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Polypharmacy, defined here as the concomitant use of five or more medications, is a significant health issue, particularly affecting individuals with chronic diseases like hypertension (HTN). To compare individuals with and without HTN in term of polypharmacy, and to investigate correlates of polypharmacy and medication use patterns in individuals with HTN in southwest Iran. This cross-sectional study used the baseline data of 9270 participants of the Pars Cohort Study (PCS) with a mean age of 52.6 ± 9.7 years. Poisson multivariable modeling was applied to identify correlates of polypharmacy, and Lexicomp® was used to assess drug-drug interactions. Anatomical Therapeutic Chemical classification was used to describe the pattern of medication use. The prevalence of polypharmacy in individuals without hypertension was 4.7 % (4.2%-5.2 %) vs. 23.7 % (22.1%-25.3 %) in individuals with hypertension (P < 0.001). Individuals with hypertension from middle-high socioeconomic status (SES) had a 1.51-fold higher prevalence of polypharmacy than vs. low SES. Those with more than three comorbidities had a 5.18 times higher prevalence of polypharmacy than those with isolated hypertension. Calcium channel blockers were the most common antihypertensives (20.9 %). In terms of drug-drug interactions, type C interactions were most prevalent among participants with hypertension and polypharmacy (76.0 %). Our findings imply a fairly high prevalence of polypharmacy and drug-drug interactions among individuals with hypertension; to tackle this issue, we recommend a national pharmacovigilance system, training programs for primary care physicians, public education and awareness campaigns, drug-checking campaigns, targeted screenings to alter modifiable risk factors, and the use of safe combination pills., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Different categories of extracellular vesicles (EVs) are identified based on their origin and formation processes. Among these, exosomes (EXOs) originate from endosomal compartments merging with the plasma membrane, forming small lipid vesicles that transport a range of molecular cargo such as nucleic acids, proteins, and lipids. The composition of EXOs varies depending on their cellular source, encompassing various cell types, including neutrophils, dendritic cells, and even tumor cells. Remarkably, EXOs possess inherent stability, low immunogenicity, and compatibility, making them efficient nano vectors for drug delivery. Imaging techniques like bioluminescence, fluorescence, and nuclear imaging are crucial in non-invasively tracking EXOs within living organisms. This process requires the attachment of radionuclides to the EXO's structure without altering its essential characteristics. Real-time imaging of EXOs is vital for their clinical application, and recent advancements in labeling and tracking methodologies provide insights into biodistribution, functionality, and potential pathways for EXO-mediated drug delivery. This review presents updated progress in the diverse applications of EXOs in targeted imaging across various modalities, where they function as contrast agents facilitating tissue visualization and disease tracking. Consequently, EXOs emerge as promising entities in medical diagnostics and imaging., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aberrant cell proliferation is one of the main characteristics of tumor cells that can be affected by many cellular processes and signaling pathways. Kinesin superfamily proteins (KIFs) are motor proteins that are involved in cytoplasmic transportations and chromosomal segregation during cell proliferation. Therefore, regulation of the KIF functions as vital factors in chromosomal stability is necessary to maintain normal cellular homeostasis and proliferation. KIF deregulations have been reported in various cancers. MicroRNAs (miRNAs) and signaling pathways are important regulators of KIF proteins. MiRNAs have key roles in regulation of the cell proliferation, migration, and apoptosis. In the present review, we discussed the role of miRNAs in tumor biology through the regulation of KIF proteins. It has been shown that miRNAs have mainly a tumor suppressor function via the KIF targeting. This review can be an effective step to introduce the miRNAs/KIFs axis as a probable therapeutic target in tumor cells., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The objective of this work was to review comparisons of the efficacy of 68 Ga-PSMA-11 (prostate-specific membrane antigen) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer among patients undergoing initial staging prior to radical prostatectomy or experiencing recurrent prostate cancer, based on histopathological data. A comprehensive search was conducted in PubMed and Web of Science, and relevant articles were analyzed with various parameters, including year of publication, study design, patient count, age, PSA (prostate-specific antigen) value, Gleason score, standardized uptake value (SUV max ), detection rate, treatment history, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and PI-RADS (prostate imaging reporting and data system) scores. Only studies directly comparing PSMA-PET and mpMRI were considered, while those examining combined accuracy or focusing on either modality alone were excluded. In total, 24 studies comprising 1717 patients were analyzed, with the most common indication for screening being staging, followed by relapse. The findings indicated that 68 Ga-PSMA-PET/CT effectively diagnosed prostate cancer in patients with suspected or confirmed disease, and both methods exhibited comparable efficacy in identifying lesion-specific information. However, notable heterogeneity was observed, highlighting the necessity for standardization of imaging and histopathology systems to mitigate inter-study variability. Future research should prioritize evaluating the combined diagnostic performance of both modalities to enhance sensitivity and reduce unnecessary biopsies. Overall, the utilization of PSMA-PET and mpMRI in combination holds substantial potential for significantly advancing the diagnosis and management of prostate cancer., Competing Interests: Disclosure The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients., Methods: The present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI)., Results: Overall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS., Conclusion: The findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients' access to medical facilities and MS specialists., (Copyright © 2024. Published by Elsevier B.V.)

