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The main goal of this study was to identify areas prone to groundwater exploration in the Anar-Dashtegol anticline, southwest of Iran. The fractal geometry was used to determine the linearity density in the areas. In the first step, the groundwater conditioning factors, such as distance from faults and fractures, faults and fractures density, distance from springs, spring discharge, relief, and slopes were prepared. Lineament density map was spatially prepared using fractal geometry, box-counting method. Thematic map of each parameter was prepared using geographic information system (GIS) and remote sensing data. Measuring the rate and weight of the maps was performed using the crisp method on a scale from 0 to 9 and analytical hierarchical process (AHP), respectively. The final output map showed different zones of groundwater prospective potential, which was divided into four orders: very low, low, moderate, and high. Results indicate that precipitation, faults, and relief are the most affecting factors on karst water potential at the Anar-Dashtegol anticline, and that areas with high potential are located in northern plunge. Karstic wells present in the study area have confirmed that zones with high groundwater potential identified from the study developed here are characterized by a high yield. [ABSTRACT FROM AUTHOR]

Introduction: Patients with leukemia undergoing bone marrow aspiration (BMA) frequently experience considerable pain and anxiety, which may negatively impact physiological outcomes. Reflexology, a complementary therapeutic approach, has demonstrated effectiveness in reducing pain and anxiety across various medical procedures. This randomized clinical trial aimed to evaluate the impact of foot reflexology on pain, anxiety, and physiological indices in leukemia patients undergoing BMA., Methods: This randomized clinical trial was conducted at Ayatollah Khansari Hospital in Arak between August 2021 and January 2023. Patients were randomly assigned to either a reflexology intervention group or a control group receiving routine care. The intervention group underwent a 30-min foot reflexology session. Pain was assessed using the Numeric Rating Scale (NRS), and anxiety levels were measured via the Spielberger State-Trait Anxiety Inventory (STAI). Physiological indices, including systolic and diastolic blood pressure, heart rate, and arterial oxygen saturation, were measured before and after the intervention., Results: Of the 72 patients, 68 completed the study (intervention: n = 35, control: n = 33). Post-intervention, the intervention group showed a significant reduction in systolic (p = 0.017) and diastolic blood pressure (p = 0.028), while the control group experienced no significant changes. Heart rate significantly increased in the control group (p = 0.030), but no significant change was observed in the intervention group (p = 0.977). Anxiety levels significantly decreased in the intervention group (p < 0.001), with a notable between-group difference (p = 0.006). Pain intensity was also significantly lower in the intervention group compared to the control group (p = 0.034)., Conclusion: Foot reflexology is an effective intervention for reducing pain and anxiety in leukemia patients undergoing BMA. Reflexology may be considered a valuable, non-invasive supportive therapy for managing procedural pain and anxiety in oncology settings., 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., (© 2025 The Authors.)

Introduction: Inappropriate use of direct oral anticoagulants (DOACs) is common, affecting up to 30% of atrial fibrillation (AF) population receiving treatment for stroke prevention. This study assessed appropriateness of anticoagulation in anticoagulation-naive AF patients treated with DOACs during a 12-month prospective follow-up., Methods: This prospective cohort study included all anticoagulation-naive AF patients referred for anticoagulation for stroke prevention at a tertiary cardiovascular center. Participants were prospectively followed through phone call interviews by a dedicated nurse at 1, 3, 6, 9, and 12 months after enrollment., Results: Of 403 anticoagulation-naive AF patients, rivaroxaban was prescribed for 325 patients (80.7%) and apixaban for 78 (19.3%). Inappropriate therapy was observed in 23% (76/325) and 46% (36/78) of patients treated with rivaroxaban and apixaban, respectively. Undertreatment was predominant scenario for both drugs, detected in 78.5% (78/112) of patients treated inappropriately, and was more frequently observed with apixaban versus rivaroxaban (44.8% vs 16.3%). During 12 months, inappropriate treatment was corrected in only 13% of all patients. The multivariate regression model identified creatinine clearance ≤ 49 mL/min (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.12 to 4.21), female sex (OR, 1.81; 95% CI, 1.11 to 2.97), and age ≥ 80 years (OR, 1.85; 95% CI, 1.22 to 2.83) as independent covariates associated with inappropriate dosing., Conclusions: Inappropriate therapy with DOACs for stroke prevention in patients with AF is common, and the dosage were corrected in few patients during the 12-month follow-up. Our findings highlight the persistent lack of knowledge regarding appropriate DOAC dosage and need for continuous education., Competing Interests: Declarations. Competing interests: Dr. Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally.  He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multi morbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation program me under grant agreement No 899871., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pain-insomnia-depression syndrome (PIDS) is a complex triad of chronic pain, insomnia, and depression that has profound effects on an individual's quality of life and mental health. The pathobiological context of PIDS involves complex neurobiological and physiological mechanisms, including alterations in neurotransmitter systems and impaired pain processing pathways. The first-line therapeutic approaches for the treatment of chronic pain, depression, and insomnia are a combination of pharmacological and non-pharmacological therapies. In cases where patients do not respond adequately to these treatments, additional interventions such as deep brain stimulation (DBS) may be required. Despite advances in understanding and treatment, there are still gaps in knowledge that need to be addressed. To improve our understanding, future research should focus on conducting longitudinal studies to uncover temporal associations, identify biomarkers and genetic markers associated with PIDS, examine the influence of psychosocial factors on treatment responses, and develop innovative interventions that address the complex nature of PIDS. The aim of this study is to provide a comprehensive overview of these components and to discuss their underlying pathobiological relationships., (© 2024. The Author(s).)

