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Purpose: Iron toxicity occurs under iron-overloaded settings, such as a high iron diet and blood transfusion, and damages important organs. Vanillin has been proven to have potential iron chelation capability. Given the negative effects of commonly used iron chelators like deferoxamine (DFO), we sought to examine the iron chelation potency of vanillin and evaluate its potential effect in the treatment of iron overload-related disorders., Methods: 42 male NMRI mice were prepared for this purpose, and except for the negative control group, iron overload conditions were generated in them by injecting iron. Then normal saline (as a control), vanillin, and DFO (n = 7) were subsequently given to iron-overloaded mice. In the following, the activity of antioxidant enzymes catalase and superoxide dismutase were measured in the blood serum, brain, kidney, spleen, lung, and liver tissues of mice. Furthermore, the level of lipid peroxidation was determined by measuring the amount of malondialdehyde. Also, Perl's and H&E staining were used to examine the physiopathology changes of tissues., Findings: Vanillin, a natural antioxidant compound, outperformed deferoxamine, a chemical iron chelator. Along with a decrease in iron content, the activity of catalase and superoxide dismutase enhanced in the iron-overloaded groups that were treated with vanillin. The level of lipid peroxidation was also declined in the iron-overloaded mice receiving vanillin., Conclusion: Vanillin can be used as a suitable substitute for chemical chelators with fewer side effects and equivalent efficiency. We encourage the use of this compound as a natural iron chelator following performing additional safety and efficacy studies., 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 B.V. All rights reserved.)

Background: Knowledge about the associated factors with epilepsy in the elderly in Iran is limited. Therefore, this study aimed to determine the prevalence of epilepsy and associated factors in Amirkola elderly patients., Methods: This cross-sectional study is a part of a comprehensive and cohort research of "The Amirkola Health and Ageing Project". The Mini-mental State Examination was used for cognitive impairment, Geriatric Depression Scale for psychiatric diseases and the Physical Activity Scale for Elderly questionnaire for physical activity., Results: The prevalence of epilepsy was 35 from 1482 participants (24/1000). The significant association between Parkinson's Disease (OR=6.25, 95%CI=1.35-28.4, P=0.001), falls (OR= 3.81, 95%CI=1.62-8.97, P=0.001), depression (P=0.001), hyperphosphatemia (P=0.039) and hypokalemia (P= 0.031) concluded with epilepsy. Past history of stroke (6 % versus 2%, OR= 2.8, 95%CI, 0.97-8.27, P=0.07), increased serum level of triglyceride (OR= 1.96, 95%CI= 0.99-3.88, P=0.06) and low-density lipoprotein (LDL) (P=0. 45) were seen in epileptic patients vs. non-epileptic patients., Conclusion: Parkinson's disease, frequency of falls and depression were the associated factors in epileptic patients and a correlation between past history of stroke, increased serum level of triglyceride and LDL with epilepsy were seen. Associated factors required screening, diagnosis and treatment., Competing Interests: There was no conflict of interest.

Aims: Evaluate patient-reported liver symptoms during treatment for chronic hepatitis B viral (HBV) infection and associations between changes in symptoms and levels of alanine aminotransferase (ALT) and viral markers., Methods: Data from 200 participants in the Hepatitis B Research Network Immune Active Trial who completed symptom assessments were analyzed. Patients were treated with tenofovir, with or without peginterferon (TDF + PegIFN vs. TDF alone) for 192 weeks. Participants completed a Symptom Checklist at baseline and every 4-12 weeks. A total symptom score was created, ranging from 0 (none) to 40 (severe). The SF-36 was completed every 48 weeks. Associations of symptom scores with ALT and viral markers were evaluated at baseline and end of treatment., Results: Participants were 65% male, 83% Asian, with a mean age of 42. Baseline symptoms were mild (median = 2, range 0-25) and associated with baseline ALT, HBV DNA levels and HBeAg + status. Patients on TDF alone experienced a more rapid and greater improvement in symptoms, but by week 192, symptom improvement was similar in both groups (54% vs 36%). Symptom improvements correlated with ALT and HBV DNA, most markedly among those with symptoms at baseline. Most patients (4 out of 6) who achieved HBsAg loss experienced symptom improvements. Overall, SF-36 scores did not change with treatment., Conclusions: Reduction in ALT and HBV DNA levels with therapy are associated with significant improvement in liver symptoms such as fatigue and pain over the liver, especially among those with higher ALT, HBV DNA, symptoms and HBeAg + status prior to treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coxiella burnetii, a zoonotic pathogen, is the causative agent of Q fever, an endemic disease in Iran. However, there is currently a lack of available data on the genotypes of C. burnetii in the country. Here, we typed 26 C. burnetii isolates detected in milk, abortion, cotylodon, and cardiac valve samples from various geographical areas and hosts (7 cattle, 8 goats, 10 sheep, and 1 human) using Multilocus Variable Number Tandem Repeat Analysis (MLVA/VNTR) with five loci:ms24, ms27, ms28, ms33, and ms34. As IS1111 was observed to be spontaneously inserted in locus ms23 across all of our examined C. burnetii samples, five loci were employed for MLVA/VNTR genotyping. Among the 26 C. burnetii strains, 22 distinct genotypes (A-V) were identified in the discriminative loci. In silico analysis categorized Iranian C. burnetii strains into five genomic groups along with seven singletons, representing 11 exiting clonal complexes worldwide. Clusters 10 and 11 exclusively consisted of Iranian samples. These findings revealed high genotyping diversity among C. burnetii isolates in Iran. The genotypes circulating in Iran differed significantly from those found in other regions worldwide. To gain a comprehensive understanding of Q fever epidemiology in Iran, it is crucial to conduct large-scale studies that assess the distribution of C. burnetii genotypes across different geographical areas, hosts, and sources., (© 2023. The Author(s).)

Background and Aims: Telehealth has emerged as an important mode of cirrhosis care delivery, but its use and satisfaction among vulnerable populations (eg, racial/ethnic minorities, socioeconomically disadvantaged, substance use disorders) are unknown. We evaluated digital capacity, telehealth use, satisfaction and associated factors among patients receiving hepatology care via telehealth (telehepatology) across 2 Veterans Affairs and 1 safety-net Healthcare systems., Methods: English- and Spanish-speaking adults with cirrhosis (N = 256) completed surveys on telehealth use and satisfaction, quality of life, pandemic stress, alcohol use and depression. Logistic regression analyses assessed telehealth use and general linear models evaluated telehealth satisfaction., Results: The mean age was 64.5 years, 80.9% were male and 35.9% Latino; 44.5% had alcohol-associated cirrhosis; 20.8% had decompensated cirrhosis; 100% had digital (phone/computer) capacity; and 75.0% used telehepatology in the prior 6 months. On multivariable analysis, participants with alcohol-associated (vs not) cirrhosis were less likely and those with greater pandemic stress were more likely to use telehepatology (odds ratio = 0.46 and 1.41, respectively; P < .05). Better quality of life was associated with higher telehepatology satisfaction and older age was associated with lower satisfaction ( β  = 0.01 and -0.01, respectively; P < .05). Latinos had higher satisfaction, but alcohol use disorder was associated with less satisfaction with telehepatology visits ( β  = 0.22 and -0.02, respectively; P  < .05)., Conclusion: Participants had high telehepatology capacity, yet demographics and alcohol-related problems influenced telehepatology use and satisfaction. Findings underscore the need for interventions to enhance patient experience with telehepatology for certain vulnerable groups including those with alcohol-associated cirrhosis in order to optimize care delivery., (© 2024 The Authors.)