Background: Magnesium (Mg) is an essential factor in the healing process. This study aimed to evaluate the effect of Mg creams on healing burn wounds in the rat model., Methods: To induce burns under general anaesthesia, a 2 × 2 cm2, 100 °C plate was placed for 12 s between the scapulas in 100 male adult Sprague Dawley rats. Animals were divided into five groups (n = 20); positive control (induced burn without treatment); vehicle control (received daily Eucerin cream base topically); comparative control (induced burn and treated daily with Alpha burn cream topically); Treatment 1 and 2 (received daily Mg cream 2% and 4% topically, respectively). All animals were bled for hematological assessment of malondialdehyde (MDA) and TNF-α and sacrificed on days 0, 1, 7, 14, and 21 after interventions for biomechanical, histological, and stereological studies., Results: Stereologically speaking, in treatment groups an increase in dermal collagen volume and fibroblasts was noticed. In treatment groups, the length of vessels, angiogenesis, and skin stretch increased, but the wound area, MDA, and TNF-α level decreased., Conclusion: Mg cream was effective in healing burns., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Background: Coronary artery bypass surgery is the leading cause of change in the quality of life and pulmonary function of patients. One strategy to enhance lung muscle strength and improve overall quality of life is pulmonary rehabilitation. This study aimed to investigate the impact of incorporating a pulmonary rehabilitation program into phase II cardiac rehabilitation program on the quality of life of patients undergoing coronary artery bypass graft surgery., Methods: This randomized clinical trial study included 53 patients who underwent coronary artery bypass graft surgery at Imam Reza Hospital in Mashhad between September 2019 and March 2020. The research participants were selected based on specific inclusion criteria and divided into two groups. The control group followed the routine rehabilitation program, whereas the intervention group underwent a pulmonary rehabilitation program for 20-30 min after each session of the cardiac rehabilitation program. Data collection tools included a demographic information questionnaire and the Ferrans and Powers' quality of life index. The data were analyzed using the independent t-test, Mann-Whitney test, paired t-test, Spearman correlation, Wilcoxon test, and SPSS25., Results: The mean quality of life score in the intervention group(20.7±1.8) was significantly higher than that of the control group (18.8±2.3)(P < 0.05). Furthermore, the intervention group exhibited significantly higher mean scores in the physical, psychological-spiritual, and family dimensions than the control group(P < 0.05)., Conclusion: The study results demonstrate the positive impact of incorporating a pulmonary rehabilitation program into cardiac rehabilitation on the health-related quality of life of patients undergoing coronary artery bypass graft surgery., Trial Registration: IRCT20190707044132N1., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Immunohistochemistry (IHC) is crucial for breast cancer diagnosis, classification, and individualized treatment. IHC is used to measure the levels of expression of hormone receptors (estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and other biomarkers, which are used to make treatment decisions and predict how well a patient will do. The evaluation of the breast cancer score on IHC slides, taking into account structural and morphological features as well as a scarcity of relevant data, is one of the most important issues in the IHC debate. Several recent studies have utilized machine learning and deep learning techniques to resolve these issues., Materials and Methods: This paper introduces a new approach for addressing the issue based on supervised deep learning. A GAN-based model is proposed for generating high-quality HER2 images and identifying and classifying HER2 levels. Using transfer learning methodologies, the original and generated images were evaluated., Results and Conclusion: All of the models have been trained and evaluated using publicly accessible and private data sets, respectively. The InceptionV3 and InceptionResNetV2 models achieved a high accuracy of 93% with the combined generated and original images used for training and testing, demonstrating the exceptional quality of the details in the synthesized images., (Copyright © 2023 Elsevier Inc. All rights reserved.)

To compare the retinal vascular density (VD), choroidal vascularity index (CVI), and choroidal thickness (CHT) between patients infected with COVID-19 and healthy subjects using non-invasive optical coherence tomography angiography (OCTA) and enhanced depth imaging OCT (EDI-OCT) technique. This case-control study was carried out on patients with COVID-19 and healthy controls. Patients' data were acquired immediately after active infection and three months later. The diagnosis was based on clinical symptoms and a positive PCR test. VDs in superficial and deep capillary plexuses (SCP and DCP) and CHT and CVI were measured and compared between groups. A total of 160 eyes from 80 patients (55% female, mean age 51 ± 13 years) and 80 controls (55% female, mean age 49 ± 12 years) were enrolled. In acute phase infection, the mean foveal avascular zone (FAZ) area was 0.28 ± 0.06 mm 2 and 0.22 ± 0.05 mm 2 in patient and control groups, respectively (P < 0.001). CVI was 61.06 ± 2.59 µm and 72.28 ± 3.84 µm in patients and control groups, respectively (P < 0.001). After three months, the mean FAZ area was 0.28 ± 0.06 mm 2 and 0.23 ± 0.05 mm 2 in the patient and control groups, respectively (P < 0.001). CVI was 60.93 ± 2.11 µm and 72.46 ± 3.80 µm in patients and control groups, respectively (P < 0.001). Subfoveal CHT was not significantly different between groups (P = 0.69). SCP and DCP VDs were significantly less in the patients' group (P < 0.001). In the patients' group, the VDs in the DCP of the whole images and parafoveal DCP (P < 0.001) were reduced significantly after three months in comparison to the acute phase, while the FAZ area, subfoveal CHT, and CVI were not significantly different. COVID-19 infection may be associated with acute and long-term changes of VDs in the retinal and choroidal vasculature without significant effect on the subfoveal CHT., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Vascular endothelial growth factor (VEGF) is a remarkable cytokine that plays an important role in regulating vascular formation during the angiogenesis process. Therefore, real-time detection and quantification of VEGF is essential for clinical diagnosis and treatment due to its overexpression in various tumors. Among various sensing strategies, the aptamer-based sensors in combination with biological molecules improve the detection ability VEGFs. Aptamers are suitable biological recognition agents for the preparation of sensitive and reproducible aptasensors (Apt-sensors) due to their low immunogenicity, simple and straightforward chemical modification, and high resistance to denaturation. Here, a summary of the strategies for immobilization of aptamers (e.g., direct or self-assembled monolayer (SAM) attachment, etc.) on different types of electrodes was provided. Moreover, we discussed nanoparticle deposition techniques and surface modification methods used for signal amplification in the detection of VEGF. Furthermore, we are investigating various types of optical and electrochemical Apt-sensors used to improve sensor characterization in the detection of VEGF biomarkers., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Acetaminophen (Act) overdose is a known inducer of liver failure in both children and adults. Cell annihilation ensues following acetaminophen overdose and its toxic metabolites by depleting cellular GSH storage and increasing ROS levels. Silymarin extract and its major compound silibinin (SLB) possess robust antioxidant properties by inducing ROS elimination; however, low bioavailability and rapid metabolism limit their applications. Herein, we aimed at using SLB liposomes to combat acetaminophen-induced acute liver toxicity., Methods: We have developed a SLB-lipid complex to improve SLB loading efficiency within nanoliposome by using the lipid film method. Liposomes were characterized by using DLS and TEM analysis, and the release pattern, and toxicity profile on the normal cells as well as histopathological and serum analysis were investigated to reveal relevant enzyme activities in an animal model., Results: Data demonstrated that negatively-charged SLB liposomes of 115 nm had homogeneous spherical morphology, and entrapped a considerable quantity of SLB of almost 40%. Liposomes shows a favorable release pattern and were not toxic against NIH3T3 mouse fibroblast cells. The animal study revealed that treatment of mice with SLB nanoliposomes could significantly preserve liver function as revealed by the reduced levels of ALT and AST hepatic enzymes as well as ALP in the serum. Our data indicated that intraperitoneal administration of SLB Lip could significantly reduce ALT enzyme levels (p < 0.05) compared to N-acetylcysteine, while i.v administration resulted in no significant difference compared to control animals with no treatment., Conclusion: The results of this study support the significant hepatoprotective effect of SLB nanoliposomes against acetaminophen-induced toxicity depending on the route of administration., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Obesity is considered one of the independent risk factors for atherosclerosis and is strongly correlated with cardiovascular morbidity and mortality. Previous studies showed carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and nitrite-mediated dilatation (NMD) are reliable non-invasive markers of arterial damage and dysfunction. The aim of this study was to evaluate the effect of bariatric surgery on CIMT, FMD, and NMD markers in patients with obesity. A systematic search was performed in the PubMed, Embase, Scopus, and Web of Science databases until May 2022. All the English-published studies on the effect of bariatric surgery on CIMT, FMD, and NMD were included. A quantitative meta-analysis was performed, as well as subgroup analyses for the type of procedure and duration of follow-up. Meta-analysis of 41 studies with 1639 patients showed CIMT was significantly reduced by .11 mm after bariatric surgery (95% CI, -.14 to -.08; P < .001; mean follow-up = 10.8 mo). The pooled analysis of 23 studies with 1106 patients showed an increase of FMD by 4.57% after bariatric surgery (95% CI, 2.69-6.44; P < .001; mean follow-up = 11.5 mo). The results of a pooled analysis of 12 studies with 346 patients showed a significant increase of NMD by 2.46% after bariatric surgery (95% CI, .99-3.94; P < .001; mean follow-up = 11.4 mo). The random effect meta-regression demonstrated that baseline CIMT and FMD significantly affect the changes in CIMT and FMD. This meta-analysis showed bariatric surgery can improve CIMT, FMD, and NMD markers in patients with obesity. These improvements show the known effect of metabolic surgery in decreasing cardiovascular risk., (Copyright © 2023 American Society for Metabolic and Bariatric Surgery. All rights reserved.)

