Search

The effectiveness of immunotherapy for most cancer patients remains low, with approximately 10-30% of those treated surviving. Thus, much effort is being put into finding new ways to improve immune checkpoint therapy. Our review concludes that inhibition of proprotein convertase subtilisin/Kexin type 9 (PCSK9), which plays a critical role in regulating cholesterol metabolism, can cause movement of T cells toward tumors, with increased sensitivity to immune checkpoint therapies. We searched PubMed, NCBI, Scopus, and Google Scholar for the published articles without limitations on publication dates. We used the following terms: "PCSK9", "Cancer", "Immune Checkpoint", and "Cancer Prognosis" in the title and/or abstract. Our search initially revealed 600 records on the subject and stored them in the used databases under EndNote X8 management software. A total of 161 articles were selected and through a careful review, 76 were included in our research. We concluded that PCSK9 reduces the number of LDL receptors (LDL-R) on the cell surface, which is linked to its ability to regulate cholesterol levels in the body. Also, we discuss how suppressing PCSK9 leads to the MHC-1 accumulation on the surface of cancer cells, which results in T lymphocyte invasion. Finally, we believe that inhibiting PCSK9 may be an effective strategy for improving cancer immunotherapy., Competing Interests: The authors declared no conflict of interest., (© 2024.)

Introduction: Cortical lesions can cause major sensory and motor impairments, representing a significant challenge in neuroscience and clinical medicine. Limbal mesenchymal stem cells (LMSCs), renowned for their remarkable ability to proliferate and distinct characteristics within the corneal epithelium, offer a promising opportunity for regenerative treatments. This study aimed to assess whether the transplantation of LMSCs could improve tactile ability in rats with lesions of the barrel cortex., Methods: In this experimental study, we divided 21 rats into three groups: a control group, a lesion group with cortical cold lesion induction but no stem cell treatment, and a group receiving LMSC transplantation following cold lesion induction. We conducted 3-week sensory assessments using a texture discrimination test and an open-field test. We also performed Nissl staining to assess changes on the cellular level., Results: Rats in the LMSC transplantation group demonstrated significant improvements in their ability to discrimination textures during the second and third weeks compared to those in the lesion group. The open-field test results showed an increased exploratory behavior of rats in the LMSC transplantation group by the third week compared to the lesion group. Additionally, Nissl staining revealed cellular alterations in the damaged cortex, with a significant distinction observed between rats in the LMSCs and lesion group., Conclusion: The findings suggest that LMSC transplantation enhances sensory recovery in rats with cortical lesions, particularly their ability to discriminate textures. LMSC transplantation benefits brain tissue reparation after a cold lesion on the somatosensory cortex., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120 mg MgO, 120 mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.

In general, the majority of fiber-reinforced polymer composites (FRPs) used in structural applications comprise carbon, glass, and aramid fibers reinforced with epoxy resin, with the occasional utilization of polyester and vinyl ester resins. This study aims to assess the feasibility of utilizing recyclable and sustainable materials to create a resilient composite suitable for structural applications, particularly in scenarios involving low-velocity and high-velocity impact (LVI, HVI) loading. The paper presents a comparative analysis of the performance of E-glass, aramid, and eco-friendly basalt-reinforcing fabrics as reinforcement fibers in both thermosetting (epoxy) and recyclable thermoplastic (Elium © ) resins. Given the limited research on Elium composites, especially those incorporating basalt-reinforcing fiber, there is an urgent need to expand the databases of fundamental mechanical properties for these diverse composites. This necessity is exacerbated by the scarcity of the literature regarding their performance under low- and high-velocity impact loadings. The results of this study will demonstrate the potential of basalt-reinforced Elium composite as an effective recyclable and environmentally friendly structural material system for both static and dynamic loading conditions.

Background: The percentage of brain tumor incidence exceeds 50% in the geriatric population admitted at Khoula Hospital (a tertiary care hospital in Oman) as compared to the younger population, furthermore, geriatric patients impose a higher cost of healthcare in general. Therefore, geriatric tumor care is causing a significant burden on the healthcare service in Oman. For this reason, we have developed this study to identify the cost of care for this group., Methods: Medical data with their costs were collected retrospectively for 108 patients diagnosed with a brain tumor above the age of 65 years and admitted at Khoula Hospital between 2016 and 2019., Results: The two most common diagnoses in terms of incidence were Meningiomas (31.73%) and Glioblastomas (16.34%). Lymphoma peaked with regards to the cost, with an average cost of 8993.83 USD per diagnosis, followed by glioblastoma and then metastatic lesions (with 5039.18 and 4915.76 USD respectively). Of these surgeries, 82.61% were elective, most of which had a cost above or equal to the average. Emergency surgeries showed equal numbers above and below the average cost of surgeries (P< 0.05). The total costs of imaging were 73759.4 USD, with CT (35.8%) + MRI (32.9%) forming 68.7% of the total imaging costs. While laboratory investigation costs totaled 64110.93 USD., Conclusion: The cost of tumor care in Oman is variable based on multiple factors. The reported results represent useful information forming the basis for further analysis such as cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis.

Single-cell RNA sequencing is a high-throughput novel method that provides transcriptional profiling of individual cells within biological samples. This method typically uses microfluidics systems to uncover the complex intercellular communication networks and biological pathways buried within highly heterogeneous cell populations in tissues. One important application of this technology sits in the fields of organ and stem cell transplantation, where complications such as graft rejection and other post-transplantation life-threatening issues may occur. In this review, we first focus on research in which single-cell RNA sequencing is used to study the transcriptional profile of transplanted tissues. This technology enables the analysis of the donor and recipient cells and identifies cell types and states associated with transplant complications and pathologies. We also review the use of single-cell RNA sequencing in stem cell implantation. This method enables studying the heterogeneity of normal and pathological stem cells and the heterogeneity in cell populations. With their remarkably rapid pace, the single-cell RNA sequencing methodologies will potentially result in breakthroughs in clinical transplantation in the coming years.

The integration of additive manufacturing technologies with the pyrolysis of polymeric precursors enables the design-controlled fabrication of architected 3D pyrolytic carbon (PyC) structures with complex architectural details. Despite great promise, their use in cellular interaction remains unexplored. This study pioneers the utilization of microarchitected 3D PyC structures as biocompatible scaffolds for the colonization of muscle cells in a 3D environment. PyC scaffolds are fabricated using micro-stereolithography, followed by pyrolysis. Furthermore, an innovative design strategy using revolute joints is employed to obtain novel, compliant structures of architected PyC. The pyrolysis process results in a pyrolysis temperature- and design-geometry-dependent shrinkage of up to 73%, enabling the geometrical features of microarchitected compatible with skeletal muscle cells. The stiffness of architected PyC varies with the pyrolysis temperature, with the highest value of 29.57 ± 0.78 GPa for 900 °C. The PyC scaffolds exhibit excellent biocompatibility and yield 3D cell colonization while culturing skeletal muscle C2C12 cells. They further induce good actin fiber alignment along the compliant PyC construction. However, no conclusive myogenic differentiation is observed here. Nevertheless, these results are highly promising for architected PyC scaffolds as multifunctional tissue implants and encourage more investigations in employing compliant architected PyC structures for high-performance tissue engineering applications., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Currently, fiber-reinforced polymer composites (FRPs) used for demanding structural applications predominantly utilize carbon, glass, and aramid fibers embedded in epoxy resin, albeit occasionally polyester and vinyl ester resins are also used. This study investigates the feasibility of employing recyclable and sustainable materials to formulate a composite suitable for load-bearing structural applications, particularly in scenarios involving low-velocity and high-velocity impacts (LVIs and HVIs, respectively). The paper presents a comparative analysis of the performance of basalt-Elium, a fully recyclable, sustainable, and environmentally friendly composite, with an epoxy-based counterpart. Moreover, an accurate and reliable numerical model has been developed and introduced through which the response of these composites can be examined efficiently and accurately under various loading states. The results of this investigation demonstrate the viability of the basalt-elium composite as a fully recyclable and sustainable material for crafting efficient and lightweight composites. Additionally, the accurately developed finite element model presented here can be used to assess the influence of several parameters on the composite, thereby optimizing it for a given situation.

