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Water seepage flow can dissolve soluble minerals that exist in rock formations. With the development of the excavated area due to dissolution, the water seepage velocity (discharge) into the dissolved rock will also increase. Therefore, water seepage and dissolution propagation are two interrelated processes. Mosul Dam foundation has experienced these processes since its construction, resulting in karstification in the reservoir and foundation of the dam. The present seepage-dissolution measure to minimize this phenomenon relies on traditional cementitious grouts. However, this measure has not been able to address the issue effectively. Currently, there are a few studies on the chemical remediation of soluble rocks under the influence of high-velocity water flow and water pressure. Therefore, the first part of the current study focuses on the impact of high-velocity water flow and water pressure on the dissolution acceleration of gypsum/anhydrite rocks. In the second part, the waterproof capacity of silica colloidal and its impact on the solubility reduction of the rocks is evaluated. Two distinct laboratory models were designed to simulate rock dissolution in the dam abutments and under the dam. Two sets of experiments were conducted on untreated and silica-treated samples. The experiments were executed on the samples extracted from Fatha Formation outcrop and problematic layers of brecciated gypsum situated at varying depths of the Mosul Dam foundation. The obtained findings reveal that the colloidal silica grout markedly prevents the water seepage impact on the soluble rock and that it can be very useful as an alternative to cement-based grouts. [ABSTRACT FROM AUTHOR]

The behaviour of a proposed concrete-face rockfill dam and its face slab during first impounding are examined using three-dimensional finite-element modelling, verified by results of empirical relationships and observed behaviour of similar dams. The study is carried out on the Glevard dam, a 110 m high concrete-face rockfill dam with a crest length of 276 m. Two models are used for the face slab, one with vertical joints and one without. Friction contacts are used between the concrete face and the underlying rockfill, and between adjacent slab pieces, such that relative sliding at these contacts is allowed. Slab deformations and stresses, joint openings and axial forces obtained for the two models are compared. Results indicate that while neglecting face slab joints in the analysis may not significantly influence the calculated total deformations, it can result in substantial underestimation of in-plane horizontal deformations and axial forces, especially near the abutments. In-plane deformations influence the performance of water stops and leakage through slab joints, and axial forces influence slab design. Results also show that using relatively simple geometry and material modelling in a three-dimensional finite-element analysis can yield results in reasonably good agreement with the observed behaviour and the empirical relations obtained from similar dams. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) and gallstones are generally seen together, and many of the risk factors for fatty liver and gallstones are common and similar. Therefore, this study aims to investigate the relationship between NAFLD and gallstones., Methods: This case-control study was conducted in patients referred to Imam Khomeini and Golestan hospitals of Ahvaz University of Medical Sciences in 2023, whose ultrasound showed fatty liver. Patients who were diagnosed with NAFLD by ultrasound were considered as the case group, and patients who did not have diagnostic findings of fatty liver in ultrasound were considered as the control group. Finally, the information recorded in the checklists was statistically analyzed using SPSS version 26 (SPSS Inc.)., Results: Three hundred patients were included in our study, 150 as cases and 150 as controls. There was no significant difference between the groups in terms of gender and age (gender P -value: 0.817/age P-value: 0.102). A statistically significant relationship was found between obesity, diabetes mellitus (DM), the presence of gallstones, and NAFLD (weight p -value < 0.001/DM p -value < 0.001/gallstones P -value: 0.03). In addition, based on binary logistic regression analysis, the presence of gallstones increases the odds of NAFLD by 2.33 times ( P -value: 0.035). Furthermore, having DM and increasing each BMI unit increases the odds of NAFLD by 16 times and 30%, respectively (BMI p -value < 0.001/DM p -value < 0.001)., Conclusion: Based on the results of our study, gallstones are an important risk factor for NAFLD. The possible mechanisms are the existence of common risk factors between gallstones and NAFLD and the reduction of motility and flow of bile in the bile ducts with the presence of gallstones., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Background: In the new era, microbial-based medicine is one of the best strategies that try to modify the normal flora with the aim of treating some disorders. This systematic review and meta-analysis was performed to evaluate the use of probiotics in the treatment of the clinical outcomes in cases with traumatic brain injury.., Methods: In this regard, the search strategy was done using databases such as PubMed, Embase, Scopus, CENTRAL, and Google Scholar, from 2006 until April 2024. All studies about the efficacy of probiotic supplementation on the clinical outcomes in traumatic brain injury patients were retrieved. During the assessment process of the eligible studies, we evaluated clinical characteristics such as the Glasgow Coma Scale score, the Sequential Organ Failure Assessment score, the Acute Physiology and Chronic Health Evaluation II score, referral rate and hospitalization period in the intensive care unit, mortality rate, as well as opportunistic infections in both groups of case and control.., Results: In this study, the authors analyzed data from 6 articles including 391 cases with traumatic brain injury. Our results showed that the probiotic therapy increases the Glasgow Coma Scale score in patients with the average age of more than 50 years. However, there was no a significant difference in the Sequential Organ Failure Assessment and the Acute Physiology and Chronic Health Evaluation scores between the group that had received probiotics and the control group. Although probiotic-based treatment did not significantly affect the intensive care unit admission (or length of stay), but, the risk of infection, and also mortality was significantly lower in the probiotic group (OR: 0.53; 95% CI: 0.3 to 0.8, as well as OR: 0.41; 95% CI: 0.2 to 0.7, respectively).., Conclusions: Overall, due to the modification of microbial flora, probiotic supplements can balance microflora disturbances, which in turn leads to improvement the clinical outcomes in patients with brain injury. Therefore, probiotic-based therapy can be considered as a promising strategy for the treatment of the central nervous system disorders. However, given the limited evidence, more clinical trial studies need to strengthen our results.., (© 2024. The Author(s).)