Background: Canine herpesvirus 1 (CHV-1) is an important cause of death in newborn puppies and of fertility problems in adult dogs. Identification of risk factors may help to reduce infection rates and alleviate concerns for dog owners and breeders. This study was designed to screen for CHV-1 infection in bitches of breeding kennels and farms in Iran and relate this to possible risk factors., Methods: A total of 63 vaginal samples were collected from dogs in 5 breeding kennels (n = 47) and from 7 farms (n = 16). Real-time polymerase chain reaction was used to detect the CHV-1 specific glycoprotein B (gB) gene. Prevalence rates were evaluated in relation to various risk factors, including region, housing, vaccination, deworming, pregnancy, reproductive problems, number of dogs living together and hygiene conditions., Results: In total, 21 (33.3%) of 63 vaginal samples were positive for CHV-1 DNA. The prevalence rate in farms (7/16; 43.7%) was higher than in kennels (14/47; 29.7%). No association was found between CHV-1 prevalence and potential risk factors., Conclusions: CHV-1 is highly prevalent in dogs in Iranian farms and kennels. Since the CHV1 vaccine is unlicensed in Iran, effective management strategies are essential to reduce the consequences of this pathogen., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background and Aims: Predicting changes in disease activity and serological endpoints is necessary for the management of patients with chronic hepatitis B (CHB). We examined whether HBV RNA and hepatitis B core-related antigen (HBcrAg), two specialized virological markers proposed to reflect the activity of covalently closed circular DNA, may improve the ability to predict not sustained inactive carrier phase, spontaneous alanine aminotransferase (ALT) flare, HBeAg loss, and HBsAg loss., Approach and Results: Among eligible participants enrolled in the North American Hepatitis B Research Network Adult Cohort Study, we evaluated demographic, clinical, and virologic characteristics, including HBV RNA and HBcrAg, to predict not sustained inactive carrier phase, ALT flare, HBeAg loss, and HBsAg loss through a series of Cox proportional hazard or logistic regression models, controlling for antiviral therapy use. Among the study population, 54/103 participants experienced not sustained inactive carrier phase, 41/1006 had a spontaneous ALT flare, 83/250 lost HBeAg, and 54/1127 lost HBsAg. HBV RNA or HBcrAg were predictive of all 4 events. However, their addition to models of the readily available host (age, sex, race/ethnicity), clinical (ALT, use of antiviral therapy), and viral factors (HBV DNA), which had acceptable-excellent accuracy (e.g., AUC = 0.72 for ALT flare, 0.92 for HBeAg loss, and 0.91 for HBsAg loss), provided only small improvements in predictive ability., Conclusion: Given the high predictive ability of readily available markers, HBcrAg and HBV RNA have a limited role in improving the prediction of key serologic and clinical events in patients with CHB., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: The rapid growth of Qatar in the last two decades has attracted a large influx of immigrant craft and manual workers (CMWs) seeking employment in jobs associated with food handling, domestic service, and construction. Nearly 60 % of Qatar's population are expatriates CMWs, including many from hyperendemic countries for HEV. Thus, estimating the seroprevalence of HEV in Qatar and understanding its epidemiology is essential for public health efforts to control HEV transmission in Qatar., Methods: Blood samples from 2670 CMWs were collected between 2020 and 2021. All samples were tested for HEV-IgG antibodies. Positive HEV-IgG samples were tested for HEV-IgM antibodies, and those positives were also tested for viral antigens using an HEV-Ag ELISA kit and HEV-RNA by RT-PCR to confirm current HEV infections., Results: The seroprevalence of HEV-IgG was 27.3 % (729/2670; 95 % CI: 25.6-29.0). Of those HEV-IgG positive, 8.23 % (60/729; 95 % CI: 6.30-10.5) were HEV-IgM positive. Of the IgM-positive samples, 2 were HEV-RNA positive (3.39 %; 95 % CI: 0.40-11.7), and 1 was HEV-Ag positive (1.69 %; 95 % CI: 0.04-9.09). In addition, HEV-IgG seroprevalence was associated with age and nationality, with the highest seroprevalence in participants from Egypt (IgG 60.0 %; IgM 5.56 %), Pakistan (IgG 59.0 %; IgM 2.24 %), Nepal (IgG 29.3 %; IgM 2.70 %), Bangladesh (IgG 27.8 %; IgM 2.45 %), and India (IgG 23.9 %; IgM 2.43 %)., Conclusion: In this study, we showed that the seroprevalence of HEV among CMWs was slightly higher than what was previously reported among the urban population in Qatar (2013-2016)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dmitri Litvinov has patent licensed to FemtoMag, Inc. Corresponding author is an associate editor at Heliyon-Infectious Disease Journal. GKN., (© 2023 The Authors.)

Purpose: To examine the strains in the collar area of implants supporting a cantilevered cross-arch bar prosthesis during vertical load application., Materials and Methods: A milled cross-arch metal framework supported by four implants in a trapezoidal design was supported in polymethylmethacrylate. T-strain gage rosettes were attached to the crestal areas of the implants with two grids, one recording circumference strain of the crestal area of the implant and the second recording vertical strain, torquing strains of the implant. The framework was subject to vertical loading from an MTS 810 mechanical system. Loading sites were directly on anterior and posterior implants, and on a cantilever at 7.5, 15, 22.5, and 30 mm (0.5, 1.0, 1.5, and 2.0 of the anterior-posterior spread) distal from the posterior implant on the right side. The anterior-posterior (A-P) spread from anterior to posterior implants was 15 mm. Sites were loaded individually with 50 and 100 N. The data from the rosettes were transferred to a desktop computer and processed using StrainSmart 5000 software., Results: Means and standard deviations were calculated for the 10 trials at each of the loading sites. Two-way ANOVAs were done separately for each dependent variable, the vertical grid, and the circumferential grid. The independent variables were the load magnitude and the load site. Tukey's test was used to compare groups post hoc. When directly loading the implants, loading the anterior implant resulted initially in compression followed by increasing tensile strain with 100 N loads. Loading the implant adjacent to cantilever (the posterior implant) resulted in greater strain at the collar than that observed with anterior implant with minimal bending strains. When loading the cantilever, anterior implant showed increasing bending strain at greater cantilever length, whereas the circumferential strains were greater for the supporting implant adjacent to the cantilever, particularly at 100 N loads, p ≤ 0.001., Conclusions: Limiting cantilever lengths to A-P spread ratios of 0.5 are preferred. Ratios greater than 1.0 should be avoided as flexing of the collar may occur. The dimensions of the implant, particularly wall thickness, adjacent to the cantilever should be carefully considered when planning the cantilevered implant-supported prosthesis., (© 2023 by the American College of Prosthodontists.)

Purpose: To evaluate and compare the perceived autonomy of people using wheeled mobility assistive devices (WMADs) in five community-based environments. To evaluate how personal, environmental, and assistive device-related factors impact the perceived autonomy of WMAD users., Method: A study-specific questionnaire was used to evaluate perceived satisfaction of WMAD users with their autonomy in five environments: the Home Environment, Buildings Outside of the Home Environment, Outdoor Built Environment, Outdoor Natural Environment, and Transportation. For each environment, participants rated their satisfaction with autonomy about 15 personal, environmental, and assistive device-related factors. Qualitative perceptions were also collected with open-ended questions., Results: Participants included 123 full- and part-time community-dwelling WMAD users. Participants' overall satisfaction with autonomy in the Outdoor Natural Environment was statistically significantly lower compared to the other four environments ( p  < 0.05). In all environments, the top factor respondents were most satisfied with was WMAD ease of use. Their least satisfaction was when negotiating stairs, curbs, or obstacles in the Home, Buildings Outside of the Home, and the Outdoor Built Environments. In the Outdoor Natural Environment, the most dissatisfaction was with manoeuvring on different terrains. Responses to open-ended questions supported the quantitative findings and highlighted the effects of various factors on autonomy (e.g., subject-environment familiarity)., Conclusions: WMAD users reported the greatest restriction to their autonomy in outdoor environments. Different context-specific factors were found to impact autonomy in different environments. Understanding how environment-specific contextual factors contribute to overall perception of autonomy may inform the development of future strategies to overcome identified limitations and challenges.Implications for RehabilitationWheeled mobility assistive device (WMAD) users experienced the highest autonomy in their home environments, specifically, when having access to home modification services.WMAD users had the lowest autonomy in the outdoor natural environment, with manoeuvrability on different terrains being the main predictor of the overall satisfaction with autonomy in this environment.Environment-specific contextual factors with significant impacts on perceived autonomy were identified that can inform the design and development of future WMADs (e.g., distance travelled, safety).