Introduction: The Atrial Fibrillation Better Care (ABC) pathway is such an integrated care approach, recommended in guidelines. The aim of this service evaluation study was to evaluate the impact of implementing the ABC pathway in Iranian population., Methods: In this prospective longitudinal cohort study, consecutive patients with a diagnosis of AF were initially evaluated. Patients at baseline were evaluated in hence of adherence to ABC pathway strategy. After study enrolment, first and second follow-up service evaluations were conducted at 6 and 12 months, respectively., Results: The use of vitamin K antagonists (VKA) decreased from 25.1 % at enrolment to 13.8 % at follow-up; instead, non-VKA oral anticoagulants (NOAC) utilization increased from 40.0 % to 86.1 %, while antiplatelet treatment decreased from 34.9 % to 0 %. Use of antihypertensive drugs, ARBs, diuretics, and statins increased after implementation of the ABC pathway. Implementation of the ABC pathway approach led to a decrease in the occurrence of stroke/TIA (from 6.3 % to 2.2 %, p = 0.002), systemic thromboembolism (from 1.4 % to 0.0 %, p = 0.04), nose bleeds (from 0.8 % to 0.6 %, p = 0.04), skin bruising (from 1.2 % to 0.0 %, p = 0.002), and heart failure (from 7.7 % to 4.7 %, p = 0.04). The proportion of patients in EHRA Class I-II increased from 93.3 % at enrolment to 98.1 % at follow-up., Conclusion: In this first study from a Middle East population, compliance with ABC pathway strategy in the management of AF was associated with optimization of management and general improvements in patient outcomes during follow-up., 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., (© 2024 The Authors.)

Rationale: Fahr syndrome is a rare, degenerative neurological condition characterized by bilateral idiopathic calcification of the periventricular region, especially the basal ganglia. This condition is often misdiagnosed as other neurological or psychiatric disorders due to its rarity and overlapping symptoms., Patient Concerns: A 34-year-old man had been experiencing seizures and cognitive dysfunction for few years, which were further compounded by slurred speech and motor difficulties as acute conditions., Diagnosis: After investigations, severe hypocalcemia, and hypoparathyroidism were detected and his brain computed tomography showed extensive bilateral calcifications in basal ganglia, thalamus, dentate nuclei, and some parts of subcortical white matter, suggestive of Fahr syndrome. Although, the patient was initially misdiagnosed due to a lack of information and the rarity of this disease., Intervention: The patient was treated with intravenous calcium gluconate, vitamin D3, l-ornithine l-aspartate syrup, and levetiracetam, replacing carbamazepine., Outcome: His symptoms, including slurred speech, muscle pain, and stiffness improved, serum calcium normalized, and he was discharged with medications for memory deficit and depression., Lessons: This case underscores the importance of raising awareness among physicians, especially in areas with limited medical resources, about the significance of prompt diagnosis and appropriate symptomatic treatment in enhancing patient prognosis and quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The clinical safety and consequences of upgrade procedures compared with de novo cardiac resynchronisation therapy (CRT) implantation in heart failure remain unclear. The present study aimed to assess clinical and procedural consequences of patients undergoing CRT upgrade as compared to de novo CRT implantations., Methods: In this prospective cohort study, two subgroups were considered as the study population as (1) de novo group that CRT was considered on optimised medical treatment with heart failure of NYHA functional class from II to IV, left ventricular ejection fraction (LVEF) of ≤35%, and QRS width of >130 ms and (2) upgrade group including the patients with previously implantable cardioverter defibrillator (ICD) with the indications for upgrading to CRT. The two groups were compared regarding the changes in clinical outcome and echocardiography parameters., Results: The procedure was successful in 95.9% of patients who underwent CRT upgrade and 100% of those who underwent de novo CRT implantation. It showed a significant improvement in LVEF, severity of mitral regurgitation and NYHA functional classification, without any difference between the two study groups. Overall procedural related complications were reported in 10.8% and 3.8% ( p  = .093) and cardiac death in 5.4% and 2.5% ( p  = .360), respectively, with no overall difference in postoperative outcome between the two groups., Conclusions: Upgrading to CRT is a safe and effective procedure regarding improvement of functional class, left ventricular function status and post-procedural outcome.