Purpose: Systemic Lupus Erythematosus (SLE) significantly affects both the quality of life related to health and non-health aspects. This study aims to evaluate the psychometric properties of the Persian version of the Lupus&#95;PRO questionnaire, version 1.7. The questionnaire serves as a specific self-report outcome scale for assessing the treatment outcomes of Lupus disease., Methods: The Lupus&#95;PRO questionnaire, version 1.7, was translated into Persian using the standard forward-backward method. After being completed by 218 patients with Lupus, the psychometric properties of the instrument were examined. The Convergent and Discriminant Validity of the scale were assessed using Average Variance Extracted and Cross Loadings, respectively. The construct validity of the questionnaire was also evaluated through Confirmatory Factor Analysis (CFA). Cronbach's alpha was calculated to assess the reliability of the questionnaire dimensions., Findings: Out of the 218 patients with lupus who participated in the current study, 13 (6%) were male, and 205 (94%) were female. The mean (SD) age of participants was 40.29 (10.94) years. The Average Variance Extracted (AVE) for HRQOL and Non-HRQOL constructs, except for the Coping and Cognition dimension, was greater than 0.50, indicating satisfactory convergent validity. The interdimensional correlation coefficient (Discriminant Validity) for each dimension with other questionnaire dimensions was less than 0.10, indicating that the questionnaire has good convergent and discriminant validity. Additionally, the results of the Confirmatory Factor Analysis (CFA) indicated that the questionnaire was a suitable fit. In terms of reliability, Cronbach's alpha for the various questionnaire dimensions ranged from 0.51 to 0.91, indicating good internal consistency., Conclusion: The Persian version of the Lupus&#95;PRO questionnaire, version 1.7, demonstrates acceptable validity and reliability in the Iranian population. This instrument can effectively measure various aspects of the quality of life in patients with lupus., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Alzheimer's disease (AD) is a devastating kind of dementia that is becoming more common worldwide. Toxic amyloid-beta (Aβ) aggregates are the primary cause of AD onset and development. Superparamagnetic iron oxide nanoparticles (SPIONs) have received a lot of interest in AD therapy over the last decade because of their ability to redirect the Aβ fibrillation process and improve associated brain dysfunction. The potential diagnostic application of SPIONs in AD has dramatically increased this interest. Furthermore, surface-modified engineered SPIONs function as drug carriers to improve the efficacy of current therapies. Various preclinical and clinical studies on the role of SPIONs in AD pathology have produced encouraging results. However, due to their physicochemical properties (e.g., size, surface charge, and particle concentration) in the biological milieu, SPIONs may play the role of a preventive or accelerative agent in AD. Even though SPIONs are potential therapeutic and diagnostic options in AD, significant efforts are still needed to overcome the inconsistencies and safety concerns. This review evaluated the current understanding of how various SPIONs interact with AD models and explored the discrepancies in their efficacy and safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Gliomas account for 75 % of primary malignant CNS tumors. High-grade glioma (CNS WHO grades 3 and 4) have an unfavorable treatment response and poor outcome. CXCR4 is a G protein-coupled receptor that plays an important part in the signaling pathway between cancer cells and tumor microenvironment. CXCR4 overexpression has been shown in a variety of cancers. In this study, we evaluate the potential value of [ 68 Ga]Ga-Pentixafor as a PET/CT CXCR4-probe for in vivo assessment of CXCR4 expression in patients with high-grade glioma and its correlation with tumor grade., Materials and Methods: [ 68 Ga]Ga-CXCR4 PET/CT was performed in the prospective single-center study in treatment-naïve biopsy-proven patients with high-grade glioma. The acquired images were analyzed qualitatively and