Primary immunodeficiencies are a diverse group of rare genetic disorders, among which phagocytic dysfunction impairs neutrophil function in a wide range of inherited disorders. Due to the heterogeneity of the disorders a multidisciplinary approach is often required for early diagnosis and initiation of appropriate treatments. The aim of this study was to evaluate the imaging findings in children admitted with phagocytic primary immunodeficiencies. Thirty-five children who fulfilled the inclusion criteria for phagocytic dysfunction were enrolled in this study. The patients were under close observation and monitoring from January 2011 until data locking in December 2017. The diagnosis of phagocytic immunodeficiency was confirmed by the patient's clinical course, presentation features, and laboratory data.  Among the 35 patients studied, the most frequent condition was chronic granulomatous disease (CGD) (23 patients), followed by different types of neutropenia (8 patients) and Job's syndrome (4 patients). Mediastinal and hilar lymphadenopathies and consolidation were the most frequent presentations. There was a significant relationship between mediastinal/hilar lymphadenopathies and fungal infections. A meaningful relationship was also found between pulmonary nodules without halo signs in patients with concomitant tuberculosis and fungal infections. A significant correlation was found between CGD, pulmonary fibrotic changes, and mediastinal lymphadenopathies. The most frequent radiological manifestations in children included mediastinal and hilar consolidations. Physicians' awareness of the radiological and clinical manifestations of these inherited diseases may be helpful in the early diagnosis and timely initiation of specific prophylaxis measures to prevent infections and also to initiate hematopoietic stem cell transplantation as the curative management modality.

Background: Biosensor technologies have been proposed as a solution to provide recognition and facilitate earlier responses to unwitnessed out-of-hospital cardiac arrest (OHCA) cases. We sought to estimate the effect of recognition on survival and modelled the potential incremental impact of increased recognition of unwitnessed cases on survival to hospital discharge, to demonstrate the potential benefit of biosensor technologies., Methods: We included cases from the British Columbia Cardiac Arrest Registry (2019-2020), which includes Emergency Medical Services (EMS)-assessed OHCAs. We excluded cases that would not have benefitted from early recognition (EMS-witnessed, terminal illness, or do-not-resuscitate). Using a mediation analysis, we estimated the relative benefits on survival of a witness recognizing vs. intervening in an OHCA; and estimated the expected additional number of survivors resulting from increasing recognition alone using a bootstrap logistic regression framework., Results: Of 13,655 EMS-assessed cases, 11,412 were included (6314 EMS-treated, 5098 EMS-untreated). Survival to hospital discharge was 191/8879 (2.2%) in unwitnessed cases and 429/2533 (17%) in bystander-witnessed cases. Of the total effect attributable to a bystander witness, recognition accounted for 84% (95% CI: 72, 86) of the benefit. If all previously unwitnessed cases had been bystander witnessed, we would expect 1198 additional survivors. If these cases had been recognized, but no interventions performed, we would expect 912 additional survivors., Conclusion: Unwitnessed OHCA account for the majority of OHCAs, yet survival is dismal. Methods to improve recognition, such as with biosensor technologies, may lead to substantial improvements in overall survival., 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 B.V. All rights reserved.)

Background: It has been suggested that nutrition might contribute to multiple sclerosis etiology (MS). Aim: This case-control study aimed to determine the role of food habits and dietary patterns in preventing or developing MS in a multicenter study in Iran (Tehran and Shiraz). Methods: In this study, food intake of (106 patients with relapsing/remitting MS (RRMS) and 72 healthy controls in Tehran) and (75 patients with relapsing/remitting MS (RRMS) and 72 healthy controls in Shiraz) were collected using a validated semi-quantitative food frequency questionnaire. Dietary patterns were extracted using factor analysis. The association between dietary patterns and the risk of MS was analyzed by Logistic regression. Results: Two major dietary patterns were extracted: the "healthy" and the "unhealthy" patterns. After adjustment for potential confounders, in Tehran city, subjects in the highest tertile of the unhealthy dietary pattern score had greater odds of having MS, compared with those in the lowest tertile (OR: 2.16; 95% CI: [1.95-2.41]; p for trend  =  0.01). In Shiraz city, subjects in the highest tertile of the unhealthy dietary pattern score had greater odds with MS than those in the lowest tertile (OR: 3.08; 95% CI: [1.27-7.38]; p for trend  =  0.01). However, in both groups, no significant association was found between healthy dietary pattern and MS risk. Conclusions: Adherence to unhealthy dietary pattern may increase the risk of MS in Iran. The results can be used for developing interventions that aim to promote healthy eating for preventing MS.

Introduction: Tissue engineering is a revolutionized biotechnology that utilizes biomaterials in regenerative medicine. Nowadays, there is a trend in employing autologous-based materials in aesthetic medicine. In this review, we discuss safety and efficacy of autologous-based fillers in the fields of aesthetic dermatology, and describe the details of preparation and injection methods based on current literature., Evidence Acqusition: PubMed, Scopus, Web of science, Embase and Google scholar were searched for studies which evaluated efficacy of autologous-based filler in the field of aesthetic dermatology from January 2000 until August 2022. Nineteen articles including five randomized clinical trials, ten prospective and four retrospective studies were selected for this review., Evidence Synthesis: Most of the studies evaluated use of biofillers in rejuvenation (twelve articles) and the remaining were in atrophic scars (six articles) and striae distensae (one article). Adjuvant treatments included liquid platelet rich growth factor (PRGF), autologous cultured fibroblast, adipose tissue micrograft, microneedling, fractional carbon dioxide laser and subcision. Application of biofillers is a safe alternative therapeutic option for soft tissue augmentation., Conclusions: Application of biofillers is especially recommended in patients who seek low-cost rejuvenation methods and those with a past history of granulomatous reactions to the other fillers. It provides the advantage of immediate filling effects with long-lasting efficacy.

Objectives: Thiopurine prodrugs are commonly used in kidney transplant recipients. Inosine triphosphate pyrophosphatase is an enzyme encoded by the ITPA gene. Alteration of ITPA gene is one of the pharmacogenetic sequence variants possibly involved in thiopurine metabolism. The ITPA 94C>A sequence variant (C-to-A substitution at nucleotide 94) is associated with an increased risk of adverse drug reactions in patients treated with the thiopurine drug. The aim of the present study was to investigate the effect of the ITPA 94C>A gene sequence variant in kidney transplant recipients., Materials and Methods: The genotyping of the ITPA rs1127354 variant was performed by the polymerase chain reaction restriction fragment length polymorphism method in 140 kidney transplant recipients and in 100 control participants. Data were analyzed with SPSS statistical software., Results: The results revealed a significant difference between control and nonrejection groups regarding the rs1127354 genotype and allele frequency. No significant difference was found between the rejection and nonrejection groups regarding the rs1127354 genotype and allele frequency. Also, a significant association was observed between the ageofthe control group and age of the rejection group. No significant differences between sex and underlying disease in patients with or without rejection were observed., Conclusions: We observed no significant differences between rejection and nonrejection transplant. Further studies are recommended, in a larger population and with different ethnicities.

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co-infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well-established) differs between HBV-HIV co-infection vs. HBV mono-infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV-HIV Ancillary Study and 105 participants in the HBRN mono-infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p < .05) in the HBV-HIV versus the HBV-only sample (HBeAg: 1.05 vs. 0.51 log 10 IU/mL; HBsAg: 3.85 vs. 3.17 log 10 IU/mL; HBV RNA: 5.60 vs. 3.70 log 10 U/mL; HBcrAg: 6.59 vs. 5.51 log 10 U/mL). Conversely, among HBeAg(-) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log 10 U/mL) were lower (p < .05) in HBV-HIV vs. HBV-only; HBcrAg levels were similar (4.14 vs. 3.64 log 10 U/mL; p = .27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co-infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status., (© 2023 John Wiley & Sons Ltd.)

Familial hypercholesterolemia (FH) is a globally underdiagnosed genetic condition associated with premature cardiovascular death. The genetic etiology data on Arab FH patients is scarce. Therefore, this study aimed to identify the genetic basis of FH in a Saudi family using whole exome sequencing (WES) and multidimensional bioinformatic analysis. Our WES findings revealed a rare heterozygous gain-of-function variant (R496W) in the exon 9 of the PCSK9 gene as a causal factor for FH in this family. This variant was absent in healthy relatives of the proband and 200 healthy normolipidemic controls from Saudi Arabia. Furthermore, this variant has not been previously reported in various regional and global population genomic variant databases. Interestingly, this variant is classified as "likely pathogenic" (PP5) based on the variant interpretation guidelines of the American College of Medical Genetics (ACMG). Computational functional characterization suggested that this variant could destabilize the native PCSK9 protein and alter its secondary and tertiary structural features. In addition, this variant was predicted to negatively influence its ligand-binding ability with LDLR and Alirocumab antibody molecules. This rare PCSK9 (R496W) variant is likely to expand our understanding of the genetic basis of FH in Saudi Arabia. This study also provides computational structural insights into the genotype-protein phenotype relationship of PCSK9 pathogenic variants and contributes to the development of personalized medicine for FH patients in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shaik, Al-Shehri, Athar, Awan, Khalili, Al Mahadi, Hejazy, Saadah, Al-Harthi, Elango, Banaganapalli, Alefishat and Awan.)

