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Clinical manifestation and management of Remdesivir infiltration: a case series
Remdesivir is the first approved antiviral against severe acute respiratory syndrome coronavirus 2 (SARSCoV2) with a promising effect both on in-patient and out-patient settings. Regarding the acceleration program for the development of COVID-19 therapies and emergency use authorization, reporting new adverse events other than those mentioned in the first package inserts and beyond clinical trials is expected. Medication infiltration is one of the post-marketing reported remdesivir adverse events. The present study reported four new cases of remdesivir infiltration, their clinical courses, management, and outcomes. Moreover, all other reported cases were collected to identify event risk factors and provide recommendations for reducing the condition burden. All patients received non-pharmacological interventions and conservative therapy, which included aspiration, catheter removal, limb immobilization, non-occlusive dressing, and warm compresses. Intralesional triamcinolone acetonide was also administered for three cases. The remdesivir infusion continued through another intravenous line, and the event did not reoccur for the same patient. All patients recovered without sequels. The present study attempted to address all the factors that affect remdesivir infiltration and provide clinical recommendations to reduce the incidence and event burden. The principal step in prevention and successful management is staff education. After establishing staff instructions, event severity was significantly reduced in the studied center. Furthermore, non-pharmacological intervention and intralesional corticosteroid administration could prevent local reaction extension and could probably accelerate the healing process
Development of new nanofibrous nerve conduits by PCL-Chitosan-Hyaluronic acid containing Piracetam-Vitamin B12 for sciatic nerve: A rat model
Peripheral nerve injury is a critical condition that can disrupt nerve functions. Despite the progress in engineering artificial nerve guidance conduits (NGCs), nerve regeneration remains challenging. Here, we developed new nanofibrous NGCs using polycaprolactone (PCL) and chitosan (CH) containing piracetam (PIR)/vitamin B12(VITB12) with an electrospinning method. The lumen of NGCs was coated by hyaluronic acid (HA) to promote regeneration in sciatic nerve injury. The NGCs were characterized via Scanning Electron Microscopy (SEM), Fourier transform infrared (FTIR), tensile, swelling, contact angle, degradation, and drug release tests. Neuronal precursor cell line (PCL12 cell) and rat mesenchymal stem cells derived from bone marrow (MSCs) were seeded on the nanofibrous conduits. After that, the biocompatibility of the NGCs was evaluated by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, 4′,6-diamidino-2-phenylindole (DAPI) staining, and SEM images. The SEM demonstrated that PCL/CH/PIR/VITB12 NGCs had nonaligned, interconnected, smooth fibers. The mechanical properties of these NGCs were similar to rat sciatic nerve. These conduits had an appropriate swelling and degradation rate. The In Vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VITB12 NGCs towards PC12 cells and MSCs. The in vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VIT B12 NGCs towards MSCs and PC12 cells. To analyze functional efficacy, NGCs were implanted into a 10 mm Wistar rat sciatic nerve gap and bridged the proximal and distal stump of the defect. After three months, the results of sciatic functional index (55.3 ± 1.8), hot plate latency test (5.6 ± 0.5 s), gastrocnemius muscle wet weight-loss (38.57 ± 1.6 %) and histopathological examination using hematoxylin-eosin (H&E) /toluidine blue/ Anti-Neurofilament (NF200) staining demonstrated that the produced conduit recovered motor and sensory functions and had comparable nerve regeneration compared to the autograft that can be as the gold standard to bridge the nerve gaps
Development and Validation of a Clinical Guideline for Reproductive Health in Natural Disasters: A Mixed Methods Study
Background & aim: Preparing to deal with natural disasters, is important for the health of the society, and a valid clinical guideline which fits the country's conditions can lead to a reduction in complications caused by the aforementioned disasters. Therefore, the present study was conducted to develop and validate the clinical guidelines for reproductive health in natural disasters. Methods: This mixed methods study was carried out in three phases. The first phase was a structured review of literature which systematically reviewed the articles and clinical guidelines related to the reproductive health in disasters. In the second phase, a qualitative study was conducted with the content analysis approach in order to identify the needs related to women's reproductive health in disasters, and a draft clinical guide was prepared. In the third phase, the validation of the prepared draft was carried out by a group of experts using the (RAND) Research and Development technique. Results: The themes obtained included the consequences of facing a disaster and the need to provide comprehensive services. The clinical guideline consists of 5 chapters including an introduction on the importance of reproductive health in natural disasters, general clinical guidelines, prevention of physical and mental injuries in a crisis, access to reliable sources of information and the availability of the health services provider team. Conclusion: Correct management of crisis, empowering information skills and access to service providers in crises are of particular importance. Therefore, support of health care providers and training of service providers to learn about evidence-based performance in crises and their use is a necessary step to implement the clinical guidelines prepared in the country