Background: The objective of this study was to examine analgesia when using perineural dexamethasone compound in an interscalene brachial plexus block following shoulder surgery., Methods: This study was designed as a randomized, double-blind clinical trial. Patients meeting the specified criteria were randomly divided into two groups: The experimental group and the control group, each comprising 30 individuals. Age and gender were matched between the groups. The control group received lidocaine along with 2 cc of 0.5% bupivacaine (20 milligrams) and 2 cc of normal saline; however, the experimental group received lidocaine, along with 2 cc of 0.5% bupivacaine and 2 cc of dexamethasone. Pain levels were assessed using the Visual Analog Scale (VAS), and covariance analysis was applied for data analysis., Results: The results demonstrated that pain intensity was notably lower in the experimental (dexamethasone) group than in the control group at both the 12-hour group (P < 0.001) and 24-hour (P < 0.001) postoperative marks. Dexamethasone significantly reduced pain among the patients., Conclusions: In conclusion, administering dexamethasone to potential candidates for shoulder surgery could lead to prolonged analgesia for up to 24 hours after the surgery. Consequently, this medication can serve as an efficacious analgesic option for pain management in these patients., Competing Interests: The authors declare no significant interest with commercial supporters., (Copyright © 2024, Ghasemi et al.)

Background: During natural catastrophes, hospital staff members' readiness for crisis management-particularly concerning patient evacuation and improving their safety-becomes paramount. This study aimed to identify the components contributing to hospital staff members' preparedness to evacuate patients in an emergency., Method: A systematic review was conducted by searching databases such as Scopus, Web of Science, PubMed, ProQuest, and grey literature through May 2023. Studies that offered unique qualitative or quantitative data regarding hospital personnel readiness to evacuate patients in an emergency were included. Thematic analysis and descriptive statistics were used to examine the extracted data points., Results: In total, there were 274 scientific articles. The total number of unique studies decreased to 181 after removing duplicate articles. 28 papers that were deemed appropriate for additional study were found based on the titles and abstracts of these articles. Eighteen papers that met the inclusion criteria were selected for the systematic review after their entire texts were finally assessed. Hospital staff preparedness for patient evacuation was divided into four primary topics and nineteen sub-themes. The four primary themes that emerged were management, communication, individual issues, and training on the evacuation process., Conclusion: The implementation of proper disaster evacuation training programs can be achieved by elevating the perceived sensitivity and protective motive of personnel and considering the personnel's stages of change. Training hospital staff to properly evacuate patients during disasters is also significantly impacted by other factors, such as effective administration, leadership and prompt and efficient communication., (© 2024. The Author(s).)

Background and Aim: Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury., Materials and Methods: Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05)., Results: Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties., Conclusion: Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility., (© 2024 Wiley Periodicals LLC.)

Purpose: Toxoplasmosis is a disease caused by infection with a type of coccidial protozoan parasite called Toxoplasma gondii. The relationship between toxoplasmosis and cognitive disorders in neurodegenerative diseases has been proven. There is also evidence that children born to Toxoplasma-infected mothers are more likely to develop autism., Methods: In the present study, Toxoplasma-infected pregnant BALB/c mice were given valproic acid to induce autism in their male offspring, and their social behaviors, learning, and memory were examined. Chronic toxoplasmosis was established in BALB/c mice by intraperitoneal injection of cyst form of T. gondii. To induce autism, 600 mg/kg of valproic acid was injected intraperitoneally into mice on the 12.5th day of pregnancy. The behavioral experiments, such as social interaction, novel object recognition, and passive avoidance tasks, were performed on male offspring at 50 days., Results: Toxoplasma and valproic acid during the embryonic period caused social communication deficits and disrupted recognition memory and avoidance memory in offspring. Our findings showed that administering valproic acid to Toxoplasma-infected mothers exacerbates cognitive disorders in their offspring., (© 2023 International Society for Developmental Neuroscience.)

Background: Autism spectrum disorder (ASD) represents an inheritable neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Numerous studies have underscored the significant roles played by genetic and environmental factors in the etiology of ASD, and these factors are known to perpetuate behavioral impairments across generations., Objectives: The primary objective of this study was to assess the behavioral and cognitive attributes in the second filial (F2) generation of male and female rats, with a particular focus on those whose parents had been exposed to valproic acid (VPA) during embryonic development., Methods: In this study, a cohort of 32 male and 32 female rats from the second filial (F2) generation, referred to as Mother.ASD, Father.ASD, or Both.ASD, was examined. These designations indicate whether the mother, father, or both parents had experienced embryonic exposure to valproic acid (600 mg/kg, i.p.). During adolescence, the F2 pups underwent behavioral and cognitive assessments, including open field testing, marble burying, social interaction evaluations, and Morris water maze tasks., Results: Our data revealed that while both the Mother.ASD and Father.ASD groups, regardless of sex, exhibited elevated anxiety-like behavior in the open field test. Only the Mother.ASD group displayed repetitive behaviors and deficits in social memory. Additionally, spatial memory impairments were observed in both sexes. These findings highlight the transmission of autistic-like behaviors in the offspring of Mother.ASD rats from both sexes. Nevertheless, future research endeavors should be more targeted in identifying the specific genes responsible for this transmission., Conclusion: In summary, our findings underscore the transmission of autistic-like behaviors, including anxiety-like behavior, repetitive actions, impairments in social interactions, and deficits in memory, to the offspring of the Mother.ASD group, irrespective of their sex., (© 2024 Wiley Periodicals LLC.)

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive behaviors and interests. In previous studies, music has been identified as an intervention therapy for children with ASD., Objectives: The present study evaluated the effects of music on cognitive behavioral impairments in both sexes of adult rats exposed prenatally to Valproic acid., Methods: For induction of autism, pregnant female rats were pretreated with either saline or VPA (600 mg/kg.i.p.) at gestational day (GD) 12.5. Male and female offspring were divided into Saline.Non-Music, VPA.Non-Music, Saline.Music, and VPA.Music groups. The adult rats in the music groups were exposed to Mozart's piano sonata K.448 for 30 days (4 h/day), from postnatal day (PND) 60 to 90. Social interaction and Morris water maze (MWM) tasks were tested at PND 90., Results: Our results revealed that prenatal exposure to VPA decreased sociability and social memory performance in both sexes of adult rats. Moreover, prenatal exposure to VPA created learning and memory impairments in both sexes of adult rats in the MWM task. Music intervention improved sociability in both sexes of VPA-exposed rats and social memory in both sexes of VPA-exposed rats, especially in females. Furthermore, our results revealed that music ameliorated learning impairments in VPA-exposed female rats in the MWM task. In addition, music improved spatial memory impairments in VPA-exposed rats of both sexes, especially in females, which needs more investigation in molecular and histological fields in future studies., Conclusion: Music intervention improved sociability and social memory in adult VPA-exposed rats, especially in female animals. Furthermore, music improved memory impairments in VPA-exposed rats of both sexes. It seems that music had a better influence on female rats. However, future studies need more investigations in molecular and histological fields., (© 2024 Wiley Periodicals LLC.)