Purpose: The study had three main objectives. (1) To investigate the perceived impact of power-assist devices (PADs) on manual wheelchair (MWC) user mobility. (2) To compare perceptions about different types of PADs. (3) To identify preferred features and design characteristics of PADs., Methods: Semi-structured interviews were conducted with community-dwelling MWC users aged 31 years and older, with at least 2.5 years of experience using an MWC independently ( n  = 16). Data were thematically analysed using an inductive approach., Results: Two main themes related to participants' perceptions about the effects of PAD use were identified: (1) "Expanding my world", which illustrated the perceived benefits of using PADs (e.g., gaining a sense of autonomy and access to new environments, maintaining physical health) and (2) "Falling short", which described challenges with PADs (e.g., safety, reliability and portability issues). Participants also identified strengths and limitations of different types of PADs that were mainly related to specific user-device and device-environment interactions as well as various functional characteristics. Moreover, participants outlined their priorities for future PAD design, including improving controllability, customizability and affordability of these devices., Conclusions: Participants' perceptions about PADs varied across different types of devices and in different contexts. However, PADs were generally perceived as enhancing the capabilities of MWCs. Our findings provide insight into the factors that can be considered when selecting a PAD and can inform the development of future PADs that are better equipped to overcome challenges that MWC users frequently encounter.Implications for RehabilitationPower-assist devices (PADs) for manual wheelchairs (MWCs) have the potential to improve the mobility, community participation and well-being of users.Some of the existing PADs have safety and reliability issues that affect their performance and limit their use by MWC users.The three types of PADs (front-mounted attachments, rear-mounted attachments, powered wheels) offer different types of assistance that can benefit users with various capabilities.

Introduction: Hepatitis B surface antigen (HBsAg) loss is associated with improved long-term outcomes of patients with chronic hepatitis B but is infrequently achieved with current monotherapies. We assessed whether combination strategies that included treatment withdrawal enhanced HBsAg loss., Methods: A randomized (1:1) trial of tenofovir disoproxil fumarate (TDF) for 192 weeks with or without peginterferon (PegIFN) alfa-2a for the first 24 weeks, followed by withdrawal of TDF at week 192 with 48 weeks of off-treatment follow-up to week 240. The primary end point was HBsAg loss at week 240., Results: Of 201 participants (52% HBeAg positive, 12%/6% genotype A/A2, 7% cirrhosis) randomized to TDF + PegIFN (n = 102) or TDF alone (n = 99), 6 participants had lost HBsAg at the end of the treatment phase (week 192), 5 (5.3%) in the combination group, and 1 (1.0%) in the TDF alone group ( P = 0.09). By week 240, 9 participants had cleared HBsAg, 5.3% in combination, and 4.1% in monotherapy arms ( P = 0.73). HBsAg decline and loss occurred earlier with TDF + PegIFN than TDF, with a ≥1-logIU/mL qHBsAg decline by week 24 in 28% in TDF + PegIFN compared with 6% in TDF ( P = 0.04). HBsAg loss occurred in 7 of 12 (58%) with hepatitis B virus subgenotype A2 (all HBeAg positive) compared with only 2 of 189 (1%) with other hepatitis B virus genotypes and in 8 of 93 (8.6%) HBeAg positive vs 1 of 87 (1.1%) HBeAg negative., Discussion: PegIFN combined TDF followed by protocolized TDF withdrawal led to earlier but not higher percentages of HBsAg clearance. Pretreatment HBeAg positivity and subgenotype A2 were strongly associated with HBsAg clearance., (Copyright © 2022 by The American College of Gastroenterology.)

Introduction: Withdrawal of nucleos(t)ide analog therapy is increasingly being evaluated in chronic hepatitis B infection as a strategy to induce hepatitis B surface antigen (HBsAg) loss. The Hepatitis B Research Network Immune-Active Trial evaluated treatment with tenofovir (TDF) for 4 years ± an initial 6 months of peginterferon-α (PegIFN) (NCT01369212) after which treatment was withdrawn., Methods: Eligible participants (hepatitis B e antigen [HBeAg]-/anti-HBe+, hepatitis B virus [HBV] DNA <10 3 IU/mL, no cirrhosis) who discontinued TDF were followed for at least 1 year with optional follow-up thereafter. Retreatment was based on predefined criteria., Results: Among 201 participants who received 4 years of treatment, 97 participants (45 TDF and 52 TDF + PegIFN arm, 79 Asian) discontinued TDF. HBsAg loss occurred in 5 participants, 2 within 25 weeks and 3 within 89-119 weeks postwithdrawal (cumulative rate 4.3% by 2 years). Alanine aminotransferase (ALT) flares (>5× upper limit of normal) after TDF withdrawal occurred in 36 (37.1%) participants and occurred more frequently and earlier in those HBeAg- compared with HBeAg+ at treatment initiation. ALT flares were associated with older age and higher HBV DNA pretreatment and at the visit before the flare. ALT flares were not significantly associated with HBsAg decline or loss but were associated with immune active disease at 1 year (70.6% vs 11.9%, P < 0.0001) and 2 years (66.7% vs 25.9%, P = 0.03) postwithdrawal. Treatment reinitiation was required in 13 (13.4%) participants, and 13 others remained in a sustained inactive carrier state by the end of the study follow-up. No criteria reliably predicted safe treatment withdrawal., Discussion: Results from this trial do not support TDF withdrawal as a therapeutic strategy. HBsAg loss was infrequent within 2 years of stopping long-term TDF. If withdrawal is considered, HBV DNA should be carefully monitored with reinitiation of therapy if levels rise above 4 log 10 IU/mL to reduce the risk of ALT flares, as they were not associated with subsequent HBsAg decline or loss., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Growing evidence strongly indicates pivotal roles of gender differences in the occurrence and survival rate of patients with bladder cancer, with a higher incidence in males and poorer prognosis in females. Nevertheless, the molecular basis underlying gender-specific differences in bladder cancer remains unknown. The current study has tried to detect key genes contributing to gender differences in bladder cancer patients., Materials and Methods: The gene expression profile of GSE13507 was firstly obtained from the Gene Expression Omnibus (GEO) database. Further, differentially expressed genes (DEGs) were screened between males and females using R software. Protein-protein interactive (PPI) network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Kaplan-Meier survival analyses were also performed., Results: We detected six hub genes contributing to gender differences in bladder cancer patients, containing IGF2, CCL5, ASPM, CDC20, BUB1B, and CCNB1. Our analyses demonstrated that CCNB1 and BUB1B were upregulated in tumor tissues of female subjects with bladder cancer. Other genes, such as IGF2 and CCL5, were associated with a poor outcome in male patients with bladder cancer. Additionally, three signaling pathways (focal adhesion, rheumatoid arthritis, and human T-cell leukemia virus infection) were identified to be differentially downregulated in bladder cancer versus normal samples in both genders., Conclusion: Our findings suggested that gender differences may modulate the expression of key genes that contributed to bladder cancer occurrence and prognosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

Regarding the important role of the urease enzyme as a virulence factor in urease-positive microorganisms in this study, new series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives were designed and synthesized. All compounds evaluated against urease enzyme exhibiting IC 50 values of 0.87 ± 0.09 to 8.32 ± 1.21 µM as compared with thiourea as the positive control (IC 50  = 22.54 ± 2.34 µM). The kinetic evaluations of 6a as the most potent derivative recorded a competitive type of inhibition. Molecular dynamic simulations of the 6a derivative were also conducted, showing that 6a occupied the active site with closed state. Antimicrobial activities of all derivatives were performed, and 6f (R = 3-Cl), 6g (R = 4-Cl), and 6h (R = 3,4-diCl) analogs demonstrated significant antifungal activities with MIC values of 1, 2, and 0.5 µg/mL compared with fluconazole with MIC = 2 µg/mL. Synthesized analogs also exhibited potent urease inhibitory activities against C. neoformans (IC 50  = 83.7-118.7 µg/mL) and P. mirabilis (IC 50  = 74.5-113.7 µg/mL), confirming their urease inhibitory potential. The results demonstrated that the designed scaffold could be considered a suitable pharmacophore to develop potent urease inhibitors., (© 2023. The Author(s).)

