High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial.

Objective: In the COVID-19 pandemic, the SARS-CoV-2 virus has infected millions of people worldwide. Mortality primarily results from the inflammation state and its complications. High-dose melatonin has been established as an anti-inflammatory agent. This study evaluated high-dose melatonin as an adjuvant therapy in critically ill patients with SARS-CoV-2 infection. Methods: We conducted a double-blinded, randomized clinical trial of 21 mg of melatonin per day compared with a placebo in 67 patients with COVID-19. We enrolled patients older than 18 years of age with documented SARS-CoV-2 infection, who were admitted to the intensive care unit and underwent invasive mechanical ventilation. Administration of melatonin and placebo through a nasogastric tube continued for 5 days. The main outcomes were mortality rate, duration of mechanical ventilation, changes in oxygenation indices, and C-reactive protein (CRP) levels. Results: No significant differences were observed in mortality and duration of mechanical ventilation between the control and intervention groups. After 5 days of the intervention, the mean (±standard deviation) CRP and platelet count were 47.28 (±38.86) mg/L and 195.73 (±87.13) × 1000/µL, respectively, in the intervention group and 75.52 (±48.02) mg/L and 149.62 (±68.03) × 1000/µL, respectively, in the control group (P < 0.05). Conclusion: High-dose melatonin in intubated patients with COVID-19 was associated with a decrease in CRP levels. However, this treatment did not apparently affect patient outcomes.

Management of a critically ill patient with COVID-19-related fulminant myocarditis: A case report.

A 78-year-old man with COVID-19 infection was admitted. Initial echocardiography indicated left ventricular ejection fraction (LVEF) of 15%, high pulmonary arterial pressure, severe left ventricular dysfunction, mild diastolic dysfunction, mild regurgitation mitral valve, and normal septal thickness. Considering the probable diagnosis of COVID-19-related myocarditis, the patient was early managed with the antivirals, immunomodulatory agents, a high dose of ascorbic acid, melatonin, and immunoglobulin therapy. His clinical condition was improved and his last echocardiography revealed LVEF of 40% and improvement in systolic and diastolic dysfunction. The clinicians should be aware of the potentially lethal cardiac complication of COVID-19, especially in geriatrics.

The effect of educational intervention based on the self-efficacy theory of high school students in adopting preventive behaviors of COVID-19.

BACKGROUND: The COVID-19 pandemic has become a major problem for education systems. This study was conducted to investigate the effect of educational intervention based on the self-efficacy theory of high-school students in adopting preventive behaviors of COVID-19. MATERIAL AND METHODS: This quasi-experimental study was performed on Hazrat Zahra and Shahed high-school students in Jahrom (southern Iran) in 2021. In total, 160 students (80 each in the intervention group and the control group) were selected by multistage random sampling. Data collection tools included a demographic information questionnaire and self-efficacy in adopting preventive behaviors from COVID-19 researcher-made questionnaire. Questionnaires were completed by all participants before and 3 months after the educational intervention. The educational intervention was performed for 6 weeks by using an educational program based on Bandura self-efficacy theory. The intervention was performed during 12 sessions of face-to-face training in the classroom (two 1-h sessions per week), distributing educational packages and sending educational videos through cyberspace. Data were analyzed using Chi-square test, independent t test, paired t test, and linear regression. RESULTS: After the educational intervention, a significant difference was observed in the intervention group before and after the educational intervention (P = 0.018) and between the intervention and the control groups (P = 0.001) in the self-efficacy in adopting preventive behaviors from COVID-19 score. Also, the average self-efficacy score of students increased with an increase in parental education level and a history of COVID-19 in family members. CONCLUSION: Educational intervention based on self-efficacy theory was shown as an effective method to improve students' self-efficacy in adopting preventive behaviors from COVID-19.

Preoperative platelet distribution width-to-platelet count ratio as a prognostic factor in patients with glioblastoma multiforme.