Statins are the most widely used pharmacological agents for reducing blood cholesterol levels and treating atherosclerotic cardiovascular diseases. Most of the statins' derivatives have been limited by water solubility, bioavailability, and oral absorption, which has led to adverse effects on several organs, especially at high doses. As an approach to reducing statin intolerance, achieving a stable formulation with improved efficacy and bioavailability at low doses has been suggested. Nanotechnology-based formulations may provide a therapeutic benefit over traditional formulations in terms of potency and biosafety. Nanocarriers can provide tailored delivery platforms for statins, thereby enhancing the localized biological effects and lowering the risk of undesired side effects while boosting statin's therapeutic index. Furthermore, tailored nanoparticles can deliver the active cargo to the desired site, which culminates in reducing off-targeting and toxicity. Nanomedicine could also provide opportunities for therapeutic methods by personalized medicine. This review delves into the existing data on the potential improvement of statin therapy using nano-formulations., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cancer cells are surrounded by a complex and highly dynamic tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), a critical component of TME, contribute to cancer cell proliferation as well as metastatic spread. CAFs express a variety of biomarkers, which can be targeted for detection and therapy. Most importantly, CAFs express high levels of fibroblast activation protein (FAP) which contributes to progression of cancer, invasion, metastasis, migration, immunosuppression, and drug resistance. As a consequence, FAP is an attractive theranostic target. In this review, we discuss the latest advancement in targeting FAP in oncology using theranostic biomarkers and imaging modalities such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), fluorescence imaging, and magnetic resonance imaging (MRI)., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cell therapy has reached significant milestones in various life-threatening diseases, including cancer. Cell therapy using fluorescent and radiolabeled chimeric antigen receptor (CAR)-T cell is a successful strategy for diagnosing or treating malignancies. Since cell therapy approaches have different results in cancers, the success of hematological cancers has yet to transfer to solid tumor therapy, leading to more casualties. Therefore, there are many areas for improvement in the cell therapy platform. Understanding the therapeutic barriers associated with solid cancers through cell tracking and molecular imaging may provide a platform for effectively delivering CAR-T cells into solid tumors. This review describes CAR-T cells' role in treating solid and non-solid tumors and recent advances. Furthermore, we discuss the main obstacles, mechanism of action, novel strategies and solutions to overcome the challenges from molecular imaging and cell tracking perspectives., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recent trends in bone tissue engineering have focused on the development of biomimetic constructs with appropriate mechanical and physiochemical properties. Here, we report the fabrication of an innovative biomaterial scaffold based on a new bisphosphonate-containing synthetic polymer combined with gelatin. To this end, zoledronate (ZA)-functionalized polycaprolactone (PCL-ZA) was synthesized by a chemical grafting reaction. After adding gelatin to the PCL-ZA polymer solution, the porous PCL-ZA/gelatin scaffold was fabricated by the freeze-casting method. A scaffold with aligned pores and a porosity of 82.04 % was obtained. During in vitro biodegradability test, 49 % of its initial weight lost after 5 weeks. The elastic modulus of the PCL-ZA/gelatin scaffold was 31.4 MPa, and its tensile strength was 4.2 MPa. Based on the results of MTT assay, the scaffold had good cytocompatibility with human Adipose-Derived Mesenchymal Stem Cells (hADMSCs). Furthermore, cells grown in PCL-ZA/gelatin scaffold showed the highest mineralization and ALP activity compared to other test groups. Results of the RT-PCR test revealed that RUNX2, COL 1A1, and OCN genes were expressed in PCL-ZA/gelatin scaffold at the highest level, suggesting its good osteoinductive capacity. These results revealed that PCL-ZA/gelatin scaffold could be considered a proper biomimetic platform for bone tissue engineering., Competing Interests: Declaration of competing interest The authors declare that there are no Conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Healthcare workers are at risk for HBV infection through percutaneous or mucosal contact with infected blood, body secretions, or blood products or via sharps injury. Hepatitis B vaccination, despite immunogenicity, may not induce a proper immune response in 5-10% of the general adult population. Increased immune response in healthcare providers that do not respond properly to conventional hepatitis B vaccination is an important health challenge. Therefore, the aim of the present study was to evaluate the effectiveness of hepatitis B vaccination plus oral levamisole as adjuvant in healthcare providers non-responsive to routine vaccination., Materials and Methods: The healthcare workers that were non-responsive to previous hepatitis B vaccination were enrolled in a double-blind randomized placebo-controlled clinical trial. The participants were then randomized to two groups including hepatitis B vaccination (as a three-dose series on a 0, 1, and 2-month schedule in the deltoid muscle) plus levamisole (levamisole group) and hepatitis B vaccination plus placebo (placebo group) at a 1:1 ratio. The outcome measure was the HBs antibody titer one month after receiving each dose as well as the seroprotection ratio. The side effects were also evaluated in all participants., Results: In total, 22 subjects finished the trial (11 individual in per group). The median antibody titer one month after receiving the first and third doses increased more in the levamisole group compared to the placebo group but the difference was not significant (p ​= ​0.34, p ​= ​0.66, respectively).The seroprotection ratio after three doses was similarly high in both groups (90.9% in per group). Furthermore, the seroprotection ratio and median antibody titer had no significant correlation with age, sex, BMI, and history of smoking in intervention and control groups (p>0.05). No serious side effects were noted in both groups., Conclusions: Re-vaccination can boost the immune response in healthcare professionals that were non-responsive to previous vaccination although the mean antibody titer was higher in the levamisole group., 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 Objective: The molecular dynamics (MD) simulation is a powerful tool for researching how cancer patients are treated. The efficiency of many factors may be predicted using this approach in great detail and with atomic accuracy., Methods: The MD simulation method was used to investigate the impact of porosity and the number of cancer cells on the atomic behavior of cancer cells during the hematogenous spread. In order to examine the stability of simulated structures, temperature and potential energy (PE) values are used. To evaluate how cell structure has changed, physical parameters such as gyration radius, interaction force, and interaction energy are also used., Results: The findings demonstrate that the samples' gyration radius, interaction energy, and interaction force rose from 41.33 Å, -551.38 kcal/mol, and -207.10 kcal/mol Å to 49.49, -535.94 kcal/mol, and -190.05 kcal/mol Å, respectively, when the porosity grew from 0% to 5%. Also, the interaction energy and force in the samples fell from -551.38 kcal/mol and -207.10 kcal/mol to -588.03 kcal/mol and -237.81 kcal/mol Å, and the amount of gyration radius reduced from 41.33 to 37.14 Å as the number of cancer cells rose from 1 to 5 molecules. The strength and stability of the simulated samples will improve when the radius of gyration is decreased., Conclusions: Therefore, high accumulation of cancer cells will make them resistant to atomic collapse. It is expected that the results of this simulation should