Selenium mitigates methotrexate‐induced testicular injury: Insights from male NMRI mice model
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
The association between type 2 diabetes and dietary antioxidant index: a cross-sectional study in the Iranian population
Objective: This study aims to explore the association between dietary antioxidant index (DAI) and type 2 diabetes (T2D) in the Iranian population. Subjects and methods: The present cross-sectional study comprised 4,241 participants aged from 35 to 70. A food frequency questionnaire (FFQ) was used to assess dietary intake. The DAI score was determined using Wright’s method, which quantifies the antioxidant content of the diet. Logistic and linear regression analyses were used to determine the link between DAI and T2D after adjusting for confounding variables. Results: Negative associations were found between T2D with total score of DAI (OR = 0.67, CI95%: 0.55-0.81, P = 0.001) and DAI score of zinc (OR = 0.53, CI95%: 0.40-0.72, P = 0.001), manganese (OR = 0.77, CI95%: 0.68-0.88, P = 0.001), and selenium (OR = 0.88, CI95%: 0.78-0.98, P = 0.010) after adjustments for age, sex, BMI, education level, marital status, occupation, physical activity, and calorie intake. Conclusion: These results indicate the significance of an antioxidant-rich diet in preventing T2D and its complications. Nevertheless, additional investigation is required to validate these findings and explore the fundamental mechanisms of the association of T2D and dietary antioxidants
Exploring the anti-depressant effects and nitric oxide modulation of quercetin: A preclinical study in Socially Isolated mice
Objectives: This study investigates the effects of quercetin, an antioxidant and nitric oxide (NO) modulator, on depressive-like behaviours triggered by social isolation stress (SIS) in mice. SIS, known to harm psychosocial functioning and increase the risk of depression, involves oxidative stress and NO in its pathophysiology. Methods: 72 male mice were divided into nine groups, including the social (SC) group as the control group (stress-free with normal saline intake). The isolation (IC) groups received normal saline, quercetin at doses of 10, 20, and 40 mg/kg, the nitric oxide synthetase inhibitor L-NAME at a dose of 5 mg/kg, the NO precursor L-arginine at a dose of 100 mg/kg, an ineffective dose of quercetin combined with L-NAME and an effective dose of quercetin combined with L-arginine. Behavioural tests (open-field, forced swimming, and splash tests) were conducted, followed by measuring hippocampal nitrite levels. Results: Quercetin significantly reduced immobility in the forced swimming test, increased activity in the open-field test, and enhanced grooming behaviour, particularly at 40 mg/kg. Co-administration of an ineffective dose of quercetin (10 mg/kg) with L-NAME increased immobility and grooming activity time. Interestingly, co-administration of the effective dose of quercetin (40 mg/kg) with L-arginine increased immobility time in the FST. Additionally, administration of quercetin at doses of 20 and 40 mg/kg significantly reduced the nitrite level in the hippocampus of SIS mice. Furthermore, co-administration of L-NAME and L-arginine with ineffective and effective doses of quercetin decreased and increased nitrite levels in the hippocampus and increased immobility time in the FST compared to their respective counterparts administered alone. Conclusions: These results suggest quercetin’s potential in alleviating depression by modulating NO levels, pointing to its promise in treating depression associated with chronic stressors like social isolation
A special focus on polyadenylation and alternative polyadenylation in neurodegenerative diseases: A systematic review
Neurodegenerative diseases (NDDs) are one of the prevailing conditions characterized by progressive neuronal loss. Polyadenylation (PA) and alternative polyadenylation (APA) are the two main post-transcriptional events that regulate neuronal gene expression and protein production. This systematic review analyzed the available literature on the role of PA and APA in NDDs, with an emphasis on their contributions to disease development. A comprehensive literature search was performed using the PubMed, Scopus, Cochrane, Google Scholar, Embase, Web of Science, and ProQuest databases. The search strategy was developed based on the framework introduced by Arksey and O'Malley and supplemented by the inclusion and exclusion criteria. The study selection was performed by two independent reviewers. Extraction and data organization were performed in accordance with the predefined variables. Subsequently, quantitative and qualitative analyses were performed. Forty-seven studies were included, related to a variety of NDDs, namely Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Disease induction was performed using different models, including human tissues, animal models, and cultured cells. Most investigations were related to PA, although some were related to APA or both. Amyloid precursor protein (APP), Tau, SNCA, and STMN2 were the major genes identified; most of the altered PA patterns were related to mRNA stability and translation efficiency. This review particularly underscores the key roles of PA and APA in the pathogenesis of NDDs through their mechanisms that contribute to gene expression dysregulation, protein aggregation, and neuronal dysfunction. Insights into these mechanisms may lead to new therapeutic strategies focused on the modulation of PA and APA activities. Further research is required to investigate the translational potential of targeting these pathways for NDD treatment. (Figure presented.)