Introduction: Both sleep deprivation (SD) and inflammation can negatively affect cognitive function. This study aimed to investigate how SD impacts the brain's inflammatory response to lipopolysaccharide (LPS) and its subsequent effects on cognitive functions., Methods: To this end, male rats were tested through a Morris water maze (MWM) to assess their spatial learning and memory. Also, in vivo field potential recordings (to evaluate synaptic plasticity) were done in the Saline, SD, LPS1 (1 mg/kg/7 days), and LPS1+SD groups. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA)., Results: Based on the results, the LPS1+SD group showed increased total distance and escape latency compared to the other groups in the MWM test. Besides, the LPS1+SD group exhibited a significant decrease in long-term potentiation (LTP) induction and maintenance in the CA1 area of the brain. Finally, the inflammatory cytokine interleukin-1β (IL-1β) levels were significantly higher in the LPS1+SD group than in the Saline group., Conclusion: These findings suggest that the combined effects of SD and brain inflammatory response can have more harmful effects on cognitive function, LTP, and inflammatory factors than either SD or LPS1 alone., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The new Knee Society Knee Scoring System (KSS) has been widely used to assess the symptoms, satisfaction, expectations, and physical activities of patients who undergo total knee arthroplasty (TKA). KSS has been translated and validated into many languages but not Persian. The aim of this study was to translate and evaluate the validity and reliability of the Persian version of the new KSS., Methods: The Persian version of the new KSS was translated and culturally adapted according to international guidelines, including translation, back-translation, pre-testing, and expert committee review. A total of 142 patients scheduled to undergo TKA were included in this study and were asked to complete the Persian-KSS, Oxford Knee Score (OKS), and the Visual Analogue Scale (VAS) index both two weeks before the surgery and 6 months after the surgery. Face, content, and construct validity were evaluated to assess the validity of Persian-KSS., Results: The Persian-KSS was comprehensive, indicating that the Persian version of KSS was clear and easy to understand for Persian-speaking patients undergoing TKA. The reliability of the Persian-KSS, assessed by Cronbach's alpha, was 0.894 and 0.800 for the pre- and post-operative stages, respectively. The intraclass correlation coefficient (ICC) assessed the test-retest reliability, which was 0.766 and 0.796 for the pre- and post-operative stages, respectively. The construct validity analysis of Persian-KSS demonstrated a statistically significant correlation between Persian-KSS and the OKS (r = - 0.935, p-value = 0.000 for the pre-operative stage, and r = - 0.809, p-value = 0.000 for the post-operative stage) and VAS index (r = - 0.401, p-value = 0.001 for the pre-operative stage and r = - 0.259, p-value = 0.029 for the post-operative stage)., Conclusion: The Persian-KSS, developed after the translation and cross-cultural adaptation process, was proven to be a reliable and valid assessment measure for those who undergo TKA., (© 2023. The Author(s).)

Today, biologic prodrugs have led to targeting specific tumor markers and have increased specificity and selectivity in cancer therapy. Various studies have shown the role of ncRNAs in cancer pathology and tumorigenesis and have suggested that ncRNAs, especially miRNAs, are valuable molecules in understanding cancer biology and therapeutic processes. Most miRNAs-based research and treatment are limited to chemically synthesized miRNAs. Synthetic alterations in these miRNA mimics may affect their folding, safety profile, and even biological activity. However, despite synthetic miRNA mimics produced by automated systems, various carriers could be used to achieve efficient production of bioengineered miRNAs through economical microbial fermentation. These bioengineered miRNAs as biological prodrugs could provide a new approach for safe therapeutic methods and drug production. In this regard, bioengineered chimeric miRNAs could be selectively processed to mature miRNAs in different types of cancer cells by targeting the desired gene and regulating cancer progression. In this article, we aim to review bioengineered miRNAs and their use in cancer therapy, as well as offering advances in this area, including the use of chimeric tRNA/pre-miRNAs., (© 2023 American Institute of Chemical Engineers.)

Background: Recent changes in dietary habits have resulted in increased intake of advanced glycation end products (AGEs), which are known to have a predominant contribution to the pathogenesis and complications of coronary artery disease (CAD). AGEs are also thought to induce weight gain by affecting appetite, energy expenditure, and brown adipose tissue (BAT). Here, we investigated whether the restriction of dietary AGEs could affect appetite, body composition, anthropometric indices, and BAT-derived markers in CAD patients treated with angioplasty., Materials and Methods: Forty-two stented CAD patients were randomly allocated into two groups that received either a low-AGEs or a control diet for 12 weeks. At baseline and postintervention, fasting blood samples were analyzed for total AGEs, nesfatin-1, and BAT-derived markers (fibroblast growth factor 21 and neuregulin 4). Subjective appetite ratings and body composition were evaluated using the Visual Analog Scale (VAS) and bioelectric impedance analysis. Anthropometric indices, including fat mass index (FMI), abdominal volume index (AVI), and body adiposity index (BAI), were calculated through the relevant formula., Results: Restricting dietary AGEs for 12 weeks could cause a significant reduction in weight, FMI, AVI, and BAI ( P < 0.05) compared to the comparison group. In addition, VAS data analyses indicated a significant decrease in the sense of hunger and prospective food intake ( P < 0.05) in the intervention group compared to the comparison group. No significant difference was seen in the measured biochemical markers between the two groups., Conclusion: This study indicated that the low-AGEs diet could decrease appetite, weight, and anthropometric indices in stented CAD patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Research in Medical Sciences.)

Background: Acute submassive a massive pulmonary embolism are known as leading causes of cardiovascular morbidity and mortality in emergency departments. Choosing the optimal type of catheter directed thrombolysis (CDT) for treatment of pulmonary embolism presents a quandary to the practitioners. To the best of our knowledge, there is no meta-analysis comparing superiority of conventional CDT and ultrasound-accelerated catheter directed thrombolysis (USACDT). Therefore, in this meta-analysis, we aimed to compare conventional CDT with USACDT regarding clinical outcomes and safety profile., Methods: A systematic literature search of previous published studies comparing conventional CDT with USACDT regarding clinical outcomes and safety profile was carried out in the electronic databases including MEDLINE, Scopus, EBSCO, Google Scholar, Web of Science, and Cochrane from inception to December 2021. Data were analyzed by comprehensive meta-analysis software (CMA, version 3)., Results: The meta-analysis included nine studies with a total of 705 patients. Our meta-analysis showed that there is no significant difference between two groups with respect to pulmonary arterial systolic pressure (SMD: -0.084; 95% CI: -0.287 to 0.12; p : 0.41), RV/LV (SMD: -0.003; 95% CI: -0.277 to 0.270; p : 0.98), and Miller score (SMD: -0.345; 95% CI: -1.376 to 0.686; p : 0.51). Similarly, we found no statistically significant differences between two groups regarding major and minor bleeding ( p > .05)., Conclusion: Our meta-analysis showed that when compared with USACDT, conventional CDT provides similar clinical and hemodynamic outcomes or safety for treatment of pulmonary embolism without the need for very expensive technologies. However, randomized clinical trials are required to further investigate cost-effectiveness of USACDT in comparison with conventional CDT.