be used to optimize cancer treatment processes further., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Physical inactivity is a behavioral and modifiable risk factor for cardiovascular disease. We aimed to assess the association of walking or moderate to vigorous physical activity of various durations with cardiovascular risk in age and sex groups of the adult general population., Methods: This research was a secondary analysis of cross-sectional data from a Brazilian cohort study (2009 to 2014) on the general population in an urban area. Overall, 1208 patients (48.2% males) aged 20-59 years [mean (SD) age = 38.8 (12.0) years] were included., Results: We developed two well-fitted logistic models for investigating the main and interaction effects of physical activity; C-statistic = 74.1 and 80.4, respectively. Older age groups showed a higher association with the risk of cardiovascular disease, adjusted odds ratio OR (95%CI) = 5.28 (2.69, 10.76) for age ≥ 50 years. Walking < 150 min/w was not significant for all age groups (all P ≥ 0.139) compared with the base category (20-29 years). Also, moderate to vigorous physical activity < 150 min/w was not associated with lower cardiovascular risk. However, for moderate to vigorous physical activity ≥ 150 min/w, our results were indicative of a significant protective role for people in 30-39 and ≥ 50 age ranges; OR = 0.20 (0.09, 0.46) and 0.22 (0.10, 0.48), respectively (both P < 0.001)., Conclusion: Our study did not suggest a protective role for walking. However, moderate to vigorous physical activity ≥ 150 min/w was associated with a lower risk of cardiovascular disease in older patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Metal fumes, gases, noise, and radiation are hazardous occupational exposures that may be encountered by welders. We have evaluated DNA damage among welders; the buccal micronucleus cytome (BMCyt) assay was used. Thirty-four exposed welders (cases) and an equal number of non-welders (controls) participated in this study. Cell types including basal, early and late differentiated cells with micronucleus (MN), dense chromatin, karyorrhectic, pyknotic, karyolitic, and binucleated cells (NBUD) were measured. Damage levels among, arc, argon, and CO 2 welders were statistically significantly higher, compared to the control group. Results showed that mean of MN and NBUDs as indicators of DNA damages among arc, argon and CO 2 welding's were significantly higher compared to control group. Also, the mean of DNA damage levels were statistically higher among the arc welders than among the argon or CO 2 welders; and levels were higher among the argon welders than the CO 2 welders. Preventative measures need to be implemented to reduce exposure to harmful agents during welding., Competing Interests: Conflict of interest The authors declare that they have no conflict of interests., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Pericervical ring reconstruction through restoration of pubocervical and rectovaginal fascia is performed concomitantly with sacrospinous hysteropexy as a transvaginal native tissue procedure for vaginal apical prolapse. The main goal of this study was to assess subjective and objective outcomes of sacrospinous hysteropexy and additional pericervical ring reconstruction., Materials and Methods: We conducted a prospective and observational study. All participants underwent sacrospinous hysteropexy and pericervical ring reconstruction and perineorrhaphy. Surgical complications, anatomical and functional efficacy were assessed., Results: 108 cases were included in this study. The mean follow-up timeframe was 18.62 ± 1.22 months (minimum 12 and maximum 26 months). All parameters of subjective outcomes were improved significantly. The overall anatomic success rate was 92.59%. Mean operation time was 50.64 ± 20.8 min. No major intraoperative or postoperative complications were found. There was no statistically significant difference in demographic characteristics including age, BMI, gravidity, medical comorbidities, menopausal status, sexual activity, pretreatment prolapse severity scores between subjects with failure, and good anatomical outcome. Recurrence was mostly observed in patients with higher prolapse stages of anterior and apical compartments. Baseline POP-Q parameters Ba, C, D were significantly higher in cases with failure., Conclusion: Our study disclosed sustainable anatomic and subjective outcomes of modified sacrospinous hysteropexy by means of additional pericervical ring reconstruction., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interests. This study had no financial support., (Copyright © 2023. Published by Elsevier B.V.)

Background: This study assessed: 1) the clinical efficacy of imaging with 68Ga-DOTATATE PET/CT (SSTR (somatostatin receptor)-PET) to detect medullary thyroid carcinoma (MTC); and 2) the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in MTC patients., Materials and Methods: Patients with histologically proven MTC and suspected recurrence following thyroidectomy, based on raised serum calcitonin levels, underwent SSTR-PET. In addition, to evaluate the clinical efficacy and safety of PRRT, the patients with intense uptake on SSTR-PET or 99mTc-octreotide scintigraphy underwent PRRT. The Common Terminology Criteria for Adverse Events (version 4.03) was used to grade adverse events after PRRT. Treatment response was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD)., Results: Twenty MTC patients (10 male, 10 female) with a median age of 48.5 years underwent SSTR-PET. SSTR-PET was positive in 17/20 patients (85%). Four of the 17 patients with positive SSTR-PET were scheduled for PRRT. In addition, 2 patients had positive 99mTc-octreotide scintigraphy results (Krenning score ≥ 2) and were scheduled for PRRT. Two of the 6 patients who underwent PRRT showed PR, 2 SD and 2 PD. Two patients died during the follow-up period. Median overall survival was 19 months (95% CI: 5.52-29.48). There were no cases of significant toxicity., Conclusion: Radiolabeled somatostatin analogs are contributive for the management of recurrent MTC. 68Ga-DOTATAE PET-CT showed a relatively high detection rate in recurrent MTC. In addition, PRRT with 177Lu-DOTATATE was found to be a safe alternative therapeutic option for MTC., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: Radiomics in Ultrasound (US) imaging has been investigated for the prediction and prognosis of cancers. However, inter-scanner and intra-scanner variations may affect the reproducibility of radiomics results. This study aims to evaluate the reproducibility of US textural radiomics features across various scan settings and scanner vendors., Materials and Methods: US images in quality control (QC) phantom were obtained by three scanners (Philips, Samsung, and Siemens) with different scan settings and parameters. Circular regions of interest (ROIs) inside isoechoic, hypoechoic, and hyperechoic objects were manually delineated. Forty textural radiomics features were extracted from each ROI, and then the robust features that could distinguish different echogenic objects were obtained by the Mann-Whitney U test. Reproducibility of the robust radiomics features was assessed by the intraclass correlation coefficient (ICC) and coefficient of variation (CV); ICC>0.90 and %CV<20 were considered reproducible., Results: According to the Mann-Whitney U test results, ten robust features could differentiate the hypoechoic, and 15 robust features could differentiate the hyperechoic objects from the isoechoic objects (P<0.001). The total ICC of the robust features for each echogenic object was >0.95 in different scanners and scan settings. Four and seven features were individually reproducible (%CV < 20, ICC>0.90) in hypoechoic and hyperechoic objects, respectively. Also, four features seem reproducible by changing the ROI location across the horizontal and vertical lines for both convex and linear array transducers., Conclusions: Most of the US textural radiomics features in this study were not reproducible. However, several features showed high reproducibility at different scan settings and scanners. These features may also be reproducible when ROI size and location change slightly., (Copyright © 2022. Published by Elsevier Inc.)

