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Suppressor of Cytokine Signaling Proteins 3 and 5 Potentially Delineate Polarization of Th cells in Chronic Rhinosinusitis
No full textBackground: Chronic rhinosinusitis (CRS) is an inflammatory condition classified into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Th cells manage inflammatory cells in CRS. Suppressor of Cytokine Signaling (SOCS) proteins regulate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in Th cells by polarizing toward Th1, Th2, and Th17 cells. This study evaluated the levels of SOCS1,3,5 in CRS patients to find associations with Th cells. Methods: In this cross-sectional study, 20 CRSwNP patients, 12 CRSsNP patients, and 12 controls participated. The infiltration of CD4+ T cells was determined using immunohistochemistry. The expression of specific transcription factors and SOCS proteins was assessed using real-time PCR. Cytokine levels were evaluated using ELISA. SOCS protein levels were investigated using western blot analysis. Results: The expression of SOCS3 increased in the CRSwNP group compared to CRSsNP and control groups (p <0.001). SOCS3 protein levels increased in the CRSwNP group compared to CRSsNP (p <0.05) and control (p <0.001) groups. Although there was a significant difference in SOCS5 expression between CRSsNP and control groups, SOCS5 protein levels were significantly different between CRSsNP and control (p <0.001) and CRSwNP (p <0.05) groups. Conclusions: Targeted therapies may be suggested for CRS by modulating SOCS3 and SOCS5 proteins that are responsible for polarization of Th cells toward Th2 or Th1 cells, respectively. JAK-STAT pathway targeting, which encompasses numerous cells, can be limited to SOCS proteins to more effectively orchestrate Th cell differentiation
The effect of aqueous extract of Iranian oak (Quercus brantii) on antioxidant capacity and oxidative stress in beta-thalassemia patients: Randomized controlled trial
No full textBackground and aim: Frequent administration of blood in β-thalassemia patients can lead to over-loaded iron, a reduction in the levels of antioxidant activities in the body, and oxidative stress. This study was done to evaluate the antioxidant and protective effect of aqueous oak (Quercus brantii) extract supplementation on these patients. Methods: This clinical trial was performed on 60 major β thalassemia patients dividing them into intervention and control groups. In addition to taking desferrioxamine (DFO), the control and intervention groups received respectively placebo capsule supplementation and aqueous Quercus extract capsules (300 mg/day) for 3 months. Serum lipid profiles (LDL-c, HDL-c, triglyceride), Total Antioxidant Capacity (TAC), Glucose, Uric acid, urea nitrogen (BUN), Creatinine, LFT (Liver Function Tests) such as SGOT, SGPT, ALP, Total bilirubin, Direct bilirubin, ferritin, MDA and carbonyl protein (CO) levels were measured before and after the period. In addition, the activity of catalase (CAT), and superoxide dismutase (SOD) was measured in the red blood cell. Furthermore, antioxidant activity and total phenolic content of aqueous Quercus were recorded to standardize capsule formulation. Results: Mean serum MDA, and protein CO, significantly decreased in the intervention group with β-TM after 3 months of treatment with Quercus extract. In addition, the superoxide dismutase (SOD) enzyme and Total antioxidant capacity (TAC) significantly increased in comparison with the control group. Changes in serum creatinine, BUN, and alanine transferase were not significant. In the study, Quercus extract capsules contain 48/56 mg gallic acid/g (dry extract) total phenol, 58/6 mg/g (dry extract), and flavonoids of 63/8 μg/ml antioxidant power which by GC/MS analysis has been measured. At the end of the study, serum MDA decreased from 48.65 ± 8.74 to 43.94 ± 10.39 μ mol/l after administration of oak extract and protein CO dropped from 2.44 ± 0.38 to 1.2 ± 0.31 nmol DNPH/mg protein after administration of the oak extract. At the end of the study serum, TAC increased in patients interventional group from 907 ± 319 to 977 ± 327 μmol FeSO4/l compared to the control group 916 ± 275 to 905.233 ± 233 μmol FeSO4/l with placebo, and SOD increased from 1577 ± 325 to 2079 ± 554 U/l (compared to 1687 ± 323 U/l with placebo). The treatment effect of Quercus was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and SOD, with significant effects being demonstrated for each laboratory parameter (P = 0.15, P = 0.001, P = 0.02, and P < 0.003, respectively). Conclusions: Aqueous Quercus extract, due to its high antioxidant potential, reduced MDA, serum carbonyl protein, and increased superoxide dismutase activity effectively decreased serum OS and enhanced serum antioxidant capacity in patients with β-thalassemia major. oak given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients. Registration information: This study was submitted, evaluated, and approved by the Iranian Registry of Clinical Trials (IRCT: http://www.irct.ir; IRCT2015101411819N4), which was established for national medical schools in Iran
Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
No full textBackground: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation
Effect of mustard analogs on cytokine profile in rodents: A systematic review and meta-analysis
No full textMustard analogs (sulfur and nitrogen forms) are toxic agents that may damage immunity. This meta-analysis investigates the impact of mustard analogs on cytokine profiles in rodent models, emphasizing trends and inconsistencies observed in previous studies. A total of 21 relevant studies that evaluated the effect of mustard analogs on cytokines were screened. Data were extracted, and effect size and heterogeneity were assessed using random-effects models, Cochrane Q, and I2 statistics. The analysis revealed significant elevations in levels of IL1 alpha, IFN-T, IL-1R, IL-6, and TNF alpha and a reduction in the level of IL-10 following mustard exposure. The subgroup analysis showed that sulfur mustard analogs increased IL-1R, IL-6, IFN-gamma, and TNF-alpha levels, while IL-10 levels decreased. Nitrogen mustard analogs also elevated IL-1 alpha, IL-1R, and IL-6. Short-term exposure increased most cytokines, with a decrease in IL-10. In the medium term, all cytokines were elevated except IL-10, which was reduced. Long-term exposure sustained higher levels of IL-1 alpha and IL-6. Analysis of serum, plasma, and BALF samples confirmed significant rises in most cytokines, with IL-10 reduced. Injection routes consistently led to increased cytokines IL-1 alpha, IL-1R, IL-6, IFN-gamma, TNF-alpha and decreased IL-10, whereas vapor and liquid touch routes primarily increased IL-6. It is concluded that mustard analogs induce notable inflammatory responses in rodent models. Among these, sulfur mustard exhibits more extensive systemic effects compared to nitrogen mustard, resulting in more severe inflammation. Additionally, the route of administration substantially influences the severity of the inflammatory response. The exposure length and sample type also affect the cytokine levels, which may mandate the development of targeted treatments to counteract these effects
The Role of Glass Fiber-reinforced Composites in Maxillary Fracture Repair
No full textMaxillary fractures present complex challenges in facial trauma repair due to the intricate anatomy and functional importance of the midface. Traditional fixation methods, such as titanium plates and screws, provide mechanical stability but are associated with complications, including infection, palpability, and interference with imaging. This review examines the role of Glass Fiber-reinforced Composites (GFRC) as an emerging alternative for maxillary fracture repair, emphasizing its mechanical properties, clinical applications, and potential for improving patient outcomes.GFRC offers distinct advantages, including high tensile strength, flexibility, and biocompatibility. These properties enable more effective stress distribution across the fracture site, reducing localized pressure and enhancing bone healing. GFRC's radiolucency and lightweight nature also address aesthetic concerns, as it eliminates the visibility and palpability issues commonly associated with metallic implants. This review compares GFRC to traditional materials such as titanium and composite resorbable polymers, highlighting its superior performance in terms of mechanical stability, patient comfort, and long-term durability. The review also explores emerging technologies in GFRC, such as bioactive coatings and nanotechnology, which have the potential to enhance its biological integration and promote faster bone regeneration
Late presentation of polyserositis following single honey bee sting: A case report
No full textIntroduction and importance: The severity of a bee sting reaction can vary. There are two kinds of responses: local and systemic. The systemic manifestations are rare, especially polyserositis. Polyserositis describes the inflammation of serous membranes such as the pericardium, the pleura, or the peritoneum. We reported a case of polyserositis following a honeybee sting with late presentation. Case presentation: This is a case report of a 30-year-old man who presented with progressive dyspnea, swelling of both lower limbs, and abdominal pain that began three days after the bite. CT showed pericardial, pleural, and abdominal fluid. Echocardiography showed tamponade. He underwent surgery to remove pericardial and pleural fluid. Following surgery, the patient underwent medical treatment. Ten days following treatment he developed a complete resolution of all symptoms and signs. Clinical discussion: Bee stings can be life- threatening. Polyserositis occurring due to honey bee sting is a rare complication. The honey bee sting appeared to cause increased microvascular permeability. Pericardial, pleural effusion, abdominal ascites, and lower limb edema due to honey bee stings are infrequent complications. The physician should know enough about all the possible side effects of bee stings. Conclusion: Physicians should be informed of the rare complications of bee stings. To prevent systemic complications medical treatment is recommended