Tramadol (TRA) causes neurotoxicity whereas trimetazidine (TMZ) is neuroprotective. The potential involvement of the PI3K/Akt/mTOR signaling pathway in the neuroprotection of TMZ against TRA-induced neurotoxicity was evaluated. Seventy male Wistar rats were divided into groups. Groups 1 and 2 received saline or TRA (50 mg/kg). Groups 3, 4, and 5 received TRA (50 mg/kg) and TMZ (40, 80, or 160 mg/kg) for 14 days. Group 6 received TMZ (160 mg/kg). Hippocampal neurodegenerative, mitochondrial quadruple complex enzymes, phosphatidylinositol-3-kinases (PI3Ks)/protein kinase B levels, oxidative stress, inflammatory, apoptosis, autophagy, and histopathology were evaluated. TMZ decreased anxiety and depressive-like behavior induced by TRA. TMZ in tramadol-treated animals inhibited lipid peroxidation, GSSG, TNF-α, and IL-1β while increasing GSH, SOD, GPx, GR, and mitochondrial quadruple complex enzymes in the hippocampus. TRA inhibited Glial fibrillary acidic protein expression and increased pyruvate dehydrogenase levels. TMZ reduced these changes. TRA decreased the level of JNK and increased Beclin-1 and Bax. TMZ decreased phosphorylated Bcl-2 while increasing the unphosphorylated form in tramadol-treated rats. TMZ activated phosphorylated PI3Ks, Akt, and mTOR proteins. TMZ inhibited tramadol-induced neurotoxicity by modulating the PI3K/Akt/mTOR signaling pathways and its downstream inflammatory, apoptosis, and autophagy-related cascades.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms including impairment in social communication and restrictive and repetitive behaviors and interests. Music has emerged in the past decade as an intervention therapy for children with ASD. The aim of the present study was to evaluate the effects of music on cognition impairments in the valproic acid (VPA) rat model of autism. The VPA was administered for animal modeling of autism on embryonic day 12.5 (E12.5) (600 mg/kg). Male and female pups were sub divided into four main groups (Saline.Non-music, VPA.Non-music, Saline.Music, and VPA.Music). The rats in the music groups were exposed to Mozart's piano sonata K.448 for 30 days (4 h/day), from postnatal day (PND) 21 to 50. Autistic-like behaviors were tested using a social interaction, the Morris water maze (MWM), and a passive avoidance tasks at the end of the PND 50. Our results demonstrated that VPA-exposed rat pups had significantly lower sociability and social memory performance compared with the saline-exposed rats in both sexes. VPA-exposed rat pups exhibited learning and memory impairments in the MWM and passive avoidance tasks. Our results demonstrated that music improved sociability in VPA-exposed rats, especially in males. Furthermore, our findings revealed that music improved learning impairments in VPA-exposed male rats in MWM task. In addition, music improved spatial memory impairments in VPA-exposed rats of both sexes. We also found that music improved passive avoidance memory impairments in VPA-exposed rats of both sexes, especially in females. More investigation in future studies are needed., (© 2023 International Society for Developmental Neuroscience.)

This study examines whether the socio-demographic factors and cognitive sign features can be used for envisaging safety signs comprehensibility using predictive machine learning (ML) techniques. This study will determine the role of different machine learning components such as feature selection and classification to determine suitable factors for safety construction signs comprehensibility. A total of 2310 participants were requested to guess the meaning of 20 construction safety signs (four items for each of the mandatory, prohibition, emergency, warning, and firefighting signs) using the open-ended method. Moreover, the participants were asked to rate the cognitive design features of each sign in terms of familiarity, concreteness, simplicity, meaningfulness, and semantic closeness on a 0-100 rating scale. Subsequently, all eight features (age, experience, education level, familiarity, concreteness, meaningfulness, semantic closeness, and simplicity) were used for classification. Furthermore, the 14 most popular supervised classifiers were implemented and evaluated for safety sign comprehensibility prediction using these eight features. Also, filter and wrapper methods were used as feature selection techniques. Results of feature selection techniques indicate that among the eight features considered in this study, familiarity, simplicity, and meaningfulness are found to be the most relevant and effective components in predicting the comprehensibility of selected safety signs. Further, when these three features are used for classification, the K-NN classifier achieves the highest classification accuracy of 94.369% followed by medium Gaussian SVM which achieves a classification accuracy of 76.075% under hold-out data division protocol. The machine learning (ML) technique was adopted as a promising approach to addressing the issue of comprehensibility, especially in terms of determining factors affecting the safety signs' comprehension. The cognitive sign features of familiarity, simplicity, and meaningfulness can provide useful information in terms of designing user-friendly safety signs., (© 2023. The Author(s).)

