi-drug resistant (MDR) phenotype, while 5 (12.5%) MDR isolates were resistant to all antibiotics tested. The results of the CDT showed that among 43 carbapenem non-susceptible clinical isolates of P. aeruginosa, 33 (76.74%) isolates were MBL-producing strains. Also, the frequency of the bla IMP gene among 43 carbapenem non susceptible isolates was determined to be 6.97%, while none of these isolates carried the bla SPM gene., Conclusion: Due to the high prevalence of carbapenem-resistant and MDR P. aeruginosa in this study, routine antibiotic susceptibility testing and phenotypic identification of carbapenemase production by this bacterium are necessary for the proper selection of antibiotics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Due to the emergence of the new coronavirus 2019 and the lack of sufficient information about infected patients, this study was conducted to investigate the chest high-resolution computed tomography (HRCT) findings of patients infected with the new coronavirus 2019., Methods: This cross-sectional study was performed on COVID-19 patients referred to Medical Imaging Centers of Sari, Mazandaran, Iran, on March 2020 for computed tomography (CT) scan. Symptomatic patients were referred to the Medical Imaging Center for diagnosis confirmation through CT scan. In addition to age and sex, HRCT findings were collected from the picture archiving and communication system (PACS) for further evaluations., Results: Out of 552 patients with mean age of 51.2 ± 14.8 years, the male/female ratio was 1.38 to 1. The most common expressive findings in patients were ground-glass opacity (GGO) (87.3%), peripheral distribution (82.4%), and posterior distribution (81.5%). The most conflicting findings in patients were pleural effusion (7.6%), peribronchovascular distribution (7.6%), and lymphadenopathy (5.1%). The peripheral distribution (p = 0.034), round opacities (p = 0.02), single lobe (p = 0.003), and pleural effusion (p = 0.037) were significant in people under and over 50 years of age., Conclusion: In summary, the present study indicated that in addition to GGO, peripheral distribution findings could be a vital diagnostic choice in COVID-19 patients.