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Neisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000-2020) in the world., Methods: Published researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis., Results: The overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate., Conclusions: To properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Aim of the Work: To investigate the frequency, clinical characteristics and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in rheumatic diseases patients., Patients and Methods: One thousand patients with rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), systemic sclerosis (SSc), Sjögren's syndrome (SS), Behçets disease (BD), vasculitis, idiopathic inflammatory myositis (IIM), relapsing polychondritis, sarcoidosis and antiphospholipid syndrome (APS) were studied. The following data were collected: age, sex, disease diagnosis, rheumatic disease medication. Rheumatic diseases patients were divided into two groups of infected and non-infected patients with COVID-19 and collected data were compared., Results: The 1000 patients mean age was 43.4 ± 13 years and 84.1% were females. The main diagnosis was RA (37.1%), followed by SLE (23.8%), SpA (13.4%), SSc (12.4%), vasculitis, BD and rhupus in 2.4%, 2.3% and 2.2% respectively, SS and SSc in 0.7% each. Most patients were taking glucocorticoids (78.4%). A large majority of patients were taking at least one of the cDMARDs. 16.1% were taking biologic therapy. 221 rheumatic diseases patients with COVID-19 were identified. Of these, 38 patients (17.2%) were hospitalized and 9 patients (4.1%) died. No significant difference was observed for compared variables in patients with and without COVID-19 except for prednisolone >20 mg/d (0.64% vs 2.26%; p = 0.048)., Conclusion: Most rheumatic diseases do not seem to be a risk factor for developing COVID-19 infection and despite immunosuppressive therapies, there is no poorer outcome. Only, patients using prednisolone >20 mg/d are at higher risk of developing COVID-19 infection., 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., (© 2021 THE AUTHORS.)

DNA methylation, as an epigenetic mechanism, occurs by adding a methyl group of cytosines in position 5 by DNA methyltransferases and has essential roles in cellular function, especially in the transcriptional regulation of embryonic and adult stem cells. Hypomethylation and hypermethylation cause either the expression or inhibition of genes, and there is a tight balance between regulating the activation or repression of genes in normal cellular activity. Abnormal methylation is well-known hallmark of cancer development and progression and can switch normal stem cells into cancer stem cells. Cancer Stem Cells (CSCs) are minor populations of tumor cells that exhibit unique properties such as self-regeneration, resistance to chemotherapy, and high ability of metastasis. The purpose of this paper is to show how aberrant DNA methylation accumulation affects self-renewal, differentiation, multidrug-resistant, and metastasis processes in cancer stem cells., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Coronavirus disease-2019 (COVID-19) is a novel infectious disease, which presents with various clinical manifestations. There is growing evidence of an association between COVID-19 infection and autoimmune diseases. The aim of this case report was to demonstrate the association of COVID-19 infection and the development of systemic lupus erythematosus (SLE)., Case Presentation: A 38 year old Iranian woman presented with progressive icterus, pleuritic chest pain, palpitation, dyspnea, photosensitivity and arthralgia 18-days after COVID-19 symptoms proved by a positive polymerized chain reaction (PCR). The chest and abdomen computerized tomography (CT) scan showed pericardial and pleural effusion and enlarged liver and abdominal lymph nodes. Antinuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-ds DNA) antibody and perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA) were positive. She was diagnosed as SLE and was successfully treated with prednisolone 30 mg daily, hydroxychloroquine 200 mg daily and azathioprine 150 mg daily and she remarkably improved. Repeated anti-ds DNA antibody was positive. Due to nausea and abdominal discomfort, azathioprine was discontinued and replaced with mycophenolate mofetil 1500 mg daily. In the article, similar cases were presented; the mean interval between COVID symptoms and SLE presentations was 24.86 days. Pulmonary and renal involvements were the most common presentations of SLE triggered by COVID-19. The most frequently reported autoantibody was ANA., Conclusion: It is necessary to be aware of the development of lupus disease in COVID-19 infected patients, because prompt diagnosis and treatment is very important to improve their outcome., 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., (© 2021 THE AUTHORS.)