BACKGROUNDS: The prognostic significance of the platelet volume indices (PVIs), including the platelet distribution width (PDW), mean platelet volume (MPV), and platelet distribution width-to-platelet count ratio (PDW/P) has been demonstrated in a variety of malignancies. This study aimed to evaluate the prognostic value of PVIs in patients with a newly diagnosed glioblastoma multiforme (GBM). METHODS: We retrospectively evaluated the clinical data of 143 patients with GBM who managed at our center between May 2010 and May 2019. Receiver operating characteristic curves (ROC) for cutoff value determination, Kaplan-Meier survival analysis, and univariate and multivariate Cox regression analyses were performed. RESULTS: The corresponding cutoff values for MPV, PDW, and PDW/P were 9.05, 14.7, and 0.51, respectively. The Kaplan-Meier survival analyses showed that patients with an MPV < 9.05 and those with PDW <14.7 and cases with PDW/p < 0.51 had a longer overall survival (OS) (p < 0.05). Based on univariate analysis, age, Karnofsky Performance Status scores (KPS), tumor focality, MPV, PDW, and PDW/P were predictors of OS (p < 0.05). Final multivariate Cox regression analyses showed age (HR 1.040, 95% CI 1.009-1.071, P,0.011), KPS (HR 2.208, 95% CI 1.107-4.405, P,0.025), tumor focality (HR 4.596, 95% CI 1.988-10.626, p < 0.001), and PDW/P (HR 1.786, 95% CI 1.103-3.072, P,0.037) as the independent predictors of OS in patients with newly diagnosed glioblastoma. CONCLUSIONS: Our results suggest an elevated preoperative PDW/P, along with previously established variables, as a simple and inexpensive prognostic factor for patients with GBM.

Assessment of the Antibacterial Effects of Bismuth Nanoparticles against Enterococcus faecalis.

INTRODUCTION: Enterococcus faecalis (E. faecalis) is the most important species in dentistry and plays a significant role in the etiology of persistent apical lesions after root canal treatment. Up to date, the intracanal application of 2% chlorhexidine for 7 days is the best way to eliminate E. faecalis. However, due to the ability of this bacterium to persist and survive in harsh environments, many studies have been directed towards finding an alternative strategy for prevention or eradication of it. This study was conducted to investigate the effect of bismuth nanoparticles on E. faecalis, as an etiologic factor in recurrent root canal infections. METHODS: Forty patients, referred to Endodontic Ward of Shiraz University of Medical Science for endodontic pretreatment, provided root canal samples. First, all samples were transferred in Enterococcosel broth and incubated. Then, samples which showed growth were plated on blood agar plates and incubated for further PCR procedure. Nanoparticle powder was dissolved in high-purity water, and the final concentration of bismuth nanoparticles (BiNPs) was measured by the spectrophotometer. Minimum inhibitory concentration (MIC) of BiNPs against E. faecalis was determined by microbroth dilution method according to methods for antimicrobial susceptibility tests. Also, bactericidal assays were conducted in Mueller-Hinton broth medium and reported as the concentration of BiNPs that reduced the viable bacterial count by 99.9%. RESULTS: Of all samples, 77.5% revealed the presence of E. faecalis by PCR. Also, E. faecalis growth inhibition was observed at concentrations ranging from 0.625 µg/ml to 20 µg/ml (geometric mean: 2.337 µg/ml), and the MBC values were between 1.25 µg/ml and 40 µg/ml (geometric mean: 4.781 µg/ml), which in comparison with chlorhexidine, these values were about one-eighth of chlorhexidine. CONCLUSION: The experimental data suggest that bismuth nanoparticles could be an interesting alternative to combat E. faecalis, which, in view of the advantages mentioned for bismuth nanoparticle like inhibiting Streptococcus mutans biofilm formation and higher antibacterial activity compared to chlorhexidine, can be suggested to be used in different fields of dentistry.

Evaluation of Antibiotic Resistance Pattern in Dental Bacteremia Detected by Multiplex PCR Technique.