Objectives: Adherence to lifestyle modification (diet, exercise, and alcohol cessation) for fatty liver disease (FLD) management remains challenging. The study examined stigma, barriers, and factors associated with motivation to adhere to lifestyle modification in a diverse and vulnerable population with FLD., Methods: From 2/19/2020 to 2/28/2022, 249 FLD patients within San Francisco safety-net hepatology clinics were surveyed along with clinical data taken from medical records. Multivariable modeling assessed factors associated with motivation to adhere to lifestyle modification in a cross-sectional study., Results: Median age was 53 years, 59% female, 59% Hispanic, 25% Asian/Pacific Islander, 9% White, and 2% Black, 79% were non-English speakers, 64% had ≤ high school education, and 82% reported <$30,000 annual income. Common comorbidities included hyperlipidemia (47%), hypertension (42%), diabetes (39%), and heavy alcohol use (22%). Majority (78%) reported experiencing stigma, 41% reported extreme motivation, and 58% reported ≥ two barriers. When controlling for age, sex, Hispanic ethnicity, alcohol consumption, BMI, >high school (coef 1.41, 95% CI 0.34-2.48), stigma (coef 0.34, 95% CI 0.07-0.62), and depression (coef -1.52, 95% CI -2.79 to -0.26) were associated with motivation., Conclusions: Stigma is commonly reported among FLD patients. Interventions to enhance patient education and mental health support are critical to FLD management, especially in vulnerable populations., Competing Interests: Sheyla P. Medina, Rebecca G. Kim, Catherine Magee and Noah Stapper do not have any disclosures relevant to this manuscript., (© 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background: Quality of life and marital satisfaction are important components of reproductive-age women's health. This study aimed to compare the quality of life and marital satisfaction in women of reproductive age in Iran and Afghanistan before and after the COVID-19 pandemic., Methods: This was a cross-sectional study on a sample of Iranian and Afghan women of reproductive age. To collect the data, the 12-item short-form health survey (SF-12) and the Enrich marital satisfaction scale were used to assess the quality of life and marital satisfaction, respectively. In addition, the Global Rating of Change (GRC) was used in order to evaluate the quality of life and marital satisfaction compared to before the COVID-19 pandemic. Data were evaluated descriptively through statistics including sing t-test, and chi-square, Logistic regression was performed to assess the relationship between outcome variables and independent variables., Results: In all 599 reproductive-age women (300 Iranian, and 299 Afghan) were studied. After adjusting for demographic variables, no significant difference was observed between the two groups for the physical component (P = 0.05) and mental component summary scores of quality of life (P = 0.166) as measured by the SF-12. The majority of Iranian women reported that their quality of life was worsened compared to before the pandemic (57.2%), while in the Afghan group, a higher percentage declared that it was unchanged (58.9%). The mental component of quality of life had no significant relationship with any of the independent variables including nationality. In contrast, the physical component quality of life had a significant relationship with nationality (P = 0.01). Iranian women had more marital satisfaction than Afghan women (P<0.001) and marital satisfaction had a significant relationship with nationality (P<0.001). Most women in both groups (70% of Iranian and 60% of Afghan women) declared that their marital satisfaction unchanged compared to before the COVID-19 pandemic., Conclusion: The results showed that the quality of life of Iranian and Afghan women of reproductive age was almost the same before and after the pandemic. However, Iranians scored lower on the mental component summary and Afghans reported lower scores on the physical component summary. Marital satisfaction of Afghan women was much lower than that of Iranian women. The findings suggest the need for serious attention by health care authorities. Providing a supportive environment might be considered a primary step towards a better quality of life for these populations., (© 2023. The Author(s).)

Multiple sclerosis (MS) is a progressive inflammatory neurodegenerative disease of the nervous system accompanied by demyelination. MS-associated cognitive impairments mainly involve recent memory, information processing speed, stable memory, and executive function. Moreover, MS is associated with impaired glucose and insulin metabolism, which can exacerbate cognitive decline. The present study aimed to compare the cognitive status of MS patients with and without insulin resistance. In this cross-sectional study, 74 relapsing-remitting multiple sclerosis diagnosed patients were enrolled. Indicators of insulin resistance, including fasting blood glucose, insulin level, and homeostatic model assessment of insulin resistance (HOMA-IR) index, were measured. They were then divided into two groups based on the results of the HOMA-IR index. Cognition status was evaluated by the minimal assessment of cognitive function in multiple sclerosis battery. The prevalence of insulin resistance was 37.8%, and the prevalence of cognitive decline was estimated to be 67.56%. Mean scores of the California verbal learning test (CVLT), CVLT delayed free recall, controlled oral word association test, and judgment of line orientation tests were significantly lower in MS patients with insulin resistance than without. In addition, a negative correlation was demonstrated between the results of the CVLT, CVLT delayed free recall, controlled oral word association test, judgment of line orientation tests, brief visuospatial memory test, and Delis-Kaplan executive function system sorting tests and fasting insulin levels. Greater verbal memory and spatial comprehension impairments were observed in MS patients with insulin resistance., (© 2023 British Society for Neuroendocrinology.)

Background & Aims: Most patients in the immunotolerant (IT) phase of chronic hepatitis B (CHB) transition to the immune active (IA-hepatitis B surface antigen [HBeAg]+) phase by early adulthood. We examined characteristics of adults in the IT vs IA-HBeAg+ phase and rate of transition from IT to other phases of CHB, with a focus on those ≥40 years., Methods: Demographic, clinical, and virologic characteristics of participants in the Hepatitis B Research Network adult cohort study with IT CHB (alanine aminotransferase ≤1.5 × upper limit of normal, hepatitis B virus DNA >10 7 IU/mL) were compared by age category, and to those with IA-HBeAg+ CHB in cross-sectional analysis. This study received institutional review board approval at all participating centers., Results: Of 107 adult IT participants, 52 (48%) were <30, 33 (31%) were 30 to 39, and 22 (21%) were ≥40 years old (maximum, 71 years). Among IT groups, the proportion born in Asia and duration of CHB were greater in older IT groups, but virologic and liver disease characteristics were similar. Compared with IA-HBeAg+ participants (n = 192), IT participants were younger, fewer were men, more were Asian, and platelets, qHBsAg, and qHBeAg levels were higher. Similar differences were observed when comparisons were made with the ≥40 years IT group. Among IT participants, 60 (56%) transitioned during 206 person-years of follow-up. The phase transition rate per 100 person-years was highest in the <30 years group (33.0 [95% confidence interval [CI], 23.4-46.7]) vs the 30 to 39 years group (24.8 [95% CI, 15.6-39.4]) and ≥40 group (27.4 [95% CI, 14.8-50.9]), but 95% CIs overlapped., Conclusions: In a large North American population, over 50% of adults in the IT phase of CHB were ≥30 years and 20% were ≥40 years old, but older IT patients had similar characteristics and rates of transition as younger IT patients., (Copyright © 2023. Published by Elsevier Inc.)

Background: Maternal mortality is an indication of the health status of women in the society., Aims: To investigate the maternal mortality ratio, causes of maternal mortality, and related risk factors among Iranian women., Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and the Peer Review of Electronic Search Strategies (PRESS) guideline, we systematically searched electronic databases, and the grey literature, for publications in Farsi and English from 1970 to January 2022 for studies that reported the number of maternal deaths and/or maternal mortality ratio and their related factors. Data analysis was conducted using Stata 16 and 2-sided P ≤ 0.05 was considered statistically significant, if not otherwise specified., Results: A subgroup meta-analysis of studies conducted since 2000 estimated the maternal mortality ratio as 45.03 per 100 000 births during 2000-2004, 36.05 during 2005-2009, and 23.71 after 2010. The most frequent risk factors for maternal mortality were caesarean section, poor antenatal and delivery care, unskilled birth attendance, age, low maternal education level, lower human development index, and residence in rural or remote areas., Conclusion: There has been a significant decrease in maternal mortality in the Islamic Republic of Iran during the last few decades. Mothers in the country need to be monitored more carefully by trained healthcare workers during the pregnancy, delivery and postpartum periods so they can effectively handle postpartum complications, such as haemorrhage and infection, thereby further reducing maternal mortality., (Copyright © Authors 2023; Licensee: World Health Organization. EMHJ is an open access journal. This paper is available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