Background: Brugada syndrome (BrS) is characterized by ST-segment elevation in the right precordial leads, which is not explained by ischemia, electrolyte disturbances, or obvious structural heart disease., Aim: In present study, we aim to evaluate presentation, long-term outcome, genetic findings, and therapeutic interventions in patients with BrS., Methods: Between September 2001 and June 2022, all consecutive patients with diagnosis of BrS were enrolled in the present study. All patients gave written informed consent for the procedure, and the local ethical committee approved the study., Results: Of the 76 cases, 79% were proband and 21% were detected during screening after diagnosis of BrS in a family member. Thirty-three (43%) patients had a typical spontaneous electrocardiogram (ECG) pattern. Thirty percent of the patients were symptomatic; symptomatic patients were more likely to have spontaneous type 1 Brugada ECG pattern in their ECGs (p = .01), longer PR interval (p = .03), and SCN5A mutation (p = .01) than asymptomatic patients. The mean PR interval was considerably longer in men than women (p = .034). SCN5A mutation was found in 9 out of 50 (18%) studied patients. Fifteen percent received appropriate implantable cardioverter-defibrillator (ICD) therapy and inappropriate ICD interventions were observed in 17%. Presentation with aborted SCD or arrhythmic syncope was the only predictor of adverse outcome in follow-up (odds ratio: 3.1, 95% confidence interval: 0.7-19.6, p = .001)., Conclusions: Symptomatic patients with BrS are more likely to present with spontaneous type 1 Brugada ECG pattern, longer PR interval, and pathogenic mutation in SCN5A gene. Appropriate ICD interventions are more likely in symptomatic patients and those with SCN5A mutation., (© 2024 Wiley Periodicals LLC.)

Background: Cyclophosphamide (CP) has some negative effects on the reproductive system. Stem cells and their metabolites are being utilized to enhance fertility after chemotherapy., Objective: This study aimed to investigate the impact of conditioned medium (CM) derived from bone marrow mesenchymal stromal stem cells (BM-MSCs) on the toxic effects of CP on testicles., Materials and Methods: BM-MSCs were isolated, a CM was collected and 25-fold concentrated. 24 male Wistar rats (8 wk, 200-250 gr) were randomly divided into following groups: control, CP, CP+ Dulbecco's Modified Eagle Medium (DMEM), CP+CM. CP was given at a single dose of 100 mg/kg. 2 wk after the CP administration, CM was injected into the testicular efferent duct. Sperm parameters, testicular histopathology, and the level of testosterone were analyzed 2 months after treatment. The expression of B-cell lymphoma 2 ( Bcl2 ) and Bcl2 -associated X protein ( Bax ) genes were evaluated by real-time polymerase chain reaction., Results: CP had a negative effect on testis histology (p < 0.001) and sperm quality (p < 0.001). It changed the expression of genes associated with apoptosis (p < 0.001). Treatment with CM reduced the expression of Bax (p < 0.001), while significantly increasing the expression of Bcl2 (p = 0.01). It improved sperm count (p = 0.03), viability (p < 0.001), motility (p < 0.001), spermatogonial count (p < 0.001), and epithelial thickness of testicular tubules (p = 0.02)., Conclusion: These findings suggest that CM produced from BM-MSCs may be valuable for therapeutic approaches in reproductive medicine and may lessen the side effects of CP., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Esmailpour et al.)