semi-quantitatively., Result: A total of 26 patients (mean age: 53.3±14.4 years, 11 women, 15 men) were enrolled. CNS WHO grade 3 pathology was seen in 19 % (5/26) of the sample. The patient-based sensitivity of 68 Ga-CXCR4 was 96.2 %. Overall, 28 pathologic lesions were detected, leading to a lesion-based sensitivity of 96.4 %. The median (IQR) SUV max of grade 4 lesions was substantially greater than the grade 3(3.03(2.5-3.7) vs. 1.51(1.2-1.8), p = 0.0145).). The highest tracer activity of organs -beside bladder as the main excretion reservoir-was in lymphoid tissue of Waldeyer's ring (mean SUV max : 7.41), and spleen (mean SUV max : 6.62)., Conclusion: In conclusion, this new application for [ 68 Ga]Ga-Pentixafor PET tracer exhibits excellent visual and semi-quantitative diagnostic properties. Further studies are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Weight regain and insufficient weight loss are major challenges after metabolic bariatric surgery (MBS), affecting patients' comorbidities and quality of life. The current systematic review and meta-analysis aim to assess the efficacy and safety of GLP-1 receptor agonists (GLP-1 RA) in patients with weight regain or insufficient weight loss after MBS., Methods: A systematic search was conducted across PubMed, Embase, Scopus, and Web of Science databases to find the relevant studies., Results: A total of 19 articles were included. The highest doses of liraglutide and semaglutide were 3 mg per day and 1 mg once weekly, respectively, in the included studies. The mean differences in weight and body mass index after treatment were -7.02 kg or 3.07 kg/m 2 , -8.65 or -5.22 kg/m 2 , and -6.99 kg or -3.09 kg/m 2 for treatment durations of ≤ 6 months, 6-12 months, and >12 months with liraglutide, respectively. Additionally, weekly semaglutide showed significantly greater weight loss compared to daily liraglutide, with a mean difference of 4.15 kg. Common complications included nausea (19.1%), constipation (8.6%), abdominal pain (3.7%), and vomiting (2.4%)., Conclusion: Using GLP-1 RA is a safe and effective treatment for weight regain and insufficient weight loss after MBS., (© 2024 World Obesity Federation.)

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

Abstract: We report the case of a 62-year-old man with metastatic castration-resistant prostate cancer with subcutaneous involvement being treated with 177Lu-prostate-specific membrane antigen (PSMA). Before treatment, he was diagnosed with 2 subcutaneous nodules in the chest wall and soft tissue edema in the pubic and inguinal regions showing PSMA avidity. Biopsy and immunohistochemistry assessment confirmed cutaneous metastases from prostate cancer. He received 3 cycles of 177Lu-PSMA, resulting in a decline in PSA levels and resolution of symptoms. This case underscores the challenging diagnosis of cutaneous metastasis from prostate cancer, especially in atypical presentations. We also reviewed all causes of PSMA-avid lesions in the skin and subcutaneous tissues., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Women diagnosed with late-stage ovarian cancer suffer a very high rate of mortality. Accordingly, it is imperative to detect and diagnose the disease as early as possible in its development. Achievement of this aim implies relatively large-scale screening of women at an age of clinical significance through assay of biomarkers for disease present in blood or serum. Biosensor detection offers an attractive technology for the automated detection of such species. Among several biomarkers that have been identified that are present in patients with ovarian cancer, the only one that is commonly tested for in clinical use is cancer antigen 125, which is considered to be a poor biomarker for the disease. Here, we describe several biosensors that developed in the past decade for the detection of ovarian cancer biomarkers such as CA125, human epididymis protein 4 (HE4) and apolipoprotein A1. The challenges presented by the fabrication of biosensor devices for detecting ovarian cancer and the limited number of biosensors developed for this purpose are discussed., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Analytical Science Advances published by Wiley‐VCH GmbH.)