Background: Hypercalciuria is one of the most important urinary risk factors in kidney stone formers. This study aimed to delineate the interaction of some demographic, serum, and urinary risk factors influencing 24-h urinary (24-U) calcium excretion., Methods: This study was secondary data analysis, using data from 593 kidney stone patients referred to the Labbafinejad kidney stone prevention clinic from March 2015 to May 2019. The study considered serum, urinary and demographic factors that interact to influence 24-U calcium using path analysis. In addition to the direct impact of predictors on the 24-U calcium, this analysis considered the effects of the predictors on the 24-U calcium transmitted by a mediating variable named indirect effects., Results: The results showed that age indirectly affected on 24-U calcium through 25-hydroxy vitamin D (25(OH)D), serum and 24-U creatinine. As well, weight had an indirect effect through 24-urine metabolites (creatinine, citrate, urea, and sodium). Among serum variables, PTH and creatinine significantly directly affected on 24-U calcium. In comparison, 25(OH)D and phosphorus appeared to influence 24-U calcium indirectly through serum parathormone. Regarding 24-U metabolites, sodium, urea, and citrate had a significant direct effect on 24-U calcium. Moreover, 24-U creatinine has a significant direct and indirect effect on 24-U calcium through citrate and urea as mediator variables., Conclusion: Serum 25(OH)D and phosphorus, along with age and weight, indirectly affected urinary calcium through a third variable. Other variables (PTH, serum creatinine, and 24-U sodium, urea, and citrate) showed a direct effect on 24-U calcium excretion., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: This study examined the short-term effect of motivational interviewing on treatment adherence and self-efficacy of adolescents with asthma., Design: The randomized controlled trial., Method: In this study, 72 adolescents with asthma were recruited and assigned to experimental and control groups randomly. In the experimental group, the motivational interviewing was performed for five weekly sessions lasting 80-90 min. The treatment adherence and self-efficacy questionnaires were completed before the intervention, 2 weeks and 3 months after the intervention in both groups. Data were analysed by Chi-Square test, independent samples T-test, repeated measures of Wilcoxon and generalized estimating equation., Results: The treatment adherence was found to be significantly higher 2 weeks (p = 0.006) and 3 months after the intervention (p = 0.04) in the experimental group than the control group. In addition, the degree of self-efficacy was significantly more in the experimental group 2 weeks (p < 0.001) and 3 months later (p < 0.001) than the control group. The result of generalized estimating equation showed that the intervention group had an average of 14.44 more self-efficacy points than the control group (p < 0.001). Also, treatment adherence in the intervention group was significantly higher than the control group (β = 6.14, p = 0.05(., Conclusion: This study adds to the evidence for the effectiveness of motivational interviewing in treatment of adolescents with asthma., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: Neuregulin-4 (Nrg4), a novel brown fat-enriched factor, has been reported to play a crucial role in developing metabolic disorders. The current case-control study aimed to investigate the association between serum Nrg4 and coronary artery disease (CAD)., Methods: This study enrolled 43 patients with CAD and 43 subjects with normal coronary arteries diagnosed by coronary angiography. Anthropometric and biochemical parameters were measured and recorded. The serum Nrg4 level was determined using the enzyme-linked immunosorbent assay. The relationships between circulating Nrg4 and CAD and other clinical parameters were analyzed. A receiver operating characteristic analysis was applied to assess the utility of Nrg4 in identifying CAD., Results: The study population comprised 86 patients, including 64 men (74.4%), at a mean age of 57.83±6.01 years. Patients with CAD had significantly lower serum Nrg4 than the control group (P<0.001). The serum Nrg4 level was negatively correlated with anthropometric variables, including the body mass index, waist circumference, and the waist-to-hip ratio, fasting blood glucose, and the triglyceride-glucose index (P<0.05). In multivariable-adjusted regression analysis, the odds of CAD decreased by 46% per 1 SD elevation in the serum Nrg4 level (OR, 0.54; 95% CI, 0.40 to 0.73; P<0.001) after controlling for potential confounders. Nrg4 showed a significantly high area under the curve value (AUC, 0.85; 95% CI, 0.75 to 0.94) with 81.4% sensitivity and 95.3% specificity to identify CAD., Conclusion: Generally, the serum level of Nrg4 declines in patients with CAD, which might be an independent risk factor for CAD., (Copyright© 2023 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behavior. Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R). In this study, the effects of ciproxifan (CPX) (1 and 3 mg/kg, intraperitoneally) on cognitive impairments in rat pups exposed to valproic acid (VPA) (600 mg/kg, intraperitoneally) wereexamined on postnatal day 48-50 (PND 48-50) using marble-burying task (MBT), open field, novel object recognition (NOR), and Passive avoidance tasks. Famotidine (FAM) (10, 20, and 40 mg/kg, intraperitoneally) was also used to determine whether histaminergic neurotransmission exerts its procognitive effects via H2 receptors (H2Rs). Furthermore, a histological investigation was conducted to assess the degree of degeneration of hippocampal neurons. The results revealed that repetitive behaviors increased in VPA-exposed rat offspring in the MBT. In addition, VPA-exposed rat offspring exhibited more anxiety-like behaviors in the open field than saline-treated rats. It was found that VPA-exposed rat offspring showed memory deficits in NOR and Passive avoidance tasks. Our results indicated that 3 mg/kg CPX improved cognitive impairments induced by VPA, while 20 mg/kg FAM attenuated them. We concluded that 3 mg/kg CPX improved VPA-induced cognitive impairments through H3Rs. The histological assessment showed that the number of CA1 neurons decreased in the VPA-exposed rat offspring compared to the saline-exposed rat offspring, but this decrease was not significant. The histological assessment also revealed no significant differences in CA1 neurons in VPA-exposed rat offspring compared to saline-exposed rat offspring. However, CPX3 increased the number of CA1 neurons in the VPA + CPX3 group compared to the VPA + Saline group, but this increase was not significant. This study showed that rats prenatally exposed to VPA exhibit cognitive impairments in the MBT, open field, NOR, and Passive avoidance tests, which are ameliorated by CPX treatment on PND 48-50. In addition, morphological investigations showed that VPA treatment did not lead to neuronal degeneration in the CA1 subfield of the hippocampus in rat pups., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This study assesses the protective effects of astaxanthin (AST) against vitrification/warming-induced cryoinjuries of ovarian tissue slices in sheep. Cortical slices of slaughterhouse acquired-ovine ovaries were randomly distributed in different groups: fresh, toxicity, and five vitrification groups including vitrification in presence of 0 (control group), 1, 10 and 100 μM astaxanthin or 100 μM vitamin E. After vitrification/warming and 24 h culturing, the samples were subjected to histological studies, antioxidant evaluation by TAC and TBAR assays, and assessment of relative expression of BMP4, BMP15, GDF9 and KITLG genes related to folliculogenesis and follicular growth regulation. According to the results, vitrification reduced the percentage of morphologically intact follicles compared to the fresh and toxicity groups (p < 0.05). In vitrification groups, vitamin E and all three concentrations of AST increased the percentage of intact pre-antral follicles and antioxidant activity relative to the vitrified control (p < 0.05). This enhancement significantly occurred in 10 μM AST group more than vitamin E (p < 0.05). Also, 10 μM concentration of AST enhanced the expression of all the examined genes compared to the control (p < 0.05), while the expression of BMP4, BMP15 and KITLG was higher in the AST than vitamin E (p < 0.05). The latter could increase only the expression of GDF9 compared to the control group (p = 0.011). In conclusion, AST is a highly effective antioxidant for maintaining the survival of pre-antral follicles, retaining cell density, increasing total antioxidant capacity, and increasing the expression of some genes related to follicular development after short-term culture of vitrified/warmed ovarian tissue slices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The impact performance and compression after impact characteristics of 2D and 3D fiber metal laminates (FMLs) are investigated both experimentally and numerically. Commercial-grade GLARE3A-3/2-0.3, and a recently developed FML, which incorporates a unique 3D glass fabric, are used in the study. Both FMLs have similar areal densities. The specimens are subjected to impact loading at three energy levels-low, intermediate, and high. The test results indicate that GLARE is slightly more resilient under impact compared to the 3DFML. However, since GLARE is much thinner than the 3DFML, the two-material systems exhibit very different failure modes. GLARE and 3DFML lost up to 62.6% and 41.5% of their original compressive load-bearing capacity, respectively. Robust and accurate finite element models are developed that can predict the damage evolution and failure modes of both FMLs. Knowing the level of reduction in the residual load-bearing capacity of a material resulting from an impact is of practical importance when assessing the service life of materials. However, further exploration would be required to determine how the information obtained through testing relatively small-sized specimens in a laboratory environment can be extrapolated to larger real-life structural components.