Conventional chemotherapy has significant limitations for colorectal cancer (CRC) treatment, especially those who have developed metastatic recurrence CRC. A growing number of studies have investigated the potential use of monoclonal antibodies (mAbs) for CRC therapy. mAbs showing clinical benefits for CRC, making the treatment more selective with lower side effects without significant immunogenicity. In addition, recent advancements in antibody engineering strategies and the development of bifunctional or even trifunctional drugs have helped to overcome heterogeneity as the main challenge in cancer treatment. The current review discusses advances in applying mAbs for CRC therapy alone, combined, or with small molecules., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aim: Adiponectin is a member of the adipokine family and contributes to regulating energy homeostasis, reproduction, and various biological functions, such as insulin receptor signaling pathway sensitivity, mitochondrial biogenesis, oxidative metabolism, neurogenesis, and suppression of inflammation. This study aimed to investigate the effects of intracerebroventricular (ICV) injection of adiponectin and its interaction with the neuropeptide Y (NPY) and GABAergic systems on central appetite regulation in neonatal layer-type chickens., Materials & Methods: In this study, 6 experiments were conducted, each of which included 4 experimental groups. In the first experiment, the chickens were injected with saline and adiponectin (20.73, 41.45, and 62.18 nmol). In the second experiment, saline, adiponectin (62.18 nmol), B5063 (NPY1 receptor antagonist, 2.12 nmol), and simultaneous injections of adiponectin and B5063 were performed. Experiments 3 to 6 were done in the same way to experiment 1, but the chickens were injected with SF22 (NPY2 receptor antagonist, 2.66 nmol), SML0891 (NPY5 receptor antagonist, 2.89 nmol), picrotoxin (GABAA receptor antagonist, 0.89 nmol), CGP54626 (GABAB receptor antagonist, 0.047 nmol) instead of B5063. Feed consumption was measured 120 min after the injection., Results: A dose-dependent increase in appetite was observed after the injection of adiponectin (20.73, 41.45, and 62.18 nmol) (P < 0.05). The injection of B5063 + adiponectin attenuated the hyperphagic effect of adiponectin (P < 0.05). In addition, co-injection of picrotoxin and adiponectin significantly decreased adiponectin-induced hyperphagia (P < 0.05). In addition, adiponectin significantly increased the number of steps, jumps, exploratory food, pecks, and standing time, while decreasing sitting time and rest time (P < 0.05)., Conclusion: These results suggest that the hyperphagic effects of adiponectin are probably mediated through NPY1 and GABAA receptors in neonatal layer-type chickens., 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.)

MicroRNAs (miRNAs) have been established as key players in various biological processes regulating differentiation, proliferation, inflammation, and autoimmune disorders. Emerging evidence suggests the critical role of miRNAs in the pathogenesis of multiple sclerosis (MS). Here, we provide a comprehensive overview of miRNAs, which are differentially expressed in MS patients or experimental autoimmune encephalomyelitis (EAE) mice and contribute to MS pathogenesis through regulating diverse pathways, including CD4+ T cells proliferation, differentiation, and activation in three subtypes of CD4+ T cells, including Th1, Th17 and regulatory T cells (Tregs). Moreover, the regulation of oligodendrocyte precursor cells (OPC) differentiation as a crucial player in MS pathogenesis is also described. Our literature research showed that miR-223 could affect different pathways involved in MS pathogenesis, such as promoting Th1 differentiation, activating the M2 phenotype of myeloid cells, and clearing myelin debris. MiR-223 was also identified as a potential biomarker, distinguishing relapsing-remitting multiple sclerosis (RRMS) from progressive multiple sclerosis (PMS), and thus, it may serve as an attractive target for further investigations. Our overview provides novel potential therapeutic targets for the treatment and new insights into miRNAs' role in MS pathogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A U-shaped contraction pattern was shown to be associated with a better Cardiac resynchronization therapy (CRT) response. The main goal of this study is to automatically recognize left ventricular contractile patterns using machine learning algorithms trained on conventional quantitative features (ConQuaFea) and radiomic features extracted from Gated single-photon emission computed tomography myocardial perfusion imaging (GSPECT MPI). Among 98 patients with standard resting GSPECT MPI included in this study, 29 received CRT therapy and 69 did not (also had CRT inclusion criteria but did not receive treatment yet at the time of data collection, or refused treatment). A total of 69 non-CRT patients were employed for training, and the 29 were employed for testing. The models were built utilizing features from three distinct feature sets (ConQuaFea, radiomics, and ConQuaFea + radiomics (combined)), which were chosen using Recursive feature elimination (RFE) feature selection (FS), and then trained using seven different machine learning (ML) classifiers. In addition, CRT outcome prediction was assessed by different treatment inclusion criteria as the study's final phase. The MLP classifier had the highest performance among ConQuaFea models (AUC, SEN, SPE = 0.80, 0.85, 0.76). RF achieved the best performance in terms of AUC, SEN, and SPE with values of 0.65, 0.62, and 0.68, respectively, among radiomic models. GB and RF approaches achieved the best AUC, SEN, and SPE values of 0.78, 0.92, and 0.63 and 0.74, 0.93, and 0.56, respectively, among the combined models. A promising outcome was obtained when using radiomic and ConQuaFea from GSPECT MPI to detect left ventricular contractile patterns by machine learning., (© 2022. The Author(s).)

Background: The subcutaneous implantable-defibrillator (S-ICD) is a relatively new alternative to the transvenous ICD system to minimize intravascular lead-related complications. This paper presents outcome of SICD implantation in patients enrolled in Iran S-ICD registry., Methods: Between October 2015 and June 2022, this prospective multicenter national registry included 223 patients with a standard indication for an ICD, who neither required bradycardia pacing nor needed cardiac resynchronization to evaluate the early post-implant complications and long-term follow-up results of the S-ICD system., Results: The mean age of the patients was 45 ± 17 years. The majority (79.4%) were male. Ischemic cardiomyopathy (39.5%) was the most common underlying disorder among patients selected for S-ICD implant. Most study patients (68.6%) had ICD for primary prevention of sudden cardiac death. Seven patients (3.1%) were found to have suboptimal lead positions. Six patients (2.7%) developed a pocket hematoma; all were managed medically. During a mean follow-up of 2 years, the appropriate therapy was recorded in 13% of the patients and inappropriate ICD intervention mainly due to supraventricular tachycardia in 8.9%. Pocket infection was observed in four patients (1.8%) and five patients (2.2%) died mainly due to heart failure., Conclusion: S-ICDs were effective at detecting and treating both induced and spontaneous ventricular arrhythmias. Major clinical complications were rare., (© 2023 Wiley Periodicals LLC.)