This meta-analysis seeks to investigate the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the recurrence of chronic subdural hematoma (cSDH). Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, this study conducted a comprehensive online search across various databases, including PubMed, EMBASE, CINAHL, Web of Science, and Cochrane, without time restrictions. Two reviewers independently screened titles, abstracts, and full texts based on predetermined criteria, resolving any discrepancies through discussion or consultation with a third reviewer. The quality and risk of bias of the included studies were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Cochrane's tool for evaluating risk of bias in randomized controlled trials. Six studies aligned with the study objectives were included after a systematic search across 6 databases. The RAAS inhibitors group comprised 404 participants, while the control or placebo group included 1828 participants. Analysis for publication bias using the Egger test indicated no bias in the studies (P = 0.151). The odds ratio for cSDH recurrence with RAAS inhibitor use compared to non-use was reported as OR = 1.06; confidence interval 0.6-1.893, p-value = 0.818, showing no significant association between RAAS inhibitor use and cSDH recurrence. The results suggest no significant link between RAAS inhibitor use and cSDH recurrence. However, due to the limited number and design of studies, as well as the lack of clinical trials, further research is needed to determine the effectiveness of this treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multiple sclerosis is an inflammatory demyelinating disease and represents a global health concern. Ocrelizumab, a humanized IgG monoclonal antibody, selectively targets CD20 on B cells and CD20-expressing T cells. This study aimed to compare the efficacy and safety of the biosimilar ocrelizumab candidate (Xacrel) to the originator product (Ocrevus) in Relapsing Multiple Sclerosis (RMS) patients. In this randomized trial, patients received either Xacrel or Ocrevus for 96 weeks. The primary endpoint was the equivalency of the medications in reducing the annualized relapse rate (ARR) at week 48. The secondary endpoints included time to the onset of disability progression confirmed at 12 and 24 weeks, the proportion of relapse-free patients, magnetic resonance imaging (MRI) evaluations, safety assessments, and immunogenicity over 96 weeks. A total of 170 patients were randomized (1:1 ratio). In the per protocol analysis, the upper and lower limits of 95% two-sided confidence intervals of difference between treatments in the 48-week ARR rate were in the predefined margin of - 0.2 to 0.2 (- 0.002; 95% CI - 0.080 to 0.075). The two products were also comparable in terms of other efficacy parameters, safety, and immunogenicity. The results confirmed that Xacrel is equivalent to Ocrevus in terms of 48-week ARR in RMS patients, with no considerable difference in other efficacy parameters and the safety profile during the 96 weeks. The trial was registered in Iranian registry of clinical trials (IRCT) on 10/06/2019 with the registration number of IRCT20150303021315N13 and in Clinicaltrials.gov on 19/07/2021 with the registration code of NCT04966338., (© 2024. The Author(s).)

Objective: To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE)., Design: Observational cohort analysis based on a multicentre international registry., Setting: Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries., Participants: A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins., Methods: Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use., Results: From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76)., Conclusions: In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Breast cancer (BC) is the most prevalent malignancy in females worldwide. Mutations in the DNA repair pathway genes contribute to a significant increase in BC risk. The present study aimed to assess the frequency of polymorphisms in BRCA1, ATM, and CHEK2 genes and their association with BC susceptibility in the Kurdish population from the West of Iran., Methods: In the present case-control study, the distribution of single nucleotide polymorphisms (SNPs) in CHEK2 (rs17879961), ATM (rs28904921), and BRCA1 (rs80357906, rs1555576855, rs1555576858, and rs397509247) genes were investigated in 335 BC cases and 354 healthy-matched controls by Taqman allelic discrimination assay. The chi-square goodness-of-fit test was employed for the assessment of Hardy-Weinberg Equation. Relative risk and odds ratios were calculated based on the Koopman asymptotic score and the Baptista-Pike method, respectively. Also, the sensitivity and specificity of each polymorphism were assessed using the Wilson-Brown test and a P-value < 0.05 indicating significant differences between the two groups in all assessments., Results: Data showed there was a strong association between rs397509247 (OR = 7.53, 95% CI 1.88-90.91, p = 0.004), rs1555576858 (OR = 10.53, 95% CI 0.01-0.51, p = 0.0005), and rs80357906 (OR = 6.33, 95% CI 0.05-0.043, p < 0.0001) in BRCA1 gene and rs17879961 (OR = 3.52, 95% CI 0.084-0.946, p = 0.02) in CHEK2 gene, with BC risk in the population of interest. Among these, rs28904921 in ATM gene demonstrated the strongest association (OR = 72.66, 95% CI 0.007-0.214, p < 0.0001). This suggests that these SNPs, particularly