The advances in high-throughput sequencing (HTS) technologies and bioinformatic tools have provided new opportunities for virus and viroid discovery and diagnostics. Hence, new sequences of viral origin are being discovered and published at a previously unseen rate. Therefore, a collective effort was undertaken to write and propose a framework for prioritizing the biological characterization steps needed after discovering a new plant virus to evaluate its impact at different levels. Even though the proposed approach was widely used, a revision of these guidelines was prepared to consider virus discovery and characterization trends and integrate novel approaches and tools recently published or under development. This updated framework is more adapted to the current rate of virus discovery and provides an improved prioritization for filling knowledge and data gaps. It consists of four distinct steps adapted to include a multi-stakeholder feedback loop. Key improvements include better prioritization and organization of the various steps, earlier data sharing among researchers and involved stakeholders, public database screening, and exploitation of genomic information to predict biological properties., Competing Interests: AF was employed by Fera Science Ltd. AyM and YH were employed by Abiopep S.L. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fontdevila, Khalili, Maachi, Rivarez, Rollin, Salavert, Temple, Aranda, Boonham, Botermans, Candresse, Fox, Hernando, Kutnjak, Marais, Petter, Ravnikar, Selmi, Tahzima, Trontin, Wetzel and Massart.)

Background: Healthcare-associated infections (HAIs) are among the most critical challenges for patients and healthcare providers. To achieve the goals of the surveillance system, it is necessary to identify its barriers and problems. This study aimed to identify the barriers and problems of the surveillance system for HAIs., Methods: This qualitative study was conducted using the content analysis method to investigate the challenges of this surveillance system from the perspective of 18 infection control nurses from hospitals in different cities of Iran with work experience of 1 to 15 years. Data were collected through semi-structured interviews and analyzed using the Lundman and Graneheim qualitative content analysis method., Results: In this study, we found 2 categories and 7 subcategories. Two categories were barriers related to human resources and organizational barriers to infection control. The 7 subcategories included weakness of medical staff in adherence to health principles, obstacles related to patients, high workload and insufficient motivation, lack of staff knowledge, lack of human resources, functional and logistical weaknesses, and weaknesses in the surveillance system., Conclusion: To reduce problems and improve HAIs reporting, the HAIs surveillance system needs the support of health system officials and managers. This administrative and support focus can establish the framework for removing and lowering other barriers, such as the number of reported cases, physician and staff noncooperation, and the prevalence of HAIs. It can also bring HAIs cases closer to reality., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

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

Background: The physiological level of reactive oxygen species (ROS) is necessary for many cellular functions. However, during the in-vitro manipulations, cells face a high level of ROS, leading to reduced cell quality. Preventing this abnormal ROS level is a challenging task. Hence, here we evaluated the effect of sodium selenite supplementation on the antioxidant potential, stemness capacity, and differentiation of rat-derived Bone Marrow MSCs (rBM-MSCs) and planned to check our hypothesis on the molecular pathways and networks linked to sodium selenite's antioxidant properties., Methods: MTT assay was used to assess the rBM-MSCs cells' viability following sodium selenite supplementation (concentrations of: 0.001, 0.01, 0.1, 1, 10 µM). The expression level of OCT-4, NANOG, and SIRT1 was explored using qPCR. The adipocyte differentiation capacity of MSCs was checked after Sodium Selenite treatment. The DCFH-DA assay was used to determine intracellular ROS levels. Sodium selenite-related expression of HIF-1α, GPX, SOD, TrxR, p-AKT, Nrf2, and p38 markers was determined using western blot. Significant findings were investigated by the String tool to picture the probable molecular network., Results: Media supplemented with 0.1 µM sodium selenite helped to preserve rBM-MSCs multipotency and keep their surface markers presentation; this also reduced the ROS level and improved the rBM-MSCs' antioxidant and stemness capacity. We observed enhanced viability and reduced senescence for rBM-MSCs. Moreover, sodium selenite helped in rBM-MSCs cytoprotection by regulating the expression of HIF-1 of AKT, Nrf2, SOD, GPX, and TrxR markers., Conclusions: We showed that sodium selenite could help protect MSCs during in-vitro manipulations, probably via the Nrf2 pathway., (© 2023. The Author(s).)

Utilizing both medium enrichment and a thermos-responsive substrate to maintain the cell-to-cell junctions and extracellular matrix (ECM) intact, cell sheet technology has emerged as a ground-breaking approach. Investigating the possibility of using sodium selenite (as medium supplementation) and PCL-PEG-PCL (as vessel coating substrate) in the formation of the sheets from rat bone marrow-derived mesenchymal stem cells (rBMSCs) was the main goal of the present study. To this end, first, Polycaprolactone-co-Poly (ethylene glycol)-co-Polycaprolactone triblock copolymer (PCEC) was prepared by ring-opening copolymerization method and characterized by FTIR, 1  H NMR, and GPC. The sol-gel-sol phase transition temperature of the PCEC aqueous solutions with various concentrations was either measured. Next, rBMSCs were cultured on the PCEC, and let be expanded in five different media containing vitamin C (50 µg/ml), sodium selenite (0.1 µM), vitamin C and sodium selenite (50 µg/ml + 0.1 µM), Trolox, and routine medium. The proliferation of the cells exposed to each material was evaluated. Produced cell sheets were harvested from the polymer surface by temperature reduction and phenotypically analyzed via an inverted microscope, hematoxylin and eosin (H&E) staining, and field emission scanning electron microscopy (FESEM). Through the molecular level, the expression of the stemness-related genes (Sox2, Oct-4, Nanog), selenium-dependent enzymes (TRX, GPX-1), and aging regulator gene (Sirt1) were measured by q RT-PCR. Senescence in cell sheets was checked by beta-galactosidase assay. The results declared the improved ability of the rBMSCs for osteogenesis and adipogenesis in the presence of antioxidants vitamin C, sodium selenite, and Trolox in growth media. The data indicated that in the presence of vitamin C and sodium selenite, the quality of the cell sheet was risen by reducing the number of senescent cells and high transcription of the stemness genes. Monolayers produced by sodium selenite was in higher-quality than the ones produced by vitamin C., (© 2023. The Author(s).)

Importance: Disparities in treatment initiation may affect outcomes, but data on racially diverse populations with chronic hepatitis B virus (HBV) infection are limited., Objective: To examine whether HBV treatment initiation and outcomes differ among racial groups., Design, Setting, and Participants: From January 14, 2011, to January 28, 2018, hepatitis B surface antigen-positive adults (age ≥18 years) not receiving anti-HBV therapy were enrolled and followed up at weeks 12, 24, and every 24 weeks thereafter in a multicenter longitudinal cohort study (Hepatitis B Research Network [HBRN] adult cohort study) conducted in North America. The last study visit and data collection were completed January 28, 2019. Data were analyzed from August 27, 2021, to August 25, 2022. All HBRN participants were included unless they had acute HBV, HIV, hepatitis C or D, less than 24-weeks of follow-up after enrollment, initiated treatment at or immediately after enrollment, or had unknown race., Exposures: Participants had clinical and laboratory assessments and could receive anti-HBV treatment after enrollment., Main Outcomes and Measures: Hepatitis B virus treatment initiation and major adverse liver outcomes (hepatic decompensation, hepatocellular carcinoma, liver transplant, and death)., Results: Of 1550 participants, 193 (12%) were African American or Black, 1157 (75%) were Asian, 157 (10%) were White, and 43 (3%) were other races; 789 (51%) were women, and the median age was 41.2 (IQR, 32.9-51.6) years. Sociodemographic and virologic parameters differed between groups. During 5727 person-years of follow-up, 504 participants initiated treatment, with incidences of 4.8 per 100 person-years in African American or Black individuals, 9.9 per 100 person-years in Asian individuals, 6.6 per 100 person-years in White individuals, and 7.9 per 100 person-years in those of other races (P < .001). A lower proportion (14%) of African American or Black participants met treatment criteria compared with Asian (22%) and White (27%) individuals (P = .01). The cumulative probabilities of treatment initiation after meeting the criteria were not significantly different among racial groups (African American or Black, 0.45; Asian, 0.38; White, 0.40 at 48 weeks and African American or Black, 0.45; Asian, 0.51; White, 0.51 at 72 weeks; P = .68). The incidence of major adverse liver outcomes was 0.1 per 100 person-years and did not differ by race., Conclusions and Relevance: In this observational study of chronic HBV, African American or Black participants were less likely than individuals of other races to meet treatment criteria, but among those who did, HBV treatment receipt did not differ significantly by race or socioeconomic factors. Not all eligible participants initiated treatment, but adverse liver outcomes were rare. These findings may not be generalizable to patients with chronic HBV receiving care in other settings.