The aim of this study was to detect oral bacteremia and offer the antibiotic resistance patterns. Bacterial resistance pattern was evaluated in 50 patients. A spectrophotometer device equipped with UV and electrophoresis of the extracted samples on agarose gel for antibiogram test were used. PCR test 15 minutes after tooth extraction showed that bacterial strains were extracted from 16 patients. Lactobacillus, Enterococcus faecalis (E. faecalis), Streptococcus sanguinis (S. sanguinis), Streptococcus salivarius (S. salivarius), and Streptococcus mutans (S. mutans) were extracted from 5, 4, 4, 4, and 6 patients. 100% of Lactobacillus, E. faecalis, S. sanguinis, S. salivarius, and S. mutans were sensitive to tigecycline. Most of the Lactobacillus antibiotic resistance was against tetracycline and ciprofloxacin. Antibiotic resistance in S. salivarius was observed in 75% of the cases against piperacillin-tazobactam, ciprofloxacin, and cefotaxime, while in S. mutans was 84% of the cases against ceftriaxone. The results of the current study showed that tooth extraction causes bacteremia before, during, and after tooth extraction. Generally, the highest antibiotic resistance occurred against tetracycline, ciprofloxacin, and ampicillin-sulbactam. In most cases, the bacteria showed partial resistance to these antibiotics; however, tigecycline showed 100% efficacy on all types of bacteria. Streptococcus strains (salivarius, mutans, and sanguinis) were sensitive to most of the antibiotics while antibiotic sensitivity was less evident in Lactobacillus and E. faecalis. Antibiotic resistance has become a critical issue, since it leads to treatment failure when there is a need for antibiotic therapy.

Poly-phosphate increases SMC differentiation of mesenchymal stem cells on PLGA-polyurethane nanofibrous scaffold.

The use of bioactive scaffolds in tissue engineering has a significant effect on the damaged tissue healing by an increase in speed and quality of the process. Herein, electrospinning was applied to fabricate composite nanofibrous scaffolds by Poly lactic-co-glycolic acid (PLGA) and Polyurethane (PU) with and without poly-phosphate (poly-P). Scaffolds were characterized morphologically by scanning electron microscope (SEM), and their biocompatibility was also investigated by SEM, protein adsorption, cell attachment and survival assays. The applicability of the scaffolds for bladder tissue engineering was also evaluated by culturing mesenchymal stem cells (MSCs) on the scaffolds and their differentiation into smooth muscle cell (SMC) was studied at the gene and protein levels. The results demonstrated that scaffold biocompatibility was increased significantly by loading poly-P. SMC related gene and protein expression level in MSCs cultured on poly-P-loaded scaffold was also increased significantly compared to those cells cultured on empty scaffold. It can be concluded that poly-P hasn't also increased scaffold biocompatibility, but also SMC differentiation potential of MSCs was also increased while cultured on the poly-P containing scaffold compared to the empty scaffold. Taken together, our study showed that PLGA-PU-poly-P alone and in combination with MSCs has a promising potential for support urinary bladder smooth muscle tissue engineering.

Efficient smooth muscle cell differentiation of iPS cells on curcumin-incorporated chitosan/collagen/polyvinyl-alcohol nanofibers.