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre-eclampsia  are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid-derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications., (© 2022 International Federation for Cell Biology.)

SOHLH1 and NOBOX are oocyte-expressed transcription factors with critical roles in ovary development and fertility. In mice, Sohlh1 and Nobox are essential for fertility through their regulation of the oocyte transcriptional network and cross-talk to somatic cells. Sumoylation is a posttranslational modification that regulates transcription factor function, and we previously showed that mouse oocytes deficient for sumoylation had an altered transcriptional landscape that included significant changes in NOBOX target genes. Here, we show that mouse SOHLH1 is modified by SUMO2/3 at lysine 345 and mutation of this residue alters SOHLH1 nuclear to cytoplasmic localization. In NOBOX, we identify a non-consensus SUMO site, K97, that eliminates NOBOX mono-SUMO2/3 conjugation, while a point mutation at K125 had no effect on NOBOX sumoylation. However, NOBOX K97R/K125R double mutants showed loss of mono-SUMO2/3 and altered higher molecular weight modifications, suggesting cooperation between these lysine's. NOBOX K97R and NOBOX K97R/K125R differentially regulated NOBOX promoter targets, with increased activity on the Gdf9 promoter, but no effect on the Pou5f1 promoter. These data implicate sumoylation as a novel regulatory mechanism for SOHLH1 and NOBOX, which may prove useful in refining their roles during oogenesis as well as their function during reprogramming to generate de novo germ cells., (© 2023 Federation of American Societies for Experimental Biology.)

Introduction: Epicardial pacemakers are known as an alternative for endocardial pacemakers in some cases such as heart block, and complex congenital heart diseases. Considering recent advances and improvement of epicardial lead subtypes, it is essential to investigate the long-term function of them. In this study, we aimed to assess the sensing and pacing characteristics, and survival of bipolar steroid-eluting and unipolar nonsteroid-eluting epicardial pacemakers., Methods: We conducted an entirely concentrated search on the documents of all patients who had undergone epicardial lead implantation in the Shaheed Rajaie Cardiovascular, Medical & Research Center during 2015-2018. Implant, and follow-up data were extracted. Kaplan-Meier analysis and Weibull regression hazards model were applied for the survival analysis., Results: Eighty-nine leads were implanted for 77 patients. Of the total leads, 52.81%, 53.93%, and 47.19% were implanted in children (under 18-year-old), females, and patients with congenital heart diseases, respectively. Bipolar steroid-eluting leads comprised 33.71% of 89 leads. The pacing threshold of unipolar nonsteroid-eluting leads that were implanted on the left ventricle and right atrium increased significantly during the follow-up to greater records than bipolar steroid-eluting leads. Survival analysis also revealed that bipolar steroid-eluting leads are significantly better in 48-month survival (Weibull hazard ratio [HR]: 0.13 (95% confidence interval [CI]: 0.02-0.99), p = .049). Age, ventricular location of the lead, and acute pacing characteristics were not associated with survival., Conclusions: Bipolar steroid-eluting epicardial leads have an acceptable survival compared with unipolar nonsteroid-eluting, without a significant difference regarding patients age. Therefore, they could be an excellent alternative for endocardial ones., (© 2022 Wiley Periodicals LLC.)