Background: Childhood vitiligo differs from adult vitiligo in many aspects. To the best of the authors' knowledge, there is no systematic review of different clinicoepidemiological patterns of vitiligo in children. This study aimed to review the characteristics of vitiligo among the paediatric population., Methods: In June 2022, a comprehensive search was conducted using MeSh-based keywords on online databases including PubMed, Scopus and Web of Sciences. The papers were assessed, and the eligible articles were selected. The selection of articles followed three distinct steps. The extracted clinicoepidemiological data were then imported into the STATA software for meta-analysis., Results: The meta-analysis of 17 studies with 4365 subjects yielded 2475 women (estimated=56.8%, 95% CI 54.45 to 59.22). The female-to-male ratio was determined to be 1.3:1. Meta-regression demonstrated a significant relationship between continents and gender (p=0.03). The most prevalent types of non-segmental vitiligo were vulgaris (42.49%), focal (27.21%) and acrofacial (17.8%). The pooled ratio of non-segmental to segmental was 4.6:1. The highest and lowest ratios were found in Africa with one study (estimated=11.56%, 95% CI -0.98 to 24.10) and America with two studies (estimated=3.02%, 95% CI 1.54 to 4.50), respectively. Using meta-regression, the relationship between continents and vitiligo type was found to be insignificant (p=0.47). Positive family history was recorded in 657 patients (estimated = 16.88%, 95% CI 13.37 to 20.39). Positive family history varied by country of study from 13.91% (Asia with 11 studies) to 27.01% (Europe with two studies) (p=0.11). Kobner phenomena and leukotrichia were noted in 687 (25.47%) and 461 (18.52%) patients, respectively., Conclusion: The review indicated that childhood vitiligo is more prevalent in women. Non-segmental forms of childhood vitiligo were the most common, including vulgaris, focal and acrofacial. The clinicoepidemiological pattern of childhood vitiligo is variable in different geographic areas., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study was conducted in an aircraft maintenance, repair, and overhaul (MRO) company in 2021 to identify the extent of occupational exposures and quantitative assessment of the health risk due to inhalation of chemical compounds. According to the inspection of different parts of this company, heavy metals including Co, Cd, Ni, Pb, Cr(VI), and Mn and organic compounds including benzene, toluene, ethylbenzene, xylene (BTEX), and methyl ethyl ketone (MEK) were selected for health risk assessment. In total, the air in the inhalation area of active workers was sampled in 51 workstations. Measurement of the above pollutants showed that the average occupational exposure to Cd, Pb, and all organic compounds fell within the acceptable range of occupational exposure standard, while the measured values for Co, Ni, Mn, and Cr(VI) exceeded the standard limit. According to calculations, the highest carcinogenic risk (CR) was seen in the plating (airplane) workshop for exposure to Cr(VI) (7.58E-01), and the lowest CR was observed in the electronic workshop for exposure to Pb (7.75E-08). The highest non-carcinogenic hazard (HQ) was found in the welding workshop for exposure to Co (1.00E + 04), while the lowest HQ was related to toluene in the fabrication workshop (9.10E-03). Considering the high rate of exposure indicators, CR and HQ exceeded the standards set by the American Environmental Protection Agency (EPA) in most workshops. Accordingly, company managers should take the necessary measures to reduce the vulnerability of individuals working in areas with unacceptable CR and HQ., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Central nervous system cancers (CNS cancers) impose a significant burden upon healthcare systems worldwide. Currently, the lack of a comprehensive study to assess various epidemiological indexes of CNS cancers on national and subnational scales in Iran can hamper healthcare planning and resource allocation in this regard. This study aims to fill this gap by providing estimates of CNS cancer epidemiological measures on national and subnational levels in Iran from 1990 to 2019., Materials and Methods: This study is a part of Global Burden of Disease (GBD) 2019 that contains epidemiological measures including prevalence, incidence, mortality, Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLDs), and Years of Life Lost (YLLs) of CNS cancers. Age standardization was utilized for comparing different provinces., Results: In 2019, 5811 (95% Uncertainty Interval: 2942-7046) national new cases and 3494 (1751-4173) deaths due to CNS cancers were reported. National age-standardized incidence (ASIR), deaths (ASDR), and DALYs rates were 7.3 (3.7-8.8), 4.6 (2.3-5.5), and 156.4 (82.0-187.0) per 100,000 in 2019, respectively. Subnational results revealed that ASDR and ASIR have increased in the past 30 years in all provinces. Although incidence rates have increased in all age groups and genders since 1990, death rates have remained the same for most age groups and genders except for young patients aged under 15, where a decrease in mortality and YLLs can be observed., Conclusion: The incidence, deaths, and DALYs of CNS cancers increased at national and subnational levels. These findings should be considered for planning and resource allocation., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Healthcare-associated infections (HAIs) are a threat to patients. Accurate surveillance is required to identify and prevent HAIs. To estimate the incidence rate, report the accuracy and identify the barriers of reporting HAIs using a mixed-method study., Methods: In this quantitative study, we externally evaluated the incidence rate and accuracy of the routine surveillance system in one of the main hospitals by an active follow-up of patients from September to December 2021. We used in-depth interviews with 18 experts to identify the barriers of the routine surveillance system., Results: Among 404 hospitalized patients, 88 HAIs were detected. The estimated rate of HAIs was 17.1 (95% Confidence Intervals 95: 14.1, 21.1) per 1000 patient-days follow-up. However, in the same period, 116 HAIs were reported by the routine surveillance system, but the agreement between the two approaches was low (sensitivity = 61.4%, specificity = 82.6%, negative predictive value = 89.7%, and positive predictive validity = 46.5%). The minimum and maximum positive predictive values were observed in urinary tract infection (32.3%) and surgical site infection (60.9%). The main barrier of reporting HAIs was lack of cooperation in reporting HAIs by infection control link nurses and laboratory supervisors., Conclusions: The discrepancy between the longitudinal study findings and the routine surveillance might be related to the inaccessibility of the surveillance system to clinical information of patients. In this regard, decreasing the barriers, increasing the knowledge of infection control nurses and other nurses, as well as the development of hospital information systems are necessary., (© 2023. The Author(s).)

Sudden cardiac arrest (SCA) is a leading cause of mortality worldwide. The SCA-to-resuscitation interval is a key determinant of patient outcomes, highlighting the clinical need for reliable and timely detection of SCA. Near-infrared spectroscopy (NIRS), a non-invasive optical technique, may have utility for this application. We investigated transcutaneous NIRS as a method to detect pentobarbital-induced changes during cardiac arrest in eight Yucatan miniature pigs. NIRS measurements during cardiac arrest were compared to invasively acquired carotid blood pressure and partial oxygen pressure (PO 2 ) of spinal cord tissues. We observed statistically significant decreases in mean arterial pressure (MAP) 64.68 mmHg ± 13.08, p < 0.0001), spinal cord PO 2 (38.16 mmHg ± 20.04, p = 0.0028), and NIRS-derived tissue oxygen saturation (TSI%) (14.50% ± 3.80, p < 0.0001) from baseline to 5 min after pentobarbital administration. Euthanasia-to-first change in hemodynamics for MAP and TSI (%) were similar [MAP (10.43 ± 4.73 s) vs TSI (%) (12.04 ± 1.85 s), p = 0.3714]. No significant difference was detected between NIRS and blood pressure-derived pulse rates during baseline periods (p > 0.99) and following pentobarbital administration (p = 0.97). Transcutaneous NIRS demonstrated the potential to identify rapid hemodynamic changes due to cardiac arrest in periods similar to invasive indices. We conclude that transcutaneous NIRS monitoring may present a novel, non-invasive approach for SCA detection, which warrants further investigation., (© 2023. The Author(s).)

In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC 50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC 50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors., (© 2023. The Author(s).)