rs28904921, are significantly associated with an increased risk of BC in the studied population., Conclusion: Our results indicated that BRCA1, ATM, and CHEK2 polymorphisms have a high frequency in the Iranian breast cancer population, with some mutant allele frequencies being much higher than those reported in other populations. We have also provided a simple, multiplex, rapid, and accurate genotyping assay that is useful in clinical settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Several previous studies indicated that melatonin supplementation may positively affect glycemic control in patients with diabetes. However, research on the influence of melatonin supplementation on glycemic parameters remains inconclusive. Therefore, this study aimed to assess the impacts of melatonin supplementation on glycemic parameters in type 2 diabetes by conducting a meta-analysis., Methods: PubMed/Medline, Scopus, and Web of Science were comprehensively searched until July 2024 to find eligible randomized clinical trials (RCTs). The overall effect sizes were estimated by using the randomeffect model and presented as weighted mean differences (WMD) with a 95% confidence interval (CI). Furthermore, the heterogeneity among the included trials was assessed by performing the Cochran Q test and interpreted based on the I² statistic., Results: Of the 1361 papers, eight eligible RCTs were included in this meta-analysis. Our findings indicated that melatonin supplementation significantly decreased fasting blood glucose (WMD = -12.65 mg/dl; 95% CI: -20.38, -4.92; P = 0.001), insulin (WMD = -2.30 μU/ml; 95% CI: -3.20, -1.40; P < 0.001), hemoglobin A1c (WMD = -0.79 %; 95% CI: -1.28, -0.29; P = 0.002), and HOMA-IR (WMD, -0.83; 95% CI: -1.59 to - 0.07; P = 0.03)., Conclusion: According to the results of the current meta-analysis, persons with type 2 diabetes who supplement with melatonin had improved glycemic control. It looks that supplementing with melatonin at a dose exceeding 6 mg daily for over a period of 12 weeks may be more successful than other forms of intervention. Nevertheless, further research with larger sample sizes is necessary to draw definitive conclusions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Skin melanoma is a potentially lethal cancer and ranks as the 17th most common cancer worldwide. Overcoming resistance to advanced-stage melanoma is a significant challenge in its treatment. Parthenolide (PAR) is recognized as a potent anticancer small molecule, yet its potential in treating melanoma is poorly investigated., Objective: Our objective was to investigate the apoptotic and anti-metastatic properties of PAR against the A2058 melanoma cells in vitro., Methods: This study employed various assays, such as cytotoxicity, apoptosis, cell cycle analysis, reactive oxygen species (ROS) production, mRNA expressions, western blotting, gelatin zymography, and scratch assay. The synergy between PAR and dacarbazine, a chemotherapy drug for treating skin cancer, was also assessed., Results: Our study revealed that PAR significantly reduced the viability of A2058 cancer cells, demonstrating greater potency against cancer cells compared to normal L929 cells (IC50: 20 μM vs. 27 μM after 24h). PAR increased ROS production, elevated mRNA expression of pro-apoptotic Bax and NME1 genes, and decreased expression of the MITF gene. PAR induced apoptosis and cell cycle arrest in A2058 cells, as evidenced by the increased proportion of cells in the late apoptotic phase and sub-G1 cell cycle arrest. MMP-2 and MMP-9 mRNA and protein expressions, gelatinase activity, and the migration of A2058 cells were also decreased by PAR, suggesting its potential to suppress cancer cell invasion., Conclusion: These results, along with the synergic effect with dacarbazine, indicated that PAR may have the potential to be a therapeutic drug for melanoma by triggering apoptosis and suppressing invasion and migration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Maternal dietary quality may alter the nutrient content of breast milk. In this study, we aimed to investigate the relationship between the healthy eating index (HEI) and alternative healthy eating index (AHEI) of a breastfeeding mother's diet with the antioxidant profile of her breast milk and her infant's urine. This study included 300 healthy mother-infant pairs. The participants' dietary intake was estimated using a validated semi-quantitative food frequency questionnaire. The diet quality of participants was assessed using the HEI and AHEI. The total antioxidant content of the breast milk and infant's urine was evaluated using ferric reducing antioxidant power (FRAP), 2, 2'-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARs), and Thiol quantification assays. After adjusting for confounding factors, the odds of a low malondialdehyde (MDA) content of breast milk were significantly higher in the highest quartile of HEI than in the lowest quartile. The odds of low DPPH and FRAP in infant urine decreased in the highest quartile of HEI compared to the lowest quartile. No significant relationship was found between AHEI and antioxidant levels of breast milk and the infant's urine. Our findings demonstrate that a high quality diet of breastfeeding mothers, identified by a higher HEI, can affect the oxidant-antioxidant balance of a mother's breast milk and her infant's urine., (© 2024. The Author(s).)