Background and Aims: Health care workers (HCWs) are thought to be high-risk population for acquiring coronavirus disease (COVID-19). The COVID-19 emergence has had a profound effect on healthcare system. We sought to investigate the COVID-19 among HCWs and their effects on the healthcare system., Methods: A cross sectional observational study was conducted at Timergara teaching hospital. The study included HCWs with positive real time polymerase chain reaction (Q-PCR) for severe acute respiratory syndrome coronavirus (SARS-CoV-2). The study duration was from April to September, 2020. The demographic profile of each recruited subject was collected through structured interview. The patient's admissions to hospital were collected for the 5 months before (October 2019-February 2020) and 5 months after lockdown (March-July 2020)., Results: A total of 72 out of 689 (10%) HCWs were tested positive for SARS-CoV-2, of whom 83% were front-liners. The majority were male (72%), with comorbidities (14%) and no mortality. The structured interview of all participants showed that the healthcare setting was the major possible source of infection (97%). The patient admissions into the hospital were reduced by 42% during lockdown than prelockdown period. The patients admission was significantly decreased in the medical ward during lockdown (60% decrease; p  < 0.01) with slightly similar trends in other departments., Conclusion: In conclusion, we found increased risk of COVID-19 for front-line HCWs. Lack of mortality was the favorable outcome. Lack of replacing the infected HCWs possibly explained the marked decrease in hospital admissions, and potential inadequate healthcare delivery during the lockdown. Understanding SARS-CoV-2 among HCWs and their impact on health-care system will be crucial for countries under COVID-19 crises or in case of future pandemic to deliver proper health services., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Astrocytes display an active, dual, and controversial role in multiple sclerosis (MS), a chronic inflammatory demyelination disorder. However, mesenchymal stem cells (MSCs) can affect myelination in demyelinating disorders. This study aimed to investigate the effect of single and combination therapies of astrocyte ablation and MSC transplantation on remyelination in the cuprizone (CPZ) model of MS. C57BL/6 mice were fed 0.2% CPZ diet for 12 weeks. Astrocytes were ablated twice by L-a-aminoadipate (L-AAA) at the beginning of weeks 13 and 14 whereas MSCs were injected in the corpus callosum at the beginning of week 13. Motor coordination and balance were assessed through rotarod test whereas myelin content was evaluated by Luxol-fast blue (LFB) staining and transmission electron microscopy (TEM). Glial cells were assessed by immunofluorescence staining while mRNA expression was evaluated by quantitative real-time PCR. Combination treatment of ablation of astrocytes and MSC transplantation (CPZ + MSC + L-AAA) significantly decreased motor coordination deficits better than single treatments (CPZ + MSCs or CPZ + L-AAA), in comparison to CPZ mice. In addition, L-AAA and MSCs treatment significantly enhanced remyelination compared to CPZ group. Moreover, combination therapy caused a significant decrease in the number of GFAP + and Iba-1 + cells, whereas oligodendrocytes were significantly increased in comparison to CPZ mice. Finally, MSC administration resulted in a significant upregulation of BDNF and NGF mRNA expression levels. Our data indicate that transient ablation of astrocytes along with MSCs treatment improve remyelination through enhancing oligodendrocytes and attenuating gliosis in a chronic demyelinating mouse model of MS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: There is no conflict of interest between all the authors.

Background: Atrial fibrillation (AF) with fast ventricular response over an overt accessory pathway (AP) (preexcited AF) with a short anterograde refractory period is a potentially malignant arrhythmia. This study aimed to evaluate the safety and efficacy of amiodarone for preexcited AF management., Materials and Methods: This study enrolled 103 patients with evidence of AP in electrocardiography. Patients with preexcited AF were included in the study. Intravenous amiodarone (300 mg) was infused for 30 min for all patients in the AF rhythm. Electrophysiological parameters were evaluated before amiodarone injection and 2 h after pharmacological or electrical cardioversion., Results: Antegrade and retrograde refractory periods of the atrioventricular node (AVN) and AP, as well as antegrade and retrograde Wenckebach points of AVN, were increased significantly after amiodarone infusion. Furthermore, the mean of the shortest preexcited RR interval was increased during the monitoring period. Comparing the preexcited index at the beginning of the study and before cardioversion (2 h later) revealed that the QRS complexes changed to a wider pattern as the preexcitation index changed from 80.61 to 92.26 ( P < 0.001). Nineteen (18.4%) patients converted to the sinus rhythm with amiodarone infusion. No ventricular arrhythmia was detected during monitoring., Conclusion: Amiodarone could be considered a safe drug in patients with preexcited AF for rate control despite its relatively low efficacy in conversion to the sinus rhythm., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Research in Medical Sciences.)

Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T-cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T-cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoint factors, including PD-1, LAG-3, CTLA-4, and TIM-3 in normal pregnant women and PE patients. Decidual tissue was collected from 50 participants (25 PE and 25 control). For evaluating the genes expression, real-time PCR was employed. The western blot was used to assess the proteins level. The results of real-time PCR indicated significantly decreased expression level of these immune checkpoints in PE patients. In parallel to gene expression results, the protein level of PD-1, LAG-3, CTLA-4, and TIM-3 in the PE group was also reduced. We revealed that the profile of proteins and genes expression of immune checkpoints in the decidua of PE mothers are different from normal pregnancy and these results indicate aberrant expression of immune checkpoints such as PD-1, LAG-3, CTLA-4, and TIM-3 may cause maladaptation immune response which results in PE manifestation., 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 © 2022 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Analysis of miRNAs has a strong potential for the identification of novel prognostic or predictive biomarkers in the serum of AD patients. In this study, we investigated the serum levels of miR-106b as a diagnostic biomarker for AD and evaluate its predictive value for therapeutic response to the drug rivastigmine. Patients were divided into either responding ( n  = 33) or non-responding ( n  = 23) groups according to rivastigmine treatment and to Mini-Mental State Exam score. The serum concentrations of miR-106b were measured with real-time PCR. Here, we found that miR-106b was significantly down-regulated in the serum samples of AD patients compared with those of controls ( p  < .001). ROC results showed a specificity of 62% and a sensitivity of 94%. The serum values of miR-106b tended to be positively associated with the therapeutic response but were not significant ( p  = .15). Taken together, detection of serum miR-106b might be a promising serum biomarker for early diagnosis of AD.

