Repository of Research and Investigative Information Isfahan University of Medical Sciences
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Marital status and risk of type 2 diabetes among middle-aged and elderly population: a systematic review and meta-analysis
No full textBackground: Marital status is among the factors influencing type 2 diabetes mellitus (T2DM). However, the precise relationship remains incompletely understood. This meta-analysis aims to evaluate the association between marital status and the incidence of T2DM. Methods: A review and meta-analysis of observational studies were conducted to investigate the relationship between marital status and diabetes incidence. We searched three databases, including PubMed, Google Scholar, and Scopus, for relevant studies published up to August 16th, 2023. In our initial search, we identified a total of 358 articles. After a demanding screening process involving evaluating titles, abstracts, and full-text content, we ultimately included six studies for our meta-analysis. Result: Comprising a total of 1,440,904 participants, our study found that in comparison to married individuals, unmarried participants exhibited a higher likelihood of developing diabetes odds ratio (OR): 1.47, 95% confidence interval (CI): 0.88-2.45, I-2: 91%, p-value = 0.14. Divorced participants had a reduced likelihood of developing diabetes compared to married participants (OR: 0.84, 95% CI: 0.77-0.91, I-2: 17%, p < 0.001). Similarly, widowed participants showed a lower risk of developing diabetes compared to divorced participants (OR: 0.35, 95% CI: 0.26-0.46, I-2: 83%, p < 0.00001). Conclusion: This study provides strong evidence of links between marital status and type 2 diabetes risk. Unmarried individuals are more susceptible to T2DM, divorced individuals have a lower risk, and widowed individuals exhibit reduced T2DM risk. Further research should investigate underlying mechanisms and confounding factors
Genetic advancements in breast cancer treatment: a review
No full textBreast cancer (BC) remains a leading cause of cancer-related deaths among women globally, highlighting the urgent need for more effective and targeted therapies. Traditional treatments, including surgery, chemotherapy, and radiation, face limitations such as drug resistance, metastasis, and severe side effects. Recent advancements in gene therapy, particularly CRISPR/Cas9 technology and Oncolytic Virotherapy (OVT), are transforming the BC treatment landscape. CRISPR/Cas9 enables precise gene editing to correct mutations in oncogenes like HER2 and MYC, directly addressing tumor growth and immune evasion. Simultaneously, OVT leverages genetically engineered viruses to selectively destroy cancer cells and stimulate robust antitumor immune responses. Despite their potential, gene therapies face challenges, including off-target effects, delivery issues, and ethical concerns. Innovations in delivery systems, combination strategies, and integrating gene therapy with existing treatments offer promising solutions to overcome these barriers. Personalized medicine, guided by genomic profiling, further enhances treatment precision by identifying patient-specific mutations, such as BRCA1 and BRCA2, allowing for more tailored and effective interventions. As research progresses, the constructive interaction between gene therapy, immunotherapy, and traditional approaches is paving the way for groundbreaking advancements in BC care. Continued collaboration between researchers and clinicians is essential to translate these innovations into clinical practice, ultimately improving BC patients' survival rates and quality of life
Nutritional Interventions in Amyotrophic Lateral Sclerosis: From Ketogenic Diet and Neuroprotective Nutrients to the Microbiota-Gut-Brain Axis Regulation
No full textAmyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with significant challenges in diagnosis and treatment. Recent research has highlighted the complex nature of ALS, encompassing behavioral impairments in addition to its neurological manifestations. While several medications have been approved to slow disease progression, ongoing research is focused on identifying new therapeutic targets. The current review focuses on emerging therapeutic strategies and personalized approaches aimed at improving patient outcomes. Recent advancements highlight the importance of targeting additional pathways such as mitochondrial dysfunction and neuroinflammation to develop more effective treatments. Personalized medicine, including genetic testing and biomarkers, is proving valuable in stratifying patients and tailoring treatment options. Complementary therapies, such as nutritional interventions like the ketogenic diet and microbiome modulation, also show promise. This review emphasizes the need for a multidisciplinary approach that integrates early diagnosis, targeted treatments, and supportive care to address the multisystemic nature of ALS and improve the quality of life for patients
The Role of ΔFosB in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies
No full textLevodopa-induced dyskinesia (LID) represents a significant complication associated with the long-term administration of levodopa (L-DOPA) for the treatment of Parkinson's disease (PD). This review examines the critical role of Delta FosB, a transcription factor, in the pathogenesis of LID and explores potential therapeutic interventions. Delta FosB accumulates within the striatum in response to chronic dopaminergic stimulation, thereby driving maladaptive changes that culminate in dyskinesia. Its persistent expression modifies gene transcription, influencing neuronal plasticity and contributing to the sustained presence of dyskinetic movements. This study explains how Delta FosB functions at the molecular level, focusing on its connections with dopamine D1 receptors, the cAMP/PKA signaling pathway, and its regulatory effects on downstream targets such as DARPP-32 and GluA1 AMPA receptor subunits. Additionally, it examines how neuronal nitric oxide synthase (nNOS) affects Delta FosB levels and the development of LID. This review also considers the interactions between Delta FosB and other signaling pathways, such as ERK and mTOR, in the context of LID and striatal plasticity. Emerging therapeutic strategies targeting Delta FosB and its associated pathways include pharmacological interventions like ranitidine, 5-hydroxytryptophan, and carnosic acid. Furthermore, this study addresses the role of JunD, another component of the AP-1 transcription factor complex, in the pathogenesis of LID. Understanding the molecular mechanisms by which Delta FosB contributes to LID offers promising avenues for developing novel treatments that could mitigate dyskinesia and improve the quality of life for PD patients undergoing long-term L-DOPA therapy
Safety and effectiveness of a biosimilar somatropin (Cinnatropin®) in children and adolescents receiving growth hormone therapy over 1 year: a registry-based phase IV study
No full textGrowth hormone therapy has been shown to be effective in treating a variety of growth-related disorders. This post-marketing study assessed the effectiveness and safety of Cinnatropin (R), a biosimilar growth hormone product. The data from the Orchid-Life Registry, which collects long-term effectiveness and safety data from patients receiving Cinnatropin (R), was analyzed. A total of 20,465 patients were enrolled in this study, including 405 subjects in the longitudinal analysis. The most common diagnosis was growth hormone deficiency. The mean (SD) height standard deviation score (HSDS) increased from - 1.71 (1.31) to - 1.32 (1.26) in the cross-sectional population and from - 1.84 (1.18) to - 1.49 (1.13) in the longitudinal population over a period of 12 months. The baseline age exhibited an inverse correlation with changes in HSDS, suggesting that older individuals had smaller increments. Over 80 of prepubertal patients reached targeted height velocity after 1 year of treatment. The majority of adverse events were categorized as non-serious, designated as grade one in severity (mild). The most frequently observed adverse events were injection site reaction and headache.Conclusion: The study indicates that Cinnatropin (R) treatment results in height improvement over 1 year with an acceptable safety profile
A non-fluorescent immunohistochemistry method for measuring autophagy flux using MAP1LC3/LC3 and SQSTM1 as core markers
No full textMacroautophagy/autophagy is a crucial cellular process for degrading and recycling damaged proteins and organelles, playing a significant role in diseases such as cancer and neurodegeneration. Evaluating autophagy flux, which tracks autophagosome formation, maturation, and degradation, is essential for understanding disease mechanisms. Current fluorescence-based methods are resource-intensive, requiring advanced equipment and expertise, limiting their use in clinical laboratories. Here, we introduce a non-fluorescent immunohistochemistry (IHC) method using MAP1LC3/LC3 and SQSTM1 as core markers for autophagy flux assessment. LC3 levels reflect autophagosome formation, whereas SQSTM1 degradation and a decrease in the number of its puncta indicate active flux (i.e., lysosomal turnover). We optimized chromogenic detection using diaminobenzidine (DAB) staining and developed a scoring system based on puncta number and the percentage of stained cells. This accessible, cost-effective method enables reliable autophagy quantification using a standard light microscope, bridging the gap between experimental research and clinical diagnostics. Our protocol allows accurate autophagy evaluation in fixed tissues, offering practical applications in biomedical research and clinical pathology assessment
The effect of low-carbohydrate diets, based on changes in intake of dietary saturated fats on circulating TNF-alpha and interleukin- 6 levels in adults: a systematic review and meta-analysis of randomized controlled trials
No full textBACKGROUND: Low-carbohydrate diets (LCDs) have been associated with inflammation while there is still conflicting evidence regarding the effects of this type of diet on inflammatory markers and the clinical benefit of them remains uncertain. So, we aimed to ascertain the effects of LCDs on serum concentrations of tumor necrosis factor alpha (TNF-alpha) and interleukin- 6 (IL- 6) by performing a systematic review and meta-analysis of randomized clinical trials (RCTs). METHODS: The online databases PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Scopus were comprehensively searched up to February 2024, to find pertinent RCTs. Pooled weighted mean difference (WMD) with 95 confidence intervals (CIs) were calculated using the random-effects model. RESULTS: This meta-analysis of 33 studies assessed a total of 2106 adults irrespective of their health status. Compared with control group, participants on LCDs experienced a decline in IL- 6 levels (WMD: - 0.31 pg/mL; 95 CI: - 0.49 to - 0.12; P = 0.001). However, no significant effect was revealed for TNF-alpha (WMD: - 0.02 pg/mL; 95 CI: - 0.08 to - 0.03; P = 0.449). Stratification analyses indicated that beneficial effects of LCDs on inflammatory cytokines (WMD: - 0.28 pg/mL; 95 CI: - 0.47 to - 0.10; P = 0.003, WMD: - 0.26 pg/mL; 95 CI: - 0.48 to - 0.03; P = 0.027, for TNF-alpha and IL- 6, respectively) were stronger when carbohydrate intake was < 10. The results of Meta-regression analyses suggested that baseline level of both markers remained as a strong predictor of the effect size (P = 0.038 and P = 0.001 for TNF-alpha and IL- 6, respectively). CONCLUSION: Adherence to LCDs appeared to be effective at improving inflammatory cytokines particularly, when carbohydrate intake was restricted to less than 10 of total energy. Nevertheless, further rigorously designed clinical trials considering factors such as race and genetic, the sources and quality of dietary carbohydrates, protein, and fat are required to gain a deeper understanding of the impact of LCDs on inflammatory markers. TRIAL REGISTRATION: PROSPERO, registration no: CRD42023387452