Background Cerebrovascular accidents (CVAs), or strokes, are major global health concerns associated with oxidative stress, inflammation, and gastrointestinal complications. This study aimed to explore the impact of postbiotic supplementation in CVA patients, specifically in terms of oxidative stress, inflammation, and clinical outcomes, as an alternative to probiotics with potential advantages. Method A prospective, single-center, randomized, controlled trial was conducted with 120 CVA patients in Iran. These patients were admitted to the ICU to assess the severity of their strokes. Patients were randomly assigned to receive either postbiotic supplementation (n = 60) or a placebo (n = 60). Various biomarkers related to oxidative stress, inflammation, and clinical outcomes were assessed. Data on demographic characteristics, nosocomial infections, and laboratory measurements were collected. Gut microbiota analysis was also performed on fecal samples. Results After the 7-day intervention, postbiotic supplementation resulted in significant improvements in inflammatory markers, oxidative stress, and a reduced incidence of pneumonia compared with those in the control group, with the postbiotic group demonstrating notable decreases in the serum IL-1β levels (-1.79; 95% CI: = -2.9 to -0.64, p = 0.002 ), MDA levels (-30.5; 95% CI: -54.8 to -6.1, p = 0.015), Hs-CRP levels (-0.67; 95% CI:-1.1 to -0.26 mg/dl, p = 0.001) and TAC levels (62.5; 95%CI: 34.1 to 90.9, p < 0.001) compared with those in the placebo group. However, no significant differences in other clinical outcomes, including the NIHSS score, NUTRIC score, and APACHE II score, or the gut microbiota profile, were observed between the two groups. Conclusion Postbiotic supplementation improved the levels of inflammatory factors and oxidative stress markers and reduced the risk of pneumonia in CVA patients. Trial registration This trial is registered in the Iranian Registry of Clinical Trials (registration code IRCT20180712040438N7), Registration date 06122022., (© 2024. The Author(s).)

Background: Nausea and vomiting during pregnancy (NVP) is one of the most common complication of pregnancy. The present study was aimed to determine the association between vomiting during pregnancy and adverse birth outcomes., Methods: A cross-sectional study was conducted on 3649 pregnant women across 11 provinces of Iran. Cluster sampling method was used to select samples and data collection was done using family record and face-to-face interviews. Data were analyzed by logistic regression, using STATA14.2 software., Results: The prevalence of vomiting during pregnancy was 9.7% (95% CI: 8.8, 10.7), with an increasing trend by birth cohort. After adjusting for other confounders, the prevalence of vomiting revealed a decreasing trend by body mass index (OR = 0.63, 95%CI: 0.53, 0.78, P-trend < 0.001). In addition, long inter-pregnancy interval (IPI) significantly increased the odds of NVP (OR IPI of 1-3 year =2.42, OR IPI of >3 year =1.63). Multivariate analyses showed that the odds of stillbirth (AOR = 1.61, 95% CI: 1.17, 2.19) and the odds of infant mortality (AOR = 1.78, 95% CI: 1.29, 2.45) were significantly increased in women with daily vomiting during pregnancy. The odds of vomiting during pregnancy was significantly shown to reduce the odds of abortion by 45%., Conclusion: The prevalence of NVP was shown to have an increasing trend in Iran. This complication is associated with many adverse health outcomes during pregnancy and negatively affect maternal and fetal health. Given the importance of pregnancy period, nutrition education and increase the awareness of pregnant women towards NVP, especially pre-pregnancy training is suggested., (© 2024. The Author(s).)