Adherence to EAT-Lancet reference diet and risk of premature coronary artery diseases: a multi-center case-control study
No full textBackground: In 2019, a globally sustainable dietary pattern that primarily emphasizes the consumption of plant-based foods was proposed by the EAT-Lancet Commission. However, there is limited evidence regarding the association of this diet with coronary events. Objectives: To determine the association between the EAT-Lancet Reference Diet (ELD) and premature coronary artery disease (PCAD) risk and its severity. Methods: This multi-center, case-control study was conducted within the framework of the Iran premature coronary artery disease (I-PAD). A total of 3185 participants aged under 70 years in women and 60 years in men were included. Cases were those whose coronary angiography showed stenosis ≥ 75% in at least one vessel or ≥ 50% in the left main artery (n = 2033), while the controls had normal angiography results (n = 1152). Dietary intake was assessed using a validated food frequency questionnaire. Logistic regression was utilized to examine the association between ELD and presence of PCAD. Results: Compared with individuals in the first quartile, those in the highest quartile of ELD (OR = 0.29, 95% CI: 0.21, 0.39; P for trend < 0.001) and ELD calculated with minimum intake (OR = 0.39, 95% CI: 0.29, 0.52; P < 0.001) had lower risk of PCAD. Individuals in the highest quartile of adherence to the ELD and ELD with minimum intake had 78% and 72% lower risk of having severe PCAD compared with those in the lowest quartile, respectively. Conclusion: An inverse association was observed between adherence to the ELD and PCAD risk and its severity. Large-scale prospective cohort studies are required to confirm these findings
The role of resilience as a key player in mitigating job burnout's impact on workplace safety
No full textIt is probable that resilience can play a significant role in mitigating the impact of job burnout on workplace safety outcomes. Identification of these relations and paths can be useful for reducing burnout effects and reinforcing safety behavior factors. This study seeks to explore the relationship between job burnout and unsafe behavior, with a specific focus on the mediating role of resilience. This cross-sectional study, conducted in 2023, involved 200 workers in the spinning and weaving industries in central Iran. The study used printed questionnaires distributed to study participants during their rest periods to collect data for further analysis. The questionnaires included demographic information, the Maslach burnout inventory, the Connor–Davidson Resilience Scale, and a set of safety behavior questionnaires. Subsequently, the study analyzed various dimensions of job burnout with respect to unsafety behavior by constructing a theoretical model using AMOS software. The results indicate that three burnout dimensions indirectly influence safety compliance through resilience (P < 0.001). Specifically, depersonalization and personal accomplishment directly and indirectly affect safety participation through resilience and safety compliance (P < 0.001). Resilience had the highest direct and total effect coefficients on safety compliance (0.692 and 0.692), while emotional exhaustion exhibited the highest indirect coefficients (− 0.505). Regarding safety participation, the highest direct coefficient was associated with personal accomplishment (0.406), and the greatest indirect and total coefficients with depersonalization (− 0.370 and − 0.588). By recognizing the differential impacts of various burnout dimensions, tailored interventions can be developed to address specific facets of burnout, thus optimizing safety initiatives. Moreover, the pivotal role of resilience unveils a promising avenue for mitigating the adverse effects of burnout on unsafe behaviors
Trihalomethanes in chlorinated drinking water: Seasonal variations and health risk assessment in southern Iran