Pediatric acute lymphoblastic leukemia (pALL), a malignancy of the lymphoid line of blood cells, accounts for a large percentage of all childhood leukemia cases. Although the 5-year survival rate for children with ALL has greatly improved over years, using chemotherapeutics as its first-line treatment still causes short- and long-term side effects. Furthermore, induction of toxicity and resistance, as well as the high cost, limit their application. Phytochemicals, with remarkable cancer preventive and chemotherapeutic characteristics, may serve as old solutions to new challenges. Bioactive plant secondary metabolites have exhibited promising antileukemic and adjunctive effects by targeting various molecular processes, including autophagy, cell cycle, angiogenesis, and extrinsic/intrinsic apoptotic pathways. Although numerous reports have shown that various plant secondary metabolites can interfere with the progression of malignancies, including leukemia, there was no comprehensive review article on the effect of phytochemicals on pALL. This systematic review aims to provide critical and cohesive analysis of the potential of various naturally-occurring plant secondary metabolites in the management of pALL with the understanding of underlying molecular and cellular mechanisms of action., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The neutrophil to lymphocyte ratio (NLR) has been reported to be associated with clinical outcomes of patients with severe traumatic brain injury (TBI). This study aimed to evaluate the correlation between the dynamics of NLR and clinical outcomes of pediatric patients with moderate to severe TBI., Methods: We retrospectively evaluated the clinical data of a total of 374 pediatric patients with moder-ate to severe TBI who were treated in our department between May 2016 and May 2020. Clinical and laboratory data including the NLR upon admission and the NLR on hospital day four were collected. Poor clinical outcome was defined as Glasgow Outcome Scale (GOS) of 1-3. Multivariable logistic regression analyses were performed to investigate the correlation between the dynamics of NLR and clinical outcome., Results: Three hundred seventy-four pediatric patients (mean age 7.37 ± 3.11, 52.7% male) were evaluated. Based on the ROC curves, a value of 5 was determined as the NLR cut-off value. The corresponding cutoff value for delta NLR was 1. The Glasgow Coma Scale (GCS) (OR, 3.42; 95% CI: 1.88-5.28; P <0.001), the light reflex (OR, 1.79; 95% CI: 1.34- 2.84; P = 0.027), the Rotterdam CT score (OR, 2.71; 95% CI: 1.72-4.13; P = 0.021), and delta NLR (OR, 1.71; 95% CI: 1.13- 2.52; P = 0.034) were identified as independent predictors for unfavorable outcomes in multivariable logistic regression analysis., Conclusions: The result of the present study suggest that delta NLR could be a predictor of poor clinical outcome of pediatrics with moderate to severe TBI. This cost-effective and easily available biomarker could be used to predict clinical outcomes in these patients., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

This paper aimed to provide an innovative 2D phase space model and evaluate its performance in categorizing electroencephalogram (EEG) signals of normal and epileptic patients. The main contributions of the current study are as follows. (1) For the first time, it was proposed a new 2D model based on a 2-piece Rose Spiral Curve (RSC) in EEG analysis. (2) The trajectory patterns of the model were examined for signals of different natures, including constant, periodic, random, and EEG. (3) It was presented some benchmarks for quantifying the trajectory patterns. (4) Applying these measures, support vector machine, Naïve Bayes, AdaBoost, and K-nearest neighbor were used in the epileptic EEG classification problem to estimate the method efficiency. Bonn database, which takes account of EEG signals of healthy, in the course of an epileptic seizure occurrence, and seizure-free cases, was assessed. The results indicated that the proposed framework provided a correct rate of 100% for recognizing healthy subjects and the EEGs with seizure activity. Additionally, seizure-free brain activity was classified with an accuracy of 96.7%. To conclude, the proposed RSC model can be suitable for serving as a computer-aided diagnosis tool for epileptic seizures., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The aim of the present study is to investigate the trend of suicide and its attempt and the factors related to completed suicide during a 5-year period (2014-2019) in South Khorasan province, Iran. Data analysis was performed using chi-square, independent t-test and backward logistic regression in SPSS ver. 16. Cochran-Armitage test was used to evaluate the trends of suicide attempt and completed suicide. P-value < 0.05 was considered as the significance level. There was a significantly higher rate of suicide attempt among women and a significantly higher rate of completed suicide among men (p = 0.007). The incidence of suicide attempt (p = 0.001) and suicide deaths (p = 0.003) have also increased significantly during these years and the most common method of suicide attempt is drug poisoning. Also increasing age, rural residence, having a history of mental disorder, marital separation and lower level of education led to a significant increase in the rate of completed suicide (p < 0.001). The present study showed no significant relationship between the history of suicide attempt and completed suicide (p = 0.19). The rate of suicide attempt was higher among women and the rate of completed suicide was higher among men. The rate of suicide attempts and completed suicides has increased during these five years. Factors such as untreated mental disorders, living in rural areas, separation, and older age were considered as risk factors for completed suicide. On the other hand, higher education level has played a protective role in this regard., (Copyright © 2021. Published by Elsevier B.V.)

Background: In this trial, additive effects of acupuncture to selective serotonin reuptake inhibitors (SSRIs) treatment for reducing anxiety, were investigated., Methods: 112 patients with anxiety disorder were randomly divided into three groups including SSRIs alone (drug group), SSRIs with sham acupuncture (control group) and SSRI with acupuncture (acupuncture group), and treated for 4 weeks. At the beginning of the study and on day 28, Spielberger State-Trait Anxiety Inventory (STAI) questionnaire was completed and serum levels of cortisol were measured., Results: 105 patients completed the treatment period. STAI score showed significant differences among the three groups at the end of the study; importantly, changes in STAI score in the acupuncture group were significantly larger than the other groups. A decrease in cortisol levels was observed in all groups; though statistically non-significant, this decrease in the acupuncture group was larger., Conclusion: Acupuncture combined with SSRIs can significantly improve anxiety state compared to anti-anxiety therapy using SSRIs alone., (Copyright © 2021. Published by Elsevier Ltd.)

Chemotherapy drugs are still one of the first treatment options used in many cancers; however, problems such as cytotoxic side effects on normal cells after systemic administration and resistance to treatment have reduced the use of chemotherapeutics day by day. Targeted delivery of these drugs to the tumor site and sensitization of cancer cells to death induced by chemotherapy drugs are ways that can overcome the limitations of the use of these drugs. In this study, we designed and generated a novel nanocarrier composed of chitosan lactate nanoparticles (NPs) functionalized by HIV-1 derived TAT peptide (Transactivating transcriptional activator) and hyaluronate (HA) to deliver CD73 siRNA and doxorubicin to 4T1 and CT26 cancer cells, both in vivo and in vitro, as a novel combinatorial treatment strategy. The CD73 molecule plays a key role in many cancer cell behaviors such as proliferation, angiogenesis, metastasis, imunosuppression, and resistance to chemotherapy. Therefore, we decided to reduce the side effects of DOX by simultaneously transmitting CD73 siRNA and DOX by CL-TAT-HA NPs, increase the susceptibility of cancer cells to DOX-induced cell death, and stimulate anti-tumor immune responses, for the first time. These results indicated that simultaneous transfer of CD73 siRNA and DOX to cancer cells (4 T1 and CT26) increased cell death and inhibited the prolifration and spread of cancer cells. Also, the preferential aggregation of NPs in the tumor microenvironment reduced tumor growh, promoted the survival of tumor-bearing mice, and induced anti-tumor immune responses. These findings indicate that CL-TAT-HA NPs are a good candidate for targeted siRNA/drug delivery to cancer cells and the simultaneous transfer of CD73 siRNA and DOX to cancer cells using this nanocarrier can be used to treat cancer., (Copyright © 2021. Published by Elsevier B.V.)