Association Between Gallstone Disease and Risk of Mortality of Cardiovascular Disease and Cancer: A Systematic Review and Meta-Analysis
BACKGROUND: Gallstone disease (GD) is increasing in the world and has various complications. OBJECTIVE: This study aims to examine the relationship between GD and the risk of mortality from cardiovascular disease (CVD) and cancer using a systematic review and meta-analysis approach. METHODS: A comprehensive and systematic search was done in various databases, such as Web of Science (WOS), Scopus, MEDLINE/PubMed, Cochrane, and Embase. The search included studies published from 1980 to December 2023. Heterogeneity was assessed using Chi-square, I2, and forest plots, while publication bias was evaluated through Begg's and Egger's tests. All analyses were performed using Stata 15, with statistical significance set at p <0.05. RESULTS: A pooled analysis of five studies involving 161,671 participants demonstrated that individuals with GD had a significantly higher risk of mortality from CVD (RR 1.29, 95% CI: 1.11-1.50, p <0.001). Importantly, no evidence of publication bias was found based on the results of Begg's test (p =0.806) and Egger's test (p =0.138). Furthermore, the pooled analysis of seven studies, encompassing a total of 562,625 participants, indicated an increased risk of cancer mortality among individuals with GD (RR 1.45, 95% CI: 1.16-1.82, p <0.001). Similarly, no publication bias was detected through Begg's test (p =0.133) and Egger's test (p =0.089). CONCLUSION: In this study, the evidence of a significant association between GD and an elevated risk of mortality from CVD and canceris provided. These findings suggest that implementing targeted interventions for individuals with gallstone disease could reduce mortality rates among these patients
Evaluation of the COVID-19 vaccine effectiveness on the outcomes of COVID 19 disease in Iran: a test-negative case-control study
Introduction: This study measures the COVID-19 vaccine effectiveness (CVE) against hospital admission and severe COVID-19. Methods: This study is a test-negative case-control design using data from eight provinces in April, 2021 until March, 2022. The individuals were classified as cases and controls based on the results of the RT-PCR test for SARS-CoV-2 and matched based on the timing of the test being conducted as well as the timing of hospital admission. The measure of association was an odds ratio (OR) by univariate and multiple logistic regression. The multiple logistic regression has been carried out to take confounding factors and potential effect modifiers into account. The CVE was computed as CVE = (1 – OR)*100 with 95% confidence interval. Results: Among 19314 admitted patients, of whom 13216 (68.4%) were cases and 6098 (31.6%) were controls, 1313 (6.8%) died. From total, 5959 (30.8%) patients had received the vaccine in which one, two, and booster doses were 2443 (12.6%), 2796 (14.5٪), and 720 (3.7٪), respectively. The estimated adjusted effectiveness of only one dose, two doses and booter vaccination were 22% (95% CI: 14%-29%), 35% (95% CI: 29%-41%) and 33% (95% CI: 16%-47%), respectively. In addition, the adjusted vaccine effectiveness against severe outcome was 33% (95% CI: 19%- 44%), 34% (95% CI: 20%- 45%) and 20% (95% CI: -29%- 50%) for those who received one, two and booster vaccinations, respectively. Conclusion: Our study concluded that full vaccination, though less effective compared to similar studies elsewhere, decreased hospital admissions and deaths from COVID-19 in Iran, particularly during the Delta variant period, with an observed decline during the Omicron variant dominance
The survey of antitumor effects of bromelain on neoplastic breast cells: A systematic review
Background: Breast cancer is one of the most prevalent cancers in women worldwide. Considering the side effects of chemotherapy treatments, we investigated the anticancer effects and mechanisms of bromelain (Br) on breast cancer cells in this systematic review. Methods: The PRISMA recommendations were followed to design this systematic review. Web of Science, PubMed, Cochrane Library, and Scopus were high-coverage databases used for searching. After considering the inclusion and exclusion criteria for the study, 18 articles were included. The desired information was gathered, entered into an Excel file, and the study outcomes were surveyed. Results: Br revealed its anticancer effects by preventing the proliferation of cancer cells, inducing cytotoxicity, apoptosis, autophagy, and cellular oxidation in breast cancer cells. Moreover, its anti-inflammatory activity and immunomodulatory effects in the tumor environment can increase treatment outcomes. No significant side effects of this proteolytic substance have been reported, and it is a safe herbal constitution. Its combination with anticancer drugs such as cisplatin has revealed synergic effects. Besides reducing the toxicity of chemotherapy drugs, Br improves treatment outcomes. Conclusion: Br has shown promising anticancer effects against breast cancer in in vivo and in vitro studies. However, more clinical trial studies are needed to achieve more reliable results