Background: Cryostorage of spermatogonial stem cells (SSCs) is an appropriate procedure for long-term storage of SSCs for fertility preservation. However, it causes damage to cellular structures through overproduction of ROS and oxidative stress. In this study, we examined the protective effect of melatonin as a potent antioxidant in the basic freezing medium to establish an optimal cryopreservation method for SSCs., Methods: SSCs were obtained from the testes of neonatal male mice aged 3-6 days. Then, 100 μM melatonin was added to the basic freezing medium containing DMSO for cryopreservation of SSCs. Viability, apoptosis-related markers (BAX and BCL2), and intracellular ROS generation level were measured in frozen-thawed SSCs before transplantation using the MTT assay, immunocytochemistry, and flow cytometry, respectively. In addition, Western blotting and immunofluorescence were used to evaluate the expression of proliferation (PLZF and GFRα1) and differentiation (Stra8 and SCP3) proteins in frozen-thawed SSCs after transplantation into recipient testes., Results: The data showed that adding melatonin to the cryopreservation medium markedly increased the viability and reduced intracellular ROS generation and apoptosis (by decreasing BAX and increasing BCL2) in the frozen-thawed SSCs (p < 0.05). The expression levels of proliferation (PLZF and GFRα1) and differentiation (Stra8 and SCP3) proteins and resumption of spermatogenesis from frozen-thawed SSCs followed the same pattern after transplantation., Conclusions: The results of this study revealed that adding melatonin as an antioxidant to the cryopreservation medium containing DMSO could be a promising strategy for cryopreservation of SSCs to maintain fertility in prepubertal male children who suffer from cancer., (© 2022. The Author(s).)

The catheter ablation of idiopathic ventricular arrhythmias is accepted as a first-line treatment as it successfully eliminates about 90.0% of such arrhythmias. One of the most challenging ventricular arrhythmias originates from the left ventricular summit (LVS), a triangular epicardial space with the left main bifurcation as its apex. This area accounts for about 14.0% of LV arrhythmias. The complex anatomy of this region, accompanied by proximity to the major epicardial coronary arteries and the presence of a thick fat pad in this region, renders it a challenging area for catheter ablation. This article presents a review of the anatomy of the LVS and relevant regions and discusses novel mapping and ablation techniques for eliminating LVS ventricular arrhythmias. Additionally, we elaborate on the electrocardiographic (ECG) manifestations of arrhythmias from the LVS and their successful ablation via the direct approach and the adjacent structures., (Copyright © 2022 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Objective: Self-medication with antibiotics (SMA) is a common cause of antibiotic resistance, a major public health problem. This research aimed to identify the prevalence of SMA and explore reasons for practicing SMA among people living in Kabul, Afghanistan., Methods: A community-based cross-sectional study was conducted from May to November 2017 in 12 community pharmacies operating across Kabul, Afghanistan. Multivariable logistic regression was conducted to identify the factors associated with the use of SMA., Results: Out of 385 participants, 282 (73.2%) practiced SMA during the last year. Overall, 241 (62.6%) were 'very concerned' about the use of SMA, and 156 (40.5%) highlighted it is bad to practice SMA. The top three antibiotics used for self-medication were penicillin (ATC class: J01C), metronidazole (ATC: P01AB01), and ceftriaxone (ATC: J01DD04). Economic problems, lack of time to visit doctors, and ease of use were cited as the main reasons for practicing SMA. Furthermore, female participants were less likely to practice SMA compared to male counterparts., Conclusion: While efforts should be directed to enforce strict drug regulations system and awareness programs, priority should be given to provide accessible, affordable, and quality health care services to increase citizen's compliance to appropriate drug prescriptions.