Aims: Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death., Materials and Methods: We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo., Key Findings: The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses., Significance: These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that affects predominantly small- sized vessels. A causal relationship between viral infections and vasculitis has been postulated.Aim of the workTo present the concomitant association of coronavirus disease 2019 (COVID-19) infection with MPA in an elderly Iranian male., Case Presentation: A 67 year old Iranian man with the history of COVID-19 infection and a positive polymerized chain reaction (PCR) test four weeks before admission to the neurology department with acute onset pain, numbness and progressive weakness in both hands grip, sudden left foot drop and paresthesia. Erythrocyte sedimentation rate (ESR) was 95 mm/hr, ferritin 912 ng/ml and C-reactive protein (CRP) positive, proteinuria 1.1 g/24 h and markedly elevated perinuclear (P-ANCA): 526 IU/ml. Diagnosis of MPA was held presenting with mononeuritis multiplex, glomerulonephritis followed by diffuse alveolar hemorrhage and infiltration of lymphocytes in muscle fibers and vessels wall in sural nerve biopsy. He was successfully treated by methylprednisolone (1 g/day for 3 days) followed by 1 mg/kg with gradual tapering along with cyclophosphamide (CYC) (2 mg/kg). Intravenous immunoglobulin (IVIG, 2 g/kg in four divided doses) started for the management of inflammatory mononeuritis multiplex with gradual improvement. During hospitalization, plasmapheresis was performed due to alveolar hemorrhage for 5 day. The patient returned home on day 32 and followed-up in the rheumatology clinic with improvement of muscle power and handgrip strength., Conclusion: Vasculitis is potentially one of COVID-19's presenting symptoms and prompt diagnosis and treatment is crucial in improving outcome of patients., 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., (© 2021 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Immunotherapy methods using potential tumor microenvironment modulators have elicited durable therapeutic responses in cancer treatment. Immune checkpoint molecule programmed cell death-ligand 1 (PD-L1) and oncogenic transcription factor STAT3 (signal transducer and activator of transcription-3) assigned as inhibitory targets of our study and particular delivery system designed to deliver small interfering RNAs (siRNAs) to silence the targeted genes. Generated trimethyl chitosan (TMC) and thiolated chitosan (TC) nanoparticles (NPs) conjugated with HIV-1-derived TAT peptide and HA (hyaluronic acid) exhibited eligible physicochemical characteristics, notable siRNA encapsulation, serum stability, non-toxicity, controlled siRNA release, and extensive cellular uptake by cancer cells. Dual inhibition with STAT3/PD-L1 siRNA-loaded HA-TAT-TMC-TC NPs led to promising results, including significant downregulation of PD-L1 and STAT3 genes, striking suppressive effects on proliferation, migration, and angiogenesis of breast and melanoma cancer cell lines, and restrained tumor growth in vivo. These findings infer the capability of HA-TAT-TMC-TC NPs containing STAT3/PD-L1 siRNAs as a novel tumor-suppressive candidate in cancer treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The survival rate following Cardiopulmonary Resuscitation (CPR) has been reported to be 7-26.7%. Various studies have shown that CPR failure is high in many countries. This study was aimed to explore the barriers to the success of CPR from the perspective of Iranian nurses., Methods: Participants were 14 Iranian nurses recruited through purposive sampling. In-depth semi-structured interviews were used to collect data. Data were analyzed using qualitative content analysis., Results: The barriers to successful CPR were developed in three main categories and nine subcategories. Some of the barriers to CPR success were: "delayed attendance of the CPR team and start of CPR", "inadequate experience and skill of the CPR team", "poor access to special units", "insufficient and deficient CPR equipment", "poor CPR location", "critical clinical conditions of the patient", and "interference of the patient's family members., Conclusion: The results showed that human and environmental factors can result in CPR failure. These barriers can be minimized by measures such as empowerment of the CPR team, and providing the necessary facilities and equipment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We examined electrolyte imbalance and blood sugar levels in patients with COVID-19 who had no underlying disease. This cross-sectional study in a clinical center was performed in Kermanshah, west of Iran. All patients who had a record of magnesium (Mg 2+ ), potassium (K + ), sodium (Na+), and fasting blood sugar (FBS) tests in their clinical files at the time of admission to the hospital from April 21 to July 12, and didn't have a history of an underlying disease, were included in the study. Patients were divided into outpatient (as less severe COVID-19) and intensive care units (ICU) (as severe COVID-19). For statistical analysis of collected data, the SPSS software (version 16) was used. Among a total of 134 patients, 58 cases (24 ICU and 34 outpatients) were included in the study. The mean and median age was 56 and 62 years, respectively. From all included, 33 men (57%), 25 women (43%), 52 urban (89.7%), 6 rural (10.3%), 41 alive (70.7%), and 17 died (29.3%) were recorded. From all included patients, 49.1% hyperglycemia, 38% hyponatremia, 7.3% hypokalemia, and 32% hypomagnesemia were observed. Unlike the mean of age and the level of K+, there was a statistically significant difference between the outpatient and ICU groups in terms of Mg 2+ , Na + , and FBS (p < 0.05). Hyperglycemia and electrolyte imbalance in COVID-19 patients is feasible. Therefore, notice to measuring these cases and monitoring the patient can be effective in the treatment process and prevent the serious complications of the disease., (© 2020 The Authors.)

In this study using phospholipids with high transition temperature and taking advantage of PEGylation, we designed liposomal formulation targeted with folic acid (FA) to improve the stability of liposomes with high penetration efficiency at the same time. The results of characterization demonstrated that liposomal formulations are in range of 150-210 nm size with negative surface charge. The results of cell uptake indicated that FA conjugation resulted in the more uptake of insulin. However, the results of transepithelial electrical resistance (TEER) showed no statistical differences among the formulations. The results of biodistribution also demonstrated that PEGylated liposome targeted with FA had more residence time in stomach and intestine along with higher amounts in blood and liver. The anti-diabetic effects of formulation in vivo indicated the efficacy of PEGylated liposome targeted with FA had promising results in decreasing blood glucose and increasing insulin levels. The results of this study indicated that using phospholipids with high Tm along with PEGylation and using targeting ligand could improve efficiency of oral delivery of liposomes which merit further investigation., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Non-small cell lung carcinoma (NSCLC) is among the most lethal lung cancers responsible for 80-85% of death. α v β 3 integrin receptor subtype has been identified as a lung cancer biomarker since its expression correlates with tumor progression and metastasis. The extracellular domain of the receptor forms a binding site for RGD-based sequences. Therefore, specific targeting of α v β 3 integrin receptors by these short peptides can be an excellent candidate for cancer imaging and therapy. In this research, the radiolabeling of DOTA-E(cRGDfK) 2 with 177 Lu was efficiently implemented. The Log P value, in vivo, in vitro, metabolic stability, cellular uptake and specific binding of the radiopeptide was determined. The tumor targeting capacity and the therapeutic potential of the radiotracer was studied in A549 tumor-bearing mice. Imaging studies at different time intervals were performed by SPECT/CT. Radiochemical purity of more than 99% and Log P of -3.878 was obtained for 177 Lu-labelled peptide. Radiotracer showed favorable in vivo, in vitro and metabolic stability. The radiopeptide dissociation constant (K d ) was 15.07 nM. Radiopeptide specific binding was more than 95%. Biodistribution studies showed high accumulation of the radiopeptide in tumor and rapid excretion by urinary route. Maximum tumor uptake was at 4 h post-injection. Following administration of this radiopeptide