Background: Considering the vasopressor drug categories and doses that can be used for elderly patients following hypotension are few, the present trial aimed to compare the effect of different doses of phenylephrine infusion on the prevention of hypotension in elderly patients undergoing orthopaedic lower extremities surgery., Methods: This randomised, double-blind prospective clinical trial was conducted by including 60 elderly patients older than 60 years and classified as American Society of Anesthesiology class I and II who were candidates for femur fracture fixation surgery. White and black cards randomly allocated patients to: group A (25µg/kg/h phenylephrine) or group B (35µg/kg/h phenylephrine)., Results: At the T 3 -T 7 time points, group A's systolic and diastolic blood pressure was significantly higher than in group B's (p < 0.05). However, after 27 minutes (T 0 -T 7 ) of phenylephrine infusion, statistical analysis showed no significant difference between the two groups regarding blood pressure (T 8 -T end ). The frequency of bradycardia and reactive hypertension in group B were significantly higher than in group A (p = 0.02) and (p = 0.03), respectively. There was no significant difference between the bleeding loss, blood transfusion and crystalloid volume in both groups (p > 0.05)., Conclusion: Our trial illustrated that high-dose phenylephrine infusion could not assure haemodynamic stability and may cause some side effects., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Heart valve replacement (HVR) surgery represents a significant life event that can potentially impact the well-being (WB) of patients; however, there is a shortage of research on the understanding of WB in HVR patients. This study aims to elucidate the WB experiences of patients who have undergone HVR surgery., Methods: A qualitative directed content analysis approach was employed, focusing on patients who had undergone HVR surgery at hospitals affiliated with Mashhad University of Medical Sciences in Iran from March 2021 to June 2022. Data collection involved conducting 23 face-to-face, semi-structured, in-depth interviews with HVR patients until data saturation was reached. Data analysis was performed using the Elo and Kyngäs approach in MAXQDA software version 10., Results: The analysis revealed 11 generic categories based on the Biopsychosocial-Spiritual (BPSS) model, encompassing the WB experiences of HVR patients. These categories included physical improvements, facilitated treatment compliance, personal and environmental mastery, optimism in life, resilience, healing therapeutic communication of medical staff, a positive supportive atmosphere, job and financial assurance, faith in a higher power, optimism regarding a purposeful future, and gratitude mixed with generosity., Conclusion: The findings of the current study revealed that the experience of WB in HVR patients was influenced by various conditions. By recognizing these conditions, healthcare providers can develop targeted interventions to improve the WB experience in these patients. Also, the findings provide a foundation for future research on WB in medical contexts., Competing Interests: None declared., (Copyright: © International Journal of Community Based Nursing and Midwifery.)

Introduction: Neonatal diabetes mellitus (NDM) is a rare non-immunological monogenic disorder characterized by hyperglycemic conditions primarily occurring within the first 6 months of life. The majority of cases are attributed to pathogenic variants in genes affecting beta-cell survival, insulin regulation, and secretion. This study aims to investigate the genetic landscape of NDM in Iran., Methods: We recruited a total of 135 patients who were initially diagnosed with diabetes at <12 months of age in Iran and referred to pediatric endocrinology clinics across the country. These patients underwent genetic diagnostic tests conducted by the Exeter Molecular Genetics Laboratory in the UK. The pathogenic variants identified were sorted and described based on type, pathogenicity (according to ACMG/AMP criteria), novelty, and the affected protein domain., Results: Genetic defects were identified in 93 probands, presenting various pathogenic abnormalities associated with NDM and its associated syndromes. 76% of the patients were born as a result of consanguineous marriage, and a familial history of diabetes was found in 43% of the cases. A total of 58 distinct variants in 14 different genes were discovered, including 20 variants reported for the first time. Causative variants were most frequently identified in EIF2AK3, KCNJ11, and ABCC8, respectively. Notably, EIF2AK3 and ABCC8 exhibited the highest number of novel variants., Discussion: These findings provide valuable insights into the genetic landscape of NDM in the Iranian population and contribute to the knowledge of novel pathogenic variants within known causative genes., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Different categories of extracellular vesicles (EVs) are identified based on their origin and formation processes. Among these, exosomes (EXOs) originate from endosomal compartments merging with the plasma membrane, forming small lipid vesicles that transport a range of molecular cargo such as nucleic acids, proteins, and lipids. The composition of EXOs varies depending on their cellular source, encompassing various cell types, including neutrophils, dendritic cells, and even tumor cells. Remarkably, EXOs possess inherent stability, low immunogenicity, and compatibility, making them efficient nano vectors for drug delivery. Imaging techniques like bioluminescence, fluorescence, and nuclear imaging are crucial in non-invasively tracking EXOs within living organisms. This process requires the attachment of radionuclides to the EXO's structure without altering its essential characteristics. Real-time imaging of EXOs is vital for their clinical application, and recent advancements in labeling and tracking methodologies provide insights into biodistribution, functionality, and potential pathways for EXO-mediated drug delivery. This review presents updated progress in the diverse applications of EXOs in targeted imaging across various modalities, where they function as contrast agents facilitating tissue visualization and disease tracking. Consequently, EXOs emerge as promising entities in medical diagnostics and imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Metabolic risk factors significantly elevate the risk of cardiovascular diseases (CVDs) and are recognized as one of the primary contributors to these conditions. This study explored the trends and percentage changes in disability-adjusted life years (DALYs) attributable to metabolic risk factors for CVD from 1990 to 2019. Methods: Data from the Global Burden of Disease study was utilized to depict changes across metabolic risk factors by sociodemographic indices and sex groups. The Mann-Kendall test was employed to ascertain the significance of these trends. Results: The findings indicate that the DALY percentage change over these years was more pronounced in low-middle and middle Socio-demographic Index (SDI) countries than in others. The most substantial percentage increase, approximately 60%, was observed in regions with low SDI, attributed to high body mass index (BMI). On average, the greatest DALYs were associated with high systolic blood pressure (SBP). Moreover, the trend for high low-density lipoprotein cholesterol and high SBP declined in countries with high SDI. Conclusions: It can be concluded that to mitigate the global mortality and morbidity from heart diseases, there needs to be a focused emphasis on managing metabolic risk factors, particularly in low-Middle and middle SDI countries.