Different molecular signaling pathways have been involved in the incidence and progression of CRC. We aimed to examine the correlation between eight candidate genes, including TFGβ, SMAD2, SMAD4, RhoA, EGFR, MAP2K1, MTA1, and LEF1 in the progression of colorectal cancer (CRC) and their association with clinicopathological variables and CRC patients prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) analysis 2 -ΔΔct , were performed to assess the expression of eight genes in 64 and 122 patients with CRC, respectively and 20 normal samples were added for verification. We showed a positive correlation between SMAD2 and MAP2K1 (r = 0.337, P < 0.001), MAP2K1 and LEF1 (r = 0.187, P = 0.03), SMAD4 and RhoA (r = 0.214, P = 0.01) and as well, a negative correlation between SMAD2 and TGFβ (r =  - 0.197, P = 0.02), and RhoA and LEF1 (r =  - 0.180, P = 0.04) in tumor tissues. A decrease in RhoA mRNA expression was associated with the advanced TNM stage (P = 0.01), while the EGFR and SMAD2 mRNA expression upregulated in advanced stages (P = 0.03, P = 0.03), respectively. Also, an increase in EGFR and SMAD4 protein expression was significantly associated with the advanced TNM stage (P = 0.000) (P = .002), respectively. Perceiving the connections between canonical and non-canonical Transforming growth factor (TGF-β) signaling pathway along with the epidermal growth factor receptor (EGFR) and WNT cascades may trigger the development of novel approaches for CRC prediction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Haemophilia is a well-known bleeding disorder that affects people worldwide. The main therapeutic strategy is regular infusion of exogenous factor VIII to ensure an optimal haemostatic standard. Morbidity and mortality of individuals with haemophilia has decreased in developing countries due to improvement in early detection, advanced treatments, and comprehensive population outreach efforts. However, individuals with bleeding disorders in developing countries like Afghanistan do not have access to such therapeutic facilities., Aims: The goals of this study were to determine the causes of death and findings related to death among in individuals with bleeding disorders in Afghanistan., Methods: This study conducted as a retrospective cross-sectional study of 387 individuals with bleeding disorders (mainly haemophilia) in Afghanistan., Results: All registered individuals with bleeding disorders in Afghanistan were interviewed by telephone. Among the 387 individuals with bleeding disorders, there were 136 deaths. Most deaths occurred in individuals aged 1-15 years (66.2%). Intracranial haemorrhage was the leading cause of death in individuals with haemophilia A and B., Conclusion: These findings revealed that supply of coagulation factor concentrates, facilities for haemostasis diagnosis, and trained haematologists is inadequate in Afghanistan., (© 2021 John Wiley & Sons Ltd.)

Objectives: The present study aimed to investigate the potential delays in healthcare seeking and diagnosis of women with cervical cancer (CC) in Afghanistan. Methods: Clinical records of three hospitals in Kabul were searched for CC cases, and the women identified were interviewed by a trained physician using a semi-structured questionnaire. The main outcomes were the prevalence of potential delays over 90 days (1) from symptoms onset to healthcare seeking (patient delay), and (2) from first healthcare visit to CC diagnosis (healthcare delay). Information was also collected on: type and stage of CC, diagnostic test utilized, familiarity for CC, signs and symptoms, treatment type, and potential reasons for delaying healthcare seeking. Results: 31 women with CC were identified, however only 11 continued their treatment in the study hospitals or were reachable by telephone, and accepted the interview. The mean age was 51 ± 14 years, and only 18.2% had a previous history of seeking medical care. Patient delay was seen in 90.9% of the women (95% CI: 58.7-99.8), with a median of 304 ± 183 days. Instead, healthcare delay was found in 45.4% (95% CI: 16.7-76.6), with a median of 61 ± 152 days. The main reasons for patient delays were unawareness of the seriousness of the symptoms (70.0%) and unwillingness to consult a healthcare professional (30.0%). None of the women ever underwent cervical screening or heard of the HPV vaccination. Conclusions: Given the global effort to provide quality health care to all CC patients, Afghanistan needs interventions to reduce the delays in the diagnosis of this cancer, for instance by improving all women's awareness of gynecological signs and symptoms., 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 © 2021 Acuti Martellucci, Delsoz, Qaderi, Madadi, Bhandari, Ozaki and Mousavi.)

Background: Atrioventricular node (AVN) is an interatrial septum structure located at the apex of triangle of Koch that modulates the transmission of impulses from atria to the ventricles. Vagally mediated AVN block with high frequency stimulation (HFS) was investigated in a few animal and human studies, but prolonged ventricular asystole that was induced by a low frequency proximal coronary sinus (CS) overdrive pacing has rarely been reported., Case Report: A 40-year-old man was admitted in our hospital for evaluation of syncope and palpitation. He presented with prolonged ventricular asystole by proximal CS pacing during electrophysiological study (EPS)., Conclusion: There is no comprehensive clinical study to investigate the association of vasovagal syncope with vagally mediated atrioventricular block (AVB) which is induced by posteroseptal area stimulation. Radiofrequency catheter ablation of ganglionated plexi (GP) located close to sinus node and AVN was reported to eliminate the vagal efferent output during vasovagal syncope as a new treatment strategy., (© 2021 Isfahan Cardiovascular Research Center & Isfahan University of Medical Sciences.)