In the present study, a series of aryl-substituted thioqunoline conjugated to thiosemicarbazide were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis. Among the synthesized derivatives, compound 10g bearing para-chlorophenyl moiety was proved to be the most potent tyrosinase inhibitor with an IC 50 value of 25.75 ± 0.19 µM. Compound 10g as the most potent derivative exhibited a noncompetitive inhibition pattern against tyrosinase in the kinetic study. Furthermore, the in silico cavity detection, as well as the molecular docking assessments, were performed to follow the behavior of 10g within the proposed binding site. Besides, the toxicity of 10g and its potency to reduce the melanin content on A375 cell lines were also measured. Consequently, aryl-substituted thioqunolines conjugated to thiosemicarbazide might be a promising candidate in the cosmetics, medicine, and food industry as tyrosinase inhibitors., (© 2023. The Author(s).)

The aim of the current systematic review was to gather the researches about the effect of quinoa (chenopodium quinoa) on inflammatory parameters interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). Search was performed using PubMed, Scopus, WOS, ProQuest, and Google scholar databases without any restriction on language or publication date until July 2022 and search alert services were used to detect novel papers published after the initial search. Only 20 animal and in vitro investigations were eligible for this systematic review. According to in vitro researches and 8 of 14 animal investigations, IL-6, IL-1β, and TNF-α level decreased remarkably after quinoa administration, which indicates the capability of quinoa in alleviating inflammatory factors. Quinoa is favorable but not yet a confirmed agent for alleviating systemic inflammation in inflammatory diseases., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background and Aims: Liver injury may persist in patients with HBV receiving antiviral therapy who have ongoing transcription and translation. We sought to assess ongoing HBV transcription by serum HBV RNA, translation by serum hepatitis B core related antigen (HBcrAg), and their associations with hepatic HBsAg and HBcAg staining in patients coinfected with HBV and HIV., Methods: This is a cross-sectional study of 110 adults coinfected with HBV and HIV who underwent clinical assessment and liver biopsy. Immunohistochemistry (IHC) was performed for HBsAg and HBcAg. Viral biomarkers included quantitative HBsAg, HBV RNA, and HBcrAg., Results: Participants' median age was 49 years (male, 93%; Black, 51%; HBeAg+, 65%), with suppressed HBV DNA (79%) and undetectable HIV RNA (77%) on dually active antiretroviral therapy. Overall, HBV RNA and HBcrAg were quantifiable in 81% and 83%, respectively (96% and 100% in HBeAg+, respectively). HBcAg staining was detected in 60% and HBsAg in 79%. Higher HBV RNA was associated with higher HBcAg and HBsAg IHC grades (both p < 0.0001). The HBsAg membranous staining pattern was significantly associated with higher HBV-RNA and HBcrAg levels., Conclusion: HBcAg and HBsAg IHC staining persisted despite viral suppression, and IHC grades and staining patterns correlated with markers of transcription (HBV RNA) and translation (HBcrAg). These data indicate that apparent HBV suppression is associated with residual transcription and translation that could contribute to liver pathology. Additional antiviral strategies directed to HBV protein expression may be useful to ameliorate liver injury., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Members of the genus Luteovirus are responsible for economically destructive plant diseases worldwide. Over the past few years, three luteoviruses infecting Prunus trees have been characterized. However, the biological properties, prevalence, and genetic diversity of those viruses have not yet been studied. High-throughput sequencing of samples of various wild, cultivated, and ornamental Prunus species enabled the identification of four novel species in the genus Luteovirus for which we obtained complete or nearly complete genomes. Additionally, we identified another new putative species recovered from Sequence Read Archive data. Furthermore, we conducted a survey on peach-infecting luteoviruses in eight European countries. Analyses of 350 leaf samples collected from germplasm, production orchards, and private gardens showed that peach-associated luteovirus (PaLV), nectarine stem pitting-associated virus (NSPaV), and a novel luteovirus, peach-associated luteovirus 2 (PaLV2), are present in all countries; the most prevalent virus was NSPaV, followed by PaLV. The genetic diversity of these viruses was also analyzed. Moreover, the biological indexing on GF305 peach indicator plants demonstrated that PaLV and PaLV2, like NSPaV, are transmitted by graft at relatively low rates. No clear viral symptoms have been observed in either graft-inoculated GF305 indicators or different peach tree varieties observed in an orchard. The data generated during this study provide a broader overview of the genetic diversity, geographical distribution, and prevalence of peach-infecting luteoviruses and suggest that these viruses are likely asymptomatic in peach under most circumstances.

Multiple real-world studies have confirmed the safety and efficacy of hepatitis C (HCV) direct-acting antivirals (DAAs); however, few studies have provided data on long-term outcomes of patients without cirrhosis after achieving sustained virologic response (SVR). 1-3 The aims of this analysis were to describe, among individuals in the PRIORITIZE Study achieving SVR: (1) the frequency of laboratory testing and imaging during long-term follow-up (LTFU), (2) changes in liver tests, (3) occurrence of hepatic decompensation or hepatocellular carcinoma (HCC) and deaths, and (4) durability of SVR., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus (HCV) screening remains suboptimal. We assessed the efficacy of a mobile application and provider alert in enhancing HCV screening among Asian Americans., Methods: A secondary analysis of a cluster-randomized clinical trial was performed during the birth cohort screening era to assess the efficacy of a Hepatitis App (intervention), a multilingual mobile application delivering interactive video education on viral hepatitis and creating a Provider Alert printout, at primary care clinics within 2 healthcare systems in San Francisco from 2015 to 2017. A comparison group received usual care and a similar intervention on nutrition and physical activity. The outcome was electronic health record (EHR) documentation of HCV screening along with patient-provider communication about testing and test ordering., Results: Four hundred fifty-two participants (mean age 57 years, 36% male, 80% foreign-born) were randomized by provider clusters to the intervention (n = 270) or comparison groups (n = 182). At 3-month follow up, the intervention group was more likely than the comparison group to be aware of HCV (75% vs 59%, P = .006), to discuss HCV testing with their providers (63% vs 13%, P < .001), to have HCV testing ordered (39% vs 10%, P < .001), and to have EHR-verified HCV testing (30% vs 6%, P < .001). Within the intervention group, being born between 1945 and 1965 (odds ratio, 3.15; 95% confidence interval, 1.35-7.32) was associated with increased HCV testing., Conclusions: The Hepatitis App delivered in primary care settings was effective in increasing HCV screening in a socioeconomically diverse Asian American cohort. This highlights the importance of mobile technology as a patient-centered strategy to address gaps in HCV care., Competing Interests: Potential conflicts of interest. MK's full disclosure includes research grant funding (to her institution) from Gilead Sciences, Inc. and Intercept Pharmaceuticals. She has also served on the scientific advisory boards of Gilead Sciences, Inc. TTN's spouse was formerly employed by and owns stocks in Gilead Sciences, Inc. IL is currently employed at Gilead Sciences, Inc. She did not have any industry affiliation at the time of conduct of this study. No additional assistance with manuscript preparation was received. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

To identify potent urease inhibitors, in the current study, a series of thioxothiazolidinyl-acetamides were designed and synthesized. The prepared compounds were characterized by spectroscopic techniques, including FTIR, 1 HNMR, 13 CNMR, and elemental analysis. In the enzymatic assessments, it was demonstrated that all derivatives had significant urease inhibition with IC 50 values in the range of 1.473-9.274 µM in comparison with the positive control hydroxyurea (IC 50  = 100.21 ± 2.5 µM) and thiourea (IC 50  = 23.62 ± 0.84 µM). Compound 6i (N-benzyl-3-butyl-4-oxo-2-thioxothiazolidine-5-carboxamide) was the most active agent with an IC 50 value of 1.473 µM. Additionally, kinetic investigation and in silico assessments of 6i was carried out to understand the type of inhibition and behavior of the most potent derivative within the binding site of the enzyme. Noteworthy, the anti-urease assay against P. vulgaris revealed 6e and 6i as the most active agents with IC 50 values of 15.27 ± 2.40 and 17.78 ± 3.75 µg/mL, respectively. Antimicrobial evaluations of all compounds reveal that compounds 6n and 6o were the most potent antimicrobial agents against the standard and resistant S. aureus. 6n and 6o also showed 37 and 27% inhibition in the development of biofilm by S. aureus at 512 µg/ml. Furthermore, the MTT test showed no toxicity up to 100 µM. Taken together, the study suggests that the synthesized thioxothiazolidinyl-acetamides bases derivatives may serve as potential hits as urease inhibitors., (© 2023. The Author(s).)