Background: Insulin resistance (IR), even in its subclinical state, is a significant risk factor for the onset and progression of coronary artery disease (CAD). IR is a multifactorial condition, and dietary composition is a factor associated with its development. Elevated advanced glycation end products (AGEs) in the body, secondary to highly processed food consumption, can impair glucose metabolism. The present study investigated whether a restricted AGE diet could affect insulin sensitivity and anthropometric indices reflecting visceral adipose tissue in nondiabetic CAD patients., Methods: This trial randomly allocated 42 angioplasty-treated patients to follow either low-AGE or control diets based on the AHA/NCEP guidelines for 12 weeks. Serum levels of total AGEs, insulin, HbA1c, and fasting blood sugar, as well as anthropometric measurements, were evaluated before and after the intervention. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and anthropometric indices were calculated according to the proposed formula. The patients' health status was assessed using the Seattle Angina Questionnaire (SAQ) at baseline and after the intervention., Results: Our study showed a significant reduction in anthropometric indices in the low-AGE group after 12 weeks. Insulin levels and IR decreased during the low-AGE diet. No significant changes were observed in the other serum biochemical markers. All SAQ domains significantly decreased in both groups, except for Treatment Satisfaction., Conclusion: A low-AGE diet for 12 weeks had beneficial effects on HOMA-IR and insulin levels in patients with CAD. Regarding the fundamental role of AGE in IR development and body fat distribution, AGE restriction may positively affect these patients., (Copyright © 2023 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

MicroRNA-140 (miR-140) acts as a tumor suppressor and plays a vital role in cell biological functions such as cell proliferation, apoptosis, and DNA repair. The expression of this miRNA has been shown to be considerably decreased in cancer tissues and cell lines compared with normal adjacent tissues. Consequently, aberrant expression of some miR-140 target genes can lead to the initiation and progression of various human cancers, such as breast cancer, gastrointestinal cancers, lung cancer, and prostate cancer. The dysregulation of the miR-140 network also affects cell proliferation, invasion, metastasis, and apoptosis of cancer cells by affecting various signaling pathways. Besides, up-regulation of miR-140 could enhance the efficacy of chemotherapeutic agents in different cancer. We aimed to cover most aspects of miR-140 function in cancer development and address its importance in different stages of cancer progression., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Long non-coding ribonucleic acids (LncRNAs) are recently known for their role in regulating gene expression and the development of cancer. Controversial results indicate a correlation between the tissue expression of LncRNA and LncRNA content of extracellular vesicles. The present study aimed to evaluate the expression of different LncRNAs in non-small cell lung cancer (NSCLC) patients in tumor tissue, adjacent non-cancerous tissue (ANCT), and exosome-mediated lncRNA. Tumor and ANCT, as well as serum samples of 168 patient with NSCLC, were collected. The GHSROS, HNF1A-AS1, HOTAIR, HMlincRNA717, and LINCRNA-p21 relative expressions in tumor tissue, ANCT, and serum exosomes were evaluated in NSCLC patients. Among 168 NSCLC samples, the expressions of GHSROS (REx = 3.64, p = 0.028), HNF1A-AS1 (REx = 2.97, p = 0.041), and HOTAIR (REx = 2.9, p = 0.0389) were upregulated, and the expressions of HMlincRNA717 (REx = −4.56, p = 0.0012) and LINCRNA-p21 (REx = −5.14, p = 0.00334) were downregulated in tumor tissue in contrast to ANCT. Moreover, similar statistical differences were seen in the exosome-derived RNA of tumor tissues in contrast to ANCT samples. A panel of the five lncRNAs demonstrated that the area under the curve (AUC) for exosome and tumor was 0.937 (standard error: 0.012, p value < 0.0001). LncRNAs GHSROS, HNF1A-AS1, and HOTAIR showed high expression in tumor tissue and exosome content in NSCLC, and a panel that consisted of all five lncRNAs improved diagnosis of NSCLC.

Wireless sensor networks (WSNs) are considered part of an environmentally friendly technology leading to more timely and cost-effective production and management of farms. Despite the potential of WSNs to agricultural development in the global South, outreach is still very limited, also in Iran. Therefore, in order to facilitate the adoption of WSNs, it is necessary to identify the factors influencing and challenging the adoption of this technology. This exploratory study uses a qualitative approach to identify the main barriers WSN outreach is facing. In the results, we distinguish facts that we define as issues or barriers that were identified by others from fears that are not supported by evidence so far, at the level of the farmers, the government actors as well as the technology itself. Facts include communication barriers such as internet access, farmers' knowledge levels and rigidity to change as well as the government's top-down organisation of the extension programme and support levels. Fears are mainly expressed on the technology itself and relate to costs, a lack of access, the complexity of use and reliability of the data. We provide a nuanced view of how fears need to be acknowledged and facts are to be tackled., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Taheri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Saline environments are largely unexplored sources of actinomycetes with the potential to produce biologically active secondary metabolites. A total of 34 actinomycete isolates from water, sediments and mostly rhizosphere (82%) were collected from different sites at Howz Soltan Lake in Iran. Based on phylogenetic analysis, the isolates belonged to the genera Streptomyces, Nocardia and Saccharomonospora. Cytotoxic assay revealed extract from isolate act9 as the most potent (19.716±5.72 µg/ml) against the MDA-MB-231 human breast cancer cell. Also, 38% of the isolates showed antimicrobial activity against some of the test microorganisms. The ethyl-acetate extract of isolate act18 showed the strongest antibacterial effect against Staphylococcus aureus and MRSA, and was further analyzed by GC/MS. Ar-tumerone (26.41%) and butyl isodecyl phthalate (21.77 %) were the main constituents detected in the extract. This is the first time Ar-tumerone is being detected in a prokaryote. Isolate act18 showed a high 16S rRNA sequence similarity to that of Streptomyces youssoufiensis DSM 41920. In addition, a number of the isolates produced different enzymes including lipase, amylase, protease, gelatinase, urease and lecithinase. Some of the isolates belonging to the genera Streptomyces and Nocardia exhibited plant growth promoting activity such as increased seed germination, stem length and the number of Echium leaves during the 20 days. Findings from this study indicated the diversity and biosynthetic potential of actinomycetes from saline environment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In today's hyper-competitive marketplace, the crucial role of the sustainability concept has been highlighted more. Hence, managers' attention has been attracted to the concept of sustainable supply chains. On the other hand, after the COVID-19 outbreak, the importance of medical devices and their demand has drastically enhanced, which has led to shifting the attention of researchers toward this industry. In this regard, based on the importance of the mentioned points, the current study configures a sustainable supply chain network for the medical devices industry. In this way, given the crucial role of the oxygen concentrator during the COVID-19 outbreak, the present study investigates the supply chain of the mentioned goods as a case study. Also, this research develops an efficient hybrid solution method based on goal programming, a heuristic algorithm, and the simulated annealing algorithm to solve the suggested model. Eventually, sensitivity analysis is conducted to examine the influence of the crucial parameters of the model on the outputs, and managerial insights are provided. According to the achieved results, the suggested model and the developed hybrid method demonstrate a good performance which shows their efficiency., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hazardous material road transportation is one of the most challenging procedures performed by large trucks and trailers. In this study, after examining and analyzing road hazardous material transportation accidents, occurred over 5 years in Iran, the contributing factors of road hazardous material transportation accidents were determined. Subsequently, the introduced factors were prioritized using fault tree analysis and the Dempster-Shafer evidence theory. The results revealed that the frequency of accidents has significantly increased in recent years. It is shown that the three pivotal factors in road hazardous material transportation accidents were transport vehicle, packaging and loading of hazardous materials, and human factors. These findings provide an empirically supported theoretical basis for transportation corporations to take corrective and preventative measures to reduce the accident risks. A novel technique has been introduced for analyzing the causes of road hazardous material transportation accidents. Finally, the absence of hazardous material transportation companies in Iran is introduced as a critical reason for the higher frequency of such accidents in Iran compared to other countries.