Bladder dysfunction is one of the most common diseases that occur for a number of reasons and the current treatment modalities do not improve much in its recovery process. Tissue engineering in the last two decades has given great hope for the treatment of these disorders. In this study, a composite nanofibrous scaffold was fabricated from chitosan, collagen, and polyvinyl-alcohol polymer blend while curcumin incorporated in scaffold fibers. The scaffold supportive functions from smooth muscle cell differentiation were studied when human-induced pluripotent stem cells were cultured on the scaffolds under differentiation medium. Biocompatibility of the fabricated scaffold increased significantly by incorporating curcumin in the scaffold fibers, where protein adsorption, cell attachment, and viability were increased in the nanofiber/curcumin group compared with the other groups. In addition, the expression level of smooth muscle cell-related genes, including alpha-smooth muscle actin (αSMA), smooth muscle 22 alpha (SM-22a), Caldesmon1, and Calponin1in the stem cells upregulated while cultured in the presence of curcumin, but this increase was significantly improved while cells cultured on the nanofibers/curcumin. In addition, αSMA protein in the cells cultured on the nanofibers/curcumin expressed significantly higher than those cells cultured on the nanofibers without curcumin. It can be concluded that smooth muscle cell differentiation of the induced pluripotent stem cells promoted by curcumin and this promotion was synergistically improved while curcumin incorporated in the nanofibers. Graphical abstract.

Correction to: Prognostic factors in patients with glioblastoma multiforme: focus on the pathologic variants.

Unfortunately, the third author name was incorrectly published in the original publication. The complete correct name should read as follows.

Prognostic factors in patients with glioblastoma multiforme: focus on the pathologic variants.

The aim of this study was to offer predicting factors for survival in adult patients with glioblastoma multiforme. 153 consecutive patients with high-grade glioma (WHO grade IV) were studied in Imam Reza hospital, Kermanshah University of Medical Science, Kermanshah, Iran, between April 2003 and April 2017. All patients treated with surgical resection and standard postoperative radiotherapy (54 Gy). Using the patients' charts and electronic medical records system, the following data were obtained: gender, age, Karnofsky performance status (KPS) score on admission, primary vs. secondary type, extent of surgery, tumor location, tumor size, necrosis size, use of Temozolomide (TMZ), pathology subtype, and immunohistochemistry results. Patients were followed from the time of the surgery until the death occurred. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Survival time curves for various subgroups were compared by the log-rank test. The impact of the suggested prognostic factors on survival was evaluated by univariate and multivariate analyses. Age, gender, KPS, extent of surgery, tumor location, necrosis size, and reoperation in recurrence had not any statistically significant effect on survival. Univariate analysis revealed a significant impact on outcome for pathology subtype (PFS: P < 0.001, OS: P < 0.001), tumor type (primary vs. secondary) (PFS: P = P < 0.001, OS: P < 0.001), tumor size (PFS: P = 0.044, OS: P = 0.04), TMZ therapy (PFS: P < 0.001, OS: P < 0.001), P53 (PFS: P < 0.001, OS: P < 0.001), and Ki67 (PFS: P < 0.001, OS: P < 0.001). In multivariate analysis, independent favorable prognostic factors for survival were pathology subtype (PFS: P < 0.001, OS: P < 0.001), type (PFS: P < 0.001, OS: 0.012), TMZ (PFS: P < 0.001, OS: P < 0.001), P53 (PFS: P < 0.001, OS: P < 0.001), and Ki67 (PFS: P < 0.001, OS: P < 0.001). The results suggest that pathology subtype, primary vs. secondary type, TMZ therapy, P53, and Ki 63 may play an important role in the survival of patients with glioblastoma multiforme. There is no relationship detected between age, gender, KPS, tumor size and location, necrosis size, extent of surgery, reoperation in recurrence, and patient survival.

Antitumoral potential of microvesicles extracted from human adipose-derived mesenchymal stem cells on human breast cancer cells.