No full textAssessing the adverse impacts of trihalomethanes, the most hazardous disinfection by-products, is crucial for community health protection. This study evaluated physicochemical parameters, trihalomethane levels, their prediction, and risk assessment using probability and Sobol analysis. Results indicated that electrical conductivity, total dissolved solids, nitrate, sulfate, calcium, lithium, total organic carbon, and ammonium exceeded permissible limits. Tribromomethane (0.14–3.21 μg/L in winter; 0.06–0.17 μg/L in summer), trichloromethane (1.90–3.53 μg/L in winter; 3.19–5.44 μg/L in summer), bromodichloromethane (0.62–4.24 μg/L in winter; 3.27–6.41 μg/L in summer), and dibromochloromethane (0.82–2.41 μg/L in winter; 0.69–3.03 μg/L in summer) remained within safe limits. Random Forest analysis identified total organic carbon as the most significant factor in trihalomethane production, with a positive correlation between trihalomethanes and bromide. Per the World Health Organization's risk assessment, trihalomethane concentrations posed no harm to residents (IWHO<1). However, the United States Environmental Protection Agency's assessment indicated an acceptable low cancer risk (100% cumulative cancer risk for all groups). Additionally, nitrate and fluoride levels surpassed the standard limit, with hazard index above 1 in both seasons for residents. Monte Carlo simulations showed that the 95th percentile of residents faced non-carcinogenic (nitrate and fluoride). However, 100% of children and 99.98% of adults were exposed to an acceptable low carcinogenic risk for THMs. Factors like inhalation rate, body weight, and trihalomethane levels significantly impacted health risk. These findings highlight the necessity for continuous monitoring and effective water treatment to safeguard public health, promote clean water, and advance sustainable development, advocating for sustainable water management to tackle health risks from environmental pollutants like disinfection by-products
Identification of Key Biomarkers and Regulatory Networks in Uterine Cancer Using RNA-Seq Data from TCGA
No full textIntroduction: Uterine cancer (UC) is a leading cause of cancer-related deaths in women globally. The growing incidence of cases emphasizes the need for diagnostic and therapeutic approaches. Conventional diagnostic techniques, such as imaging and biopsy, are frequently expensive, time-consuming, and invasive, restricting their availability and effectiveness. Consequentially, there is an urgent need for more effective, non-invasive, and cost-effective approaches that may be generally adopted for the early detection and appropriate management of UC. This study aimed to identify potential biomarkers for UC diagnosis and elucidate the regulatory networks mediated by miRNAs and transcription factors (TFs) using RNA-Seq data from the Cancer Genome Atlas (TCGA). Methods and Materials: RNA-Seq data for UC and standard tissue samples were obtained from the TCGA using the TCGAbiolinks package in R. The data processing involving normalization and differential expression analysis was performed using the same package. Genes identified as differentially expressed genes (DEGs) were selected based on a p less than 0.05 and a log fold change (LogFC) greater than or equal to 1. The functional importance of DEGs was investigated using gene ontology (GO) and KEGG pathway analyses. Protein-protein interaction networks and hub genes were identified using STRING and Cytoscape. miRNA-target interactions were explored with miRTarBase and miRNet, while TF-target interactions were analyzed using TRANSFAC and ChEA databases. The validation of hub genes was conducted using receiver operating characteristic (ROC) curve analysis and the GEPIA database. Results: According to the analysis, 413 DEGs were identified, with 264 genes upregulated and 149 genes downregulated. The key DEGs identified were CEACAM5, FLNC, CDKN2A, MMP9, KRT5, DCN, CNN1, and SFN. The GO enrichment study revealed essential biological processes, including regulating vascular-associated smooth muscle cell proliferation (GO: 1904705) and the negative regulation of cysteine-type endopeptidase activity involved in the apoptotic process (GO: 0043154). The KEGG pathway analysis revealed significant pathways in cancer development, specifically the p53 signaling pathway and cytokine-cytokine receptor interaction. miRNA interactions highlighted hsa-mir-16-5p, hsa-mir-155-5p, hsa-let-7b-5p, hsa-mir-124-3p, and hsa-mir-941 as key regulators. TF analysis indicated significant interactions with MYC, EGR1, and SUZ12. ROC curve analysis demonstrated the diagnostic potential of the identified hub genes. Conclusion and Discussion: Potential biomarkers for UC include the CEACAM5, FLNC, CDKN2A, MMP9, KRT5, DCN, CNN1, and SFN genes. The identified miRNAs and TFs have significant roles in regulating these genes, providing valuable insights into the molecular pathways that underlie UC. These findings offer promising opportunities to develop innovative diagnostic and therapeutic approaches for UC