to mice, not only tumor growth was suppressed, but significant tumor shrinkage was also observed. In conclusion, this radiopeptide can be employed for staging, follow-up imaging and as peptide receptor radionuclide therapeutic agent allowing efficient therapy for NSCLC and other cancers overexpressing α v β 3 integrin receptors., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The effects of oleoylethanolamide (OEA) on NAFLD are yet to be examined in human. The objective of the present study was to examine the effects of OEA supplementation along with weight loss intervention on the expression of PPAR-α, uncoupling proteins 1and 2 (UCP1 and UCP2) genes in the peripheral blood mononuclear cells (PBMCs), metabolic parameters, and anthropometric indices among obese patients with NAFLD. In this triple-blind placebo-controlled randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group along with calorie-restricted diets for 12 weeks. At pre-and post-intervention phase, mRNA expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, serum levels of metabolic parameters as well as diet and appetite sensations were assessed. There was a significant increase in the expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, compared to the placebo at the endpoint. A significant decrease in the anthropometric indices, energy and carbohydrate intakes, glycemic parameters, except for hemoglobin A1c concentration was also observed in the OEA group, compared to the placebo group. OEA treatment significantly resulted in decreased serum levels of triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, increased serum levels of high-density lipoprotein cholesterol (HDL-C), and improved appetite sensations. Importantly, a significant improvement in TG, ALT, AST, ALT/AST, HDL-C levels as well as appetite sensations by OEA were under the influence of body mass index (BMI). Although liver steatosis severity was significantly reduced in both groups, the between-group differences did not reach statistical significance (P = 0.061). In conclusion, the present study, for the first time, revealed that OEA supplementation significantly improved anthropometric and metabolic risk factors related to NAFLD., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: It has been shown that N-acetylcysteine may be useful in correcting postoperative hepatic and renal function in many pathological conditions. The present study aimed to examine the effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in patients with obstructive jaundice., Methods: & Materials: A total of 30 patients with obstructive jaundice who were candidates for bypass surgery were enrolled in this randomized clinical trial. In the case group, intravenous N-acetylcysteine (200 mg/kg per hour in the first 8 h, followed by 100 mg/kg per hour for another 16 h, the same dose for another 24 h) was administered postoperatively. Liver and renal function tests (serum AST, ALT, ALP, GGT, bilirubin, and creatinine) were compared between two groups, as well as duration of hospitalization and ICU stay., Results: Postoperatively, decrease in mean serum AST (p = 0.01), ALT (p = 0.02), ALP (p = 0.01), GGT (p = 0.04) and bilirubin (total, p = 0.02, direct, p = 0.01) levels compared to the preoperative values was significantly more among cases compared to those in controls. Changes in serum creatinine, however, did not differ significantly between two groups (p = 0.18). Hospital and ICU stays were also not different between two study groups (p = 0.27 and p = 0.94 respectively)., Conclusion: On the basis of our findings, intravenous N-acetylcysteine in patients with obstructive jaundice could significantly preserve liver function after bypass surgery. Effect of this medication on renal function; however, was not statistically significant., Trial Registration: Iranian Registry of Clinical Trial: IRCT2016041016473N7., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Purpose: Autoimmune polyendocrine type 1 (APS-1) is a complex inherited autosomal recessive disorder. Classically, it appears within the first decade of life followed by adrenocortical insufficiency, mucocutaneous candidiasis, Addison's disease, and hypoparathyroidism. The clinical phenotype of APS-1 varies depending upon mutations in the autoimmune regulator gene (AIRE) on chromosome 21q22.3., Methods: In this study, we performed Sanger sequencing ofAIRE in Iranian patients to identify different variants and probable new mutations corresponding to a clinical diagnosis of APS-1., Results: After analyzing 14AIRE exons, we detected a novel insertion mutation in exon 2 in a patient who presented with severe APS-1, Lys50AsnfsX168. Furthermore, the known mutations in AIRE, including Arg139X, Arg257X, and Leu323SerfsX51, were detected in enrolled patients., Discussion: According to our results, sequencing analysis ofAIRE provides a useful screening method to diagnose patients with incomplete or unusual clinical presentations of APS-1., (Copyright © 2019. Published by Elsevier GmbH.)

Background: Reconstruction of the nasal midvault is an important component of successful rhinoplasty outcomes. Use of the autospreader flap is a beneficial technique for preserving the middle vault. In the present study, we evaluated the esthetic and functional outcomes of this technique in patients without notable dorsal hump reduction., Methodology: A nonrandomized clinical trial was performed from December 2017 to April 2018 with a minimum follow-up time of 6 months. From among patients seeking rhinoplasty, 38 were eligible for inclusion in the study. The autospreader flap was used to recreate the middle vault in patients undergoing open rhinoplasty, with up to 2 mm bony and cartilaginous dorsal hump removal. Preoperative and postoperative standard photographs were obtained. Assessment of patients was based on Rhinoplasty Outcome Evaluation (ROE) and Nasal Obstruction Symptom Evaluation Scale (NOSE) scores. Objective assessment included quantitative analysis of anthropometric angles, mean dorsal width, nasal length, and projection which was performed on standard pre- and postoperative photos., Results: Overall, the patients had statistically significant improvement in their postoperative NOSE scores (9 vs. 6.92, p = 0.0001). The majority of patients were satisfied with the postoperative appearance of their noses. The mean nasal dorsal width (NDW) decreased postoperatively (43% vs. 36%). No difference was found between the mean height of the nose and projection pre- and postoperatively. There was a significant postoperative increase in the nasolabial angle and reduction in nasal length., Conclusions: The autospreader flap is an effective technique for preservation and restoration of the middle vault and dorsal esthetic line in cases of less than 2 mm dorsal hump reduction. Nasal function can be improved while achieving good cosmetic outcomes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Gastric cancer (GC) as the third most common cause of cancer-associated mortality worldwide is one of the cancers with very high heterogeneity. Cancer stem cells (CSCs) as a small subset of cancer cells in solid tumors with the self-renewal, differentiation and tumorigenic ability are responsible for tumor initiation, progression, recurrence, metastasis, and resistance to current treatments. Therefore, eradication of CSCs is very vital to cure cancer. Here, we first isolated and identified sphere-forming cells in tumor tissue from four GC patients and then analyzed T cell responses induced by monocyte-derived dendritic cells (DCs) loaded with total mRNA of sphere-forming cells in terms of interferon-gamma (IFN-γ) gene expression and specific cytotoxicity. Spheroid colonies were formed in serum-free media. Sphere-forming cells dissociated from tumorspheres heterogeneously expressed CD44, CD54, and epithelial cell adhesion molecule (EpCAM) markers and generated one tumor in nude mice. These results demonstrated that gastric CSCs were enriched in tumorspheres. Cytokine-matured DCs loaded with mRNA of sphere-forming cells were able to induce IFN-γ gene expression in T-lymphocytes after a 12-day co-culture. mRNA level of IFN-γ gene in these lymphocytes was more highly expressed compared to stimulated T-lymphocytes by DCs transfected with normal tissue (6.4-9.39 folds). Cytotoxic activity of primed T-lymphocytes with antigens of sphere-forming cells was significantly higher than normal tissue antigens and mock DCs (P ≤ 0.0001). Taken together, DCs loaded with mRNA of sphere-forming cells that elicit effectively specific T cell-mediated immune responses in vitro, may be considered as a promising therapeutic vaccination in GC patients in future., (Copyright © 2019 Elsevier Inc. All rights reserved.)