Traffic accidents are considered a major public health problem in many countries. The aim of this study was to explore the relationships between traffic climate factors (i.e., external affective demands, functionality and internal requirements), driver behaviours, dangerous driving behaviours and traffic accident involvement among taxi drivers. A total of 450 male taxi drivers participated in the study. The traffic climate scale (TCS), the driver behaviour questionnaire (DBQ), the positive driver behaviours scale (PDBS) and the Dula dangerous driving index (DDDI) were used to measure driving behaviours and traffic conditions. The results showed that there was a significant negative correlation between functionality (of the TCS) and the number of accident involvement. Further analysis demonstrated that the effect of risky driving (of the DDDI) on accident involvement was significant. Taken together, these findings suggest that functional traffic systems and driving environments play important roles in traffic accident involvement.

Rationale: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and cognitive behaviors. Histamine H3 receptor (H3R) antagonists are considered as therapeutic factors for treating cognitive impairments., Objectives: The aim of the present study was to evaluate the effects of the H3R antagonist, ciproxifan (CPX), on cognition impairment especially, spatial learning memory, and synaptic plasticity in the CA1 region of the hippocampus in autistic rats., Methods: Pregnant rats were injected with either valproic acid (VPA) (600 mg/kg, i.p.) or saline on an embryonic day 12.5 (E12.5). The effects of the H3R antagonist, ciproxifan (CPX) (1, 3 mg/kg, i.p.), were investigated on learning and memory in VPA-exposed rat pups and saline-exposed rat pups using Morris water maze (MWM) and social interaction tasks. The H2R antagonist, famotidine (FAM) (10, 20, 40 mg/kg, i.p.), was used to determine whether brain histaminergic neurotransmission exerted its procognitive effects through the H2R. In addition, synaptic reinforcement was evaluated by in vivo field potential recording., Results: The results showed that VPA-exposed rat pups had significantly lower sociability and social memory performance compared to the saline rats. VPA-exposed rat pups exhibited learning and memory impairments in the MWM task. In addition, VPA caused suppression of long-term potentiation (LTP) in the CA1 area of the hippocampus. Our results demonstrated that CPX 3 mg/kg improved VPA-induced cognitive impairments and FAM 20 mg/kg attenuated cognitive behaviors as well as electrophysiological properties., Conclusions: CPX 3 mg/kg improved VPA-induced impairments of LTP as well as learning and memory deficits through H2R., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients. This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES). Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130&#95;131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN. Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes.

Excitotoxicity and oxidative stress are central to the pathology of the nervous system, and inhibition of excitotoxicity induced by glutamate is one of the therapeutic goals determined for stroke. The present study aimed to investigate the effects of Astaxanthin, a potent natural antioxidant, on complications caused by acute cerebral stroke. In this research, 60 male Wistar rats were used which were divided into 5 groups as follow: (1) the sham group (vehicle), (2) the ischemic control group (vehicle), and the ischemic groups treated by Astaxanthin with doses of 25, 45, and 65 mg/kg. In the ischemic groups, ischemic model was performed by middle cerebral artery occlusion (MCAO) method, and the Astaxanthin administration was carried out after the artery occlusion and before opening the artery. The obtained results indicated that Astaxanthin could significantly reduce stroke volume, neurological deficits, and lipid peroxidation. Moreover, it was able to restore total oxidant status (TOS) and caspase 3 level to the normal level. The activity of antioxidant enzyme glutathione peroxidase (GPX), and the expression of catalase, GPx and nuclear factor kappa B (NFκb) genes, which were reduced after ischemia, were increased. This phenomenon was particularly pronounced for glutamate transporter 1 (GLT-1). Furthermore, Astaxanthin decreased the augmented pro-apoptotic gene Bax and restored the reduced Bcl2 expression to the normal level. Significant effects on the P53 and PUMA expression were not observed. Overall, the medium dosage of Astaxanthin appears to be more effective in reducing the complications of ischemia, particularly on our major study endpoints (stroke volume and neurological defects). Longer studies with a more frequent administration of Astaxanthin are required to better understand the precise mechanism of Astaxanthin., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A quick literature search reveals the significant lack of data and information concerning magnesium-to-magnesium bonded joints as well as fiber-metal laminates (FMLs) made with magnesium alloys. Therefore, a systematic series of experimental and numerical investigations are carried out to assess the performance of single-lap joints mating FML adherends. The primary goal is to better understand the effects of geometrical and material parameters that influence the performance of magnesium-to-magnesium joints. The FML adherends used in this study consist of basalt natural fiber-epoxy laminate sandwiched in between thin sheets of magnesium alloys, which were subsequently adhesively bonded using a room-cured epoxy resin. The effects of two types of surface treatments, namely, "sandblasting" and "sandblasting with resin coating" on the bond strength and failure mechanism of the adhesively bonded joints (ABJs) are investigated. A 3D numerical model developed to simulate the response of the joints subjected to quasi-static lap-shear tests. This model, which accounts for the material and geometrical nonlinearity in the joints, is used to perform a parametric analysis for establishing the optimal overlap bond length. The distributions of the shear and peel stresses in the overlap region and the effects of adhesive thickness on the performance of the joints are systematically examined. The comparison of the experimental data and numerical results confirms the robustness and cost-effectiveness of the numerical model in predicting the response of such single-lap ABJs., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Familial combined hyperlipidemia (FCHL) is one of the most common familial lipoprotein disorders of the lipoproteins, with a prevalence of 0.5% to 2% in different populations. About 10% of these patients suffer from cardiovascular disease and this number is increased by up to 11.3% in the young survivors of myocardial infarction and by 40% among all the survivors of myocardial infarction. Although initially thought to be that FCHL has an inheritance pattern of monogenic, the disease's etiology is still not fully understood and it appears that FCHL has a complex pattern related to genetic variants, environmental factors, and lifestyles. Two strategies have been used to identify its complex genetic background: candidate gene and the linkage approach, which have yielded an extensive list of genes associated with FCHL with a variable degree of scientific evidence. Until now, more than 30 different genetic variants have been identified related to FCHL. In this study, we aimed to review the individual genes that have been described in FCHL and how these genes and variants can be related to the current concept of metabolic pathways resulting in familial combined hyperlipidemia., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Fentanyl and midazolam are popular drugs for sedation and analgesia in intensive care unit. Gabapentin has sedative and analgesic effects, as well. Our purpose was to study gabapentin addition to fentanyl and midazolam to reach the target sedation level in patients requiring mechanical ventilation., Methods: This was a randomized and double-blinded trial. Fifty patients receiving mechanical ventilation and aged from 18 to 70 years were randomized 1 : 1 to 300 mg gabapentin q8hr or placebo. The initial infusion rates of fentanyl and midazolam were 1-2 µg kg-1 h-1 and 0.06-0.2 mg kg-1 h-1, respectively, in both groups. Treatments continued prior to weaning. Ramsay sedation scale score (2-3) and behavioral pain scale score (≤4) were used for the evaluation of sedation and analgesia levels, respectively., Results: A total of 43 patients were studied. Both treatment modalities reached the target sedation and analgesia levels. In the intervention group, there were significant reductions in daily consumption of fentanyl and midazolam (P < .01). Duration of ventilation was shorter in the intervention group (4.1 ± 1.7 days vs 5.1 ± 1.3 days, P > .05). There was no significant difference in intensive care hospitalization, although it was shorter in the intervention group (201 ± 24 hours vs 224 ± 19 hours, P > .05)., Conclusions: This trail showed that both treatment modalities could reach target sedation and analgesia levels without significant differences. Add-on therapy with gabapentin could reduce the total dose of fentanyl and midazolam.