Progression independent of relapse activity and relapse-associated worsening in seronegative NMOSD: an international cohort study
No full textBACKGROUND: Previous studies have indicated that progression independent of relapse activity (PIRA) is uncommon in patients with aquaporin- 4 antibody-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD). However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD. METHODS: We conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data. RESULTS: This study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1), whilst RAW was documented in 7 cases (7.5). CONCLUSION: This international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses
Gynecologic health of women with multiple sclerosis: An overview on the current status and findings of Pap tests in a low-income setting
No full textBACKGROUND: Women with MS (wwMS), particularly ones in low-income settings, and exposed to disease-modifying therapy (DMT), could have specific gynecological health-related issues. AIM: To assist policy making and lead further research by describing the current status of gynecological health and Pap test results in wwMS. METHODS: Cross-sectional study on wwMS living in Isfahan, Iran. Participants were surveyed and referred for a Pap test, results of which were compared with 1:2 age- and socioeconomic status-matched healthy controls (HC). Primary outcome was the degree of non-benign squamous/glandular cell abnormalities. Secondary outcomes were presence of evidence of infection, and the degree of benign inflammatory/reactive changes. Logistic regression models were utilized for analyses. RESULTS: 197 wwMS were included (mean age SD, 41.2 8.3; median EDSS (IQR) 1.5 0.5). 74.1% reported having sexual activity more than once per week in the past year. For contraception, 21.6% and 16.8% used calendar-based methods and male condoms, respectively. 7% had contracted a gynecological infection in the past. Only 1% had received HPV vaccination. Compared to HC, benign reactive/inflammatory changes in Pap tests were less frequently seen in the wwMS (OR: 0.3; 95% CI: 0.2, 0.4; p < 0.001), while evidence of infection was seen more frequently (OR: 11.5, 95% CI: 3.3, 40; p < 0.001). Results were consistent across DMT groups except anti-CD20 therapies. Additionally, the frequency of non-benign changes in wwMS was two times of that in the HC, but the study lacked adequate power to confirm statistical significance (1.5% vs. 0.8%, OR: 2; 95% CI: 0.4, 10.1; p = 0.39). CONCLUSION: There is room for improvement of the gynecological health status of wwMS who live in low-income settings. Also, findings support an immune dysfunction in the cervices of DMT-exposed wwMS. Additionally, further research is merited to determine the risk of changes of malignant potential in cervices of wwMS
Language and Memory Network Alterations in Temporal Lobe Epilepsy: A Functional and Structural Connectivity Study
No full textBACKGROUND AND PURPOSE: This study evaluated preoperative alterations and postoperative reorganization of the joint language-memory network (LMN) from the perspective of resting-state functional and structural connectivity in Temporal lobe epilepsy (TLE). Graph theory and machine learning approaches were employed to explore automatic lateralization. MATERIALS AND METHODS: Resting-state fMRI and DTI data were obtained from 20 healthy subjects and 35 patients with TLE. Functional and structural connectivity were calculated within the LMN before and after temporal lobectomy. ANOVA was performed to identify significant connectivity differences between groups. Four local graph measures were extracted from functional and structural connectivity matrices. Standard feature selection techniques and genetic algorithm (GA) methods were applied to select the optimal features. Subsequently, the K-nearest neighbor, support vector machine (SVM), Naive Bayes, and logistic regression classification methods were used to classify healthy controls (HCs) and pre-surgical TLE groups, as well as pre-surgical left TLE (LTLE) and right TLE (RTLE) groups. Also, relationships between psychological scores and the selected features were evaluated using a linear regression method. RESULTS: The results demonstrated increased functional and decreased structural connectivity in TLE patients before surgery. After surgery, significant connections revealed reduced functional connectivity and increased structural connectivity in TLE patients. Functional analysis identified the left parahippocampal region in LTLE and the right temporal regions in RTLE as key areas. Structural connectivity analysis showed that memory-related areas in the bilateral occipital region and the left language-related area were the origins of alterations. The GA method achieved the highest classification performance using SVM for fMRI and DTI graph measures, with accuracy rates of 97 and 88 for distinguishing LTLE from RTLE, and 93 and 87 for distinguishing TLE from HC, respectively. Moreover, a significant relationship was observed between the best-selected features and memory-assisted cognitive tests. CONCLUSIONS: Pre-surgical functional hyperconnectivity and post-surgical hypoconnectivity and also newly observed bilateral postsurgical structural connectivity, highlighting functional and structural alterations in the LMN network. Additionally, the study underscores the potential of machine learning for TLE diagnosis and lateralization. A limited sample size, particularly in the postsurgical group was one of the constraints of this study. ABBREVIATIONS: TLE=Temporal lobe epilepsy; LMN=Language-memory network; GA=Genetic algorithm; HC=Healthy controls; LTLE=Left TLE; RTLE=Right TLE; AUC=Area under the curve