AIM OF STUDY: One of the new methods that have promising results is the use of cell-derived microvesicles (MVs) to kill tumor cells. Given that MVs contain apoptotic materials, genes, and proteins, they can interfere with the fate of adjacent cells. MATERIALS AND METHODS: In the present study, after adipose tissue-derived mesenchymal stem cells (AT-MSCs) isolation and characterization, MVs were derived from AT-MSCs and then characterized morphologically by standard error of the mean and size determination by DLS, and after that, the influence of MVs on human breast cancer cells (MCF-7) was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and apoptosis-related gene expression. The raw data were analyzed in SPSS.17 software. RESULTS: The results indicated that MVs have a size range of 500-1500 nm, and the viability of MCF-7 was significantly decreased when treated by different concentrations of MVs and it was confirmed when apoptosis-related genes' expression level was measured by real-time reverse transcription polymerase chain reaction whereas demonstrated that apoptosis genes including Bax, P53, P21, and EP300 (2- ΔΔ CT) and ΔCT values were expressed significantly in MCF-7 treated by MVs higher than those nontreated, and decrease of Bcl-2 expression level in MVs-treated MCF-7 was also significant as an antiapoptosis-related gene. CONCLUSIONS: Taking together, AT-MSC-derived MVs demonstrated anticancer or antitumoral properties on MCF-7 cells, and it could also be effective for other types of cancer cells.

Improved anticancer properties of stem cells derived exosomes by prolonged release from PCL nanofibrous structure.

Systemic chemotherapy as a routine method for the treatment of cancers has several complications. Localized chemotherapy can significantly increase the treatment efficacy and reduce side effects. Here, mesenchymal stem cells derived microvesicles (MVs) was incorporated into Polycaprolactone nanofibers and then the apoptotic behavior of MCF-7 breast cancer cells was investigated while cultured on MVs-Polycaprolactone by using SEM, MTT and apoptotic gene expression. Results demonstrated that MVs-Polycaprolactone group was shown a great apoptosis induction potential into MCF-7 cells and it can be concluded that MVs-Polycaprolactone has a great promising potential to introduce as an in-situ tumor inhibitor construct rather than chemo-drugs.

Down-regulation of CYP27B1 gene expression in Iranian patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) as a complex neurological disease can be due to vitamin D deficiency. CYP27B1 is referred to as a vitamin D metabolizing enzyme. MATERIALS AND METHODS: This study compared the expression level of CYP27B1 in Relapsing-Remitting MS (RRMS) patients with normal individuals in Iran. The RNA was extracted from 50 RRMS patients and 50 normal controls. Quantitative RT-PCR was adopted to measure the expression level of CYP27B1 gene. RESULTS: The expression level of CYP27B1gene was significantly lower in the RRMS patients than their normal counterparts (P value = 0.04). Also, the RRMS females participating had a significant reduction in CYP27B1 gene expression compared to normal females (P-Value = 0.01). In addition, the correlation between CYP27B1 expression level, and the risk of Expanded Disability Status Scale of Kurtzke (EDSS) was not linear. Additionally, there was no significant correlation between expression status of CYP27B1gene and duration of the disease. CONCLUSION: A significant decrease in the expression level of CYP27A1 in female patients could indicate their greater vulnerability to MS than the male patients.

Biodegradability of a polyacrylate superabsorbent in agricultural soil.

Superabsorbent polymers (SAP) are used, inter alia, as soil amendment to increase the water holding capacity of soils. Biodegradability of soil conditioners has become a desired key characteristic to protect soil and groundwater resources. The present study characterized the biodegradability of one acrylate based SAP in four agricultural soils and at three temperatures. Mineralisation was measured as the (13)CO2 efflux from (13)C-labelled SAP in soil incubations. The SAP was either single-labelled in the carboxyl C-atom or triple-labelled including additionally the two C-atoms interlinked in the SAP backbone. The dual labelling allowed estimating the degradation of the polyacrylate main chain. The (13)CO2 efflux from samples was measured using an automated system including wavelength-scanned cavity ring-down spectroscopy. Based on single-labelled SAP, the mean degradation after 24 weeks varied between 0.45% in loamy sand and 0.82% in loam. However, the differences between degradation rates in different soils were not significant due to a large intra-replicate variability. Similarly, mean degradation did not differ significantly between effective temperature regimes of 20° and 30 °C after 12 weeks. Results from the triple-labelled SAP were lower as compared to their single-labelled variant. Detailed results suggest that the polyacrylate main chain degraded in the soils, if at all, at rates of 0.12-0.24 % per 6 months.