Background: Recent in vitro and clinical studies have shown that ultrasound-accelerated catheter-directed thrombolysis (USACDT) can accelerate thrombolysis. Therefore, in this meta-analysis, we aimed to compare the efficacy and safety of USACDT with conventional catheter-directed thrombolysis in patients with deep vein thrombosis., Methods: A systematic search of the following electronic databases was performed from their dates of inception to 20 June 2020: MEDLINE, Scopus, Google Scholar, CINAHL, Cochrane Library, and EMBASE. All randomized controlled trials that directly compared the complications and efficacy of USACDT and conventional catheter-directed thrombolysis in patients with deep vein thrombosis were identified. The statistical analysis was performed using comprehensive meta-analysis software., Results: Finally, 18 studies with a total of 597 participants were included in our meta-analysis according to the eligibility criteria. Pooled proportion of USACDT success in patients with deep vein thrombosis was 87.8% (18 studies; 95% CI: 83.1-91.3). Success rate was significantly higher in USACDT treatment than in conventional catheter-directed thrombolysis treatment (seven studies; OR: 2.96; 95% CI: 1.69-5.16; P  < 0.01)). Although the mean infusion time was higher in catheter-directed thrombolysis treatment compared to USACDT treatment, this difference was not statistically significant (three studies; MD: -1.46; 95% CI: -3.25-0.32; P  = 0.10). Moreover, pooled rate of complications was lower in USACDT than catheter-directed thrombolysis which was not statistically significant (seven studies; OR: 0.49; 95% CI: 0.13-1.76; P  = 0.27)., Conclusion: This meta-analysis revealed that USACDT significantly increased the success rate of thrombolysis compared to conventional catheter-directed thrombolysis. Furthermore, USACDT was associated with lower rate of complication and infusion time. Taken together, these findings confirm the superiority of this novel intervention over conventional catheter-directed thrombolysis in treatment of patients with deep vein thrombosis.

Background: This study aimed to investigate the relationship between depression and pain anxiety with pain catastrophizing in patients with coronavirus disease 2019 (COVID-19)., Methods: In this descriptive, correlational study, 180 patients with COVID-19 in Akhtar and Imam Hossein hospitals in Tehran, Iran, were included from March 2019 to April 2020. All participants completed three questionnaires, including the Pain Catastrophizing Scale (PCS), Pain Anxiety Symptoms Scale (PASS), and Beck's Depression Inventory (BDI). The data were analyzed using Pearson correlation coefficient and multivariate regression., Results: There was a positive and significant relationship between the dimensions of rumination, magnification, and helplessness with total score of pain catastrophizing, as well as moderate to severe dimensions with total pain anxiety and depression in patients with COVID-19., Conclusions: According to the results of regression analysis, pain anxiety based on pain catastrophizing dimensions was statistically significant, so that rumination, magnification, and helplessness could predict pain anxiety and explain a total of 15.1% of changes in pain anxiety. Also, depression was statistically significant based on dimensions of pain catastrophizing, so rumination, magnification, and helplessness could predict the patients' depression and explain 13.6% of depression changes., Competing Interests: Conflict of Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022, Author(s).)

Efferocytosis has a critical role in maintaining tissues and organs' homeostasis by removing apoptotic cells. It is essential for human health, and disturbances in efferocytosis may result indifferent illnesses. In case of inadequate clearance of the dead cells, the content in the cells would be released. In fact, it induces some damages to the tissue and leads to the prolonged inflammation, so unsuitable phagocytosis of the apoptotic cells is involved in occurrence as well as expansion of numerous human chronic inflammatory diseases. Studies have shown age dependence of the neuro-degenerative diseases, which are largely due to the neuro-inflammation and the loss of neurons and thus cause the brain's functional disorders. Efferocytosis is coupled to anti-inflammatory responses that contribute to the elimination of the dying neurons in neuro-degenerative diseases, so its disruption may make a risk factor in numerous human chronic inflammatory diseases such as multiple sclerosis, Alzheimer's disease, glioblastoma, and Rett syndrome. This study is a review of the efferocytosis molecular pathways and their role in neuro-degenerative diseases in order to discover a new treatment option to cure patients., (© 2021. Fondazione Società Italiana di Neurologia.)

It has been more than a year since the outbreak of COVID-19, and it is still the most critical issue of the healthcare system. Discovering effective strategies to treat infected patients is necessary to decrease the mortality rate. This study aimed to determine the effects of nanocurcumin on the severity of symptoms and length of hospital stay (LOS) in COVID-19 patients. Forty-eight COVID-19 patients were randomly assigned into nanocurcumin (n = 24) and placebo (n = 24) groups receiving 160 mg/day nanocurcumin or placebo capsules for 6 days. Mean differences of O 2 saturation were significantly higher in patients who received nanocurcumin supplements (p = 0.02). Also, nanocurcumin treatment significantly reduced the scores of domains 3 and 4 and the total score of Wisconsin Upper Respiratory System Survey (WURSS-24), indicating milder symptoms in the treatment group (p = 0.01, 0.03, and 0.01 respectively). Besides, the LOS in curcumin groups was lower than in the placebo group, although the difference was not statistically significant (6.31 ± 5.26 vs. 8.87 ± 8.12 days; p = 0.416). CBC/differentiate, hs-CRP level and the pulmonary involvement in CT scan were not different between the two groups. As nanocurcumin can be effective in increasing O 2 saturation and reducing the severity of symptoms in COVID-19 patients, it could probably be used as a complementary agent to accelerate the recovery of patients., (© 2022 John Wiley & Sons Ltd.)

Background: Previous researchers examined the effects of either drivers' personal characteristics or traffic sign design features on the usability of traffic signs. Their research indicated a connection existed between personal characteristics and usability and between design features and usability., Objectives: The focus of this study was to investigate which personal characteristics of drivers and which features of traffic sign design affect traffic sign usability the most., Methods: The study was conducted in three stages. In the first stage, the participants filled out a questionnaire designed to record each driver's personal characteristics. In the second stage, a System Usability Scale (SUS) was used to evaluate the subjective usability of traffic signs. The SUS had 10 statements that participants (N = 386) scored on a 5-point Likert-type scale from strongly agree to strongly disagree. In the third stage, these participants assigned from 0 to 100 points to 20 signs based on participant perception of the five design features of familiarity, concreteness, simplicity, meaningfulness, and semantic distance., Results: The results showed that four of the five personal characteristics studied (age, education level, possession of a driving license, and formal driving experience) correlated significantly with traffic sign usability. The exception was gender, which did not correlate significantly. Additionally, it was found that the five traffic sign design features correlated in varying degrees of significance with each other and with specific traffic signs., Conclusions: Traffic sign usability depends mostly both on driver education level and age group and on the design feature of meaningfulness. These findings have implications for how drivers should be trained and how signs should be designed.