Background: Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties., Objective: This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients., Methods: This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester., Results: The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalase before silymarin  = 9.29 ± 7.02 vs Catalase after silymarin  = 5.32 ± 2.97, p  = 0.007 and MDA before silymarin  = 4.29 ± 1.90 vs MDA after silymarin  = 1.66 ± 0.84, p  < 0.001) while MMSE increased notably (MMSE before silymarin  = 10.39 ± 6.42 vs MMSE after silymarin  = 13.37 ± 6.81, p  < 0.001)., Conclusion: Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD.

Carbon monoxide (CO) is produced via incomplete combustion of fossil fuels and it may cause long-term neurological sequel upon exposure. Hesperidin (HES), a flavanone glycoside found in citrus plants, exerts diverse beneficial health effects. The present study mechanistically examined the neuroprotective effects of HES in CO-poisoned rats. Thirty male Wistar rats (five groups of six animals) were exposed to 3000 ppm CO for 1 h. Immediately after the exposure and on the next 4 consecutive days (totally five doses), rats intraperitoneally received either normal saline (the control group) or different doses of HES (25, 50, and 100 mg/kg). A sham group that was not exposed to CO was also considered. After evaluation of spatial learning and memory using a Morris water maze (MWM), animals were sacrificed and oxidative stress status in blood samples, and Akt, Bax, Bcl2, and brain-derived neurotrophic factor (BDNF) expression in brain samples were assessed. Western blot analysis indicated increased Akt but decreased Bax/Bcl2 levels in the HES 100 mg/kg, and induced BDNF levels in all HES-treated groups. MWM results showed that HES significantly decreased memory loss. The current findings indicate that HES could alleviate neurological impairments induced by CO in rats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Necrotizing enterocolitis (NEC) is a multifactorial disease primarily affecting infants with very low birth weight (VLBW). Research has shown that the pathogenesis of NEC is associated with abnormal bacterial colonization. Synbiotics, dietary supplements containing probiotics (beneficial bacteria) and prebiotics (non-digestible food), can alter the gut microbiome., Methods: A double-blind, randomized controlled trial was conducted to assess the efficacy of PediLact®, an oral drop multi-strain synbiotic containing Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium infantis, on nutritional parameters and the occurrence of NEC in VLBW neonates. In this study, 118 VLBW neonates from neonatal intensive care units were randomly allocated in a 1:1 ratio to receive either a synbiotic or a placebo. The synbiotic administration continued until the infant was fully fed. The primary outcomes were the occurrence of NEC and the number of days required to achieve full enteral feeding. Log-binomial regression and ANOVA/ANCOVA models were used for analysis., Results: In the group that received the synbiotic, the incidence of NEC decreased significantly (adjusted RR = 0.22, 95% CI: 0.07-0.72, P value = .01; adjusted RD = -0.22, 95% CI: -0.33 to -0.12, P value < .001; NNT = 5). Additionally, feeding intolerance was less frequent in this group (adjusted RR = 0.27, 95% CI: 0.14-0.51, P value < .001; NNT = 3). Furthermore, consumption of the synbiotic was associated with significant weight gain (approximately 40 g) in infants (adjusted SMD = 0.63; 95% CI: 0.26-1.00, P value < .001). The duration of hospitalization and the time required to reach full enteral feeding were also significantly shorter in the synbiotic group (by approximately 3 days). No serious side effects were reported., Conclusion: Prescribing multi-strain synbiotics reduces the incidence of NEC in VLBW infants and has beneficial effects on breastfeeding tolerance and weight gain velocity. Therefore, physicians may consider prescribing synbiotics to VLBW neonates., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)