Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent and burdensome neurodegenerative disorder that has been extensively researched to understand its complex etiology, diagnosis, and treatment. The interplay between genetic and environmental factors in PD makes its pathophysiology difficult to comprehend, emphasizing the need for further investigation into genetic and epigenetic markers involved in the disease. Early diagnosis is crucial for optimal management of the disease, and the development of novel diagnostic biomarkers is ongoing. Although many efforts have been made in the field of recognition and interpretation of the mechanisms involved in the pathophysiology of the disease, the current knowledge about PD is just the tip of the iceberg. By scrutinizing genetic and epigenetic patterns underlying PD, new avenues can be opened for dissecting the pathology of the disorder, leading to more precise and efficient diagnostic and therapeutic approaches. This review emphasizes the importance of studying dysregulated cell signaling pathways and molecular processes associated with genes and epigenetic alterations in understanding PD, paving the way for the development of novel therapeutic strategies to combat this devastating disease.

A methodological quality review of citations of randomized controlled trials of diabetes type2 in leading clinical practice guidelines and systematic reviews.

Objective: Evaluate methodological quality of type 2 diabetes RCTs conducted in Iran and cited in clinical practice guidelines and systematic reviews and meta-analyses. Methods: We conducted a descriptive methodological quality review, analyzing 286 Randomized Controlled Trials (RCTs) on diabetes mellitus published in Iran from July 2004 to 2021. We searched six databases systematically and evaluated eligible articles using the CONSORT 2010 checklist for abstracts. Two investigators assessed the data using a 17-item checklist derived from CONSORT. Additionally, we examined the citations of each RCT in 260 clinical practice guidelines, with a specific focus on the adequate reporting of outcomes. Results: Out of 6667 articles, 286 analyzed. Poor reporting and failure to meet criteria observed. Only 3.8% cited in guidelines. Reporting rates: primary outcomes (41.9%), randomization (61.8%), trial recruitment (12.6%), blinding (50.8%). 27.9% cited in systematic reviews, 50.34% in systematic reviews and meta-analyses, 26.57% in meta-analyses. 67.8% of papers cited in systematic reviews. Adherence highest for participants, objective, randomization, intervention, outcome; lowest for recruitment, trial design, funding source, harms, and reporting primary outcomes. Conclusions: Poor methodological reporting and adherence to CONSORT checklist in evaluated RCTs, especially in methodological sections. Improvements needed for reliable and applicable results in guidelines, reviews, and meta-analyses. Inadequate outcome reporting challenges researchers, clinicians, and policymakers, impacting evidence-based decision-making. Urgent improvements in RCT registration necessary.

Dutasteride nanoemulsion preparation to inhibit 5-alpha-hair follicle reductase enzymes in the hair follicle; an ex vivo study.

Alopecia is a treatable disorder that usually occurs due to high levels of 5-alpha dihydrotestosterone in hair follicles. To enhance the storage capacity of hair follicles and alleviate the inherent characteristics of dutasteride, 5-alpha reductase inhibitor, a prolonged-release nanocarrier was synthesised, and its influence on rat abdomen's skin was investigated. Results showed the lower ratio of S/Co (higher ethanol concentration) increased the hydrodynamic nanocarriers' particle size due to thermodynamic disturbance and Ostwald ripening. In contrast, an increase in surfactant through a decrease in interfacial tension resulted in smaller nanocarriers of 32.4 nm. Moreover, an increase in viscosity had an inverse correlation with the nanoemulsions' particle size. Nanocarriers containing ethanol showed less entrapment efficacy, perhaps due to the rapid dissolution of dutasteride into ethanol during nanoemulsification, while, based on Stokes' equation, the addition of ethanol resulted in smaller particle size and stability of the system. Skin permeation analysis using Franz diffusion cells showed nanocarriers could pass through the skin and release dutasteride for 6 days. In conclusion, the optimum concentration of ingredients is decisive in guaranteeing the ideal particle size, stability, and skin permeation of nanocarriers. The Present dutasteride nanocarrier would promise a prolonged and sustained-release drug delivery system for Alopecia therapy.

Pituitary tumor registry: a multidisciplinary program protocol.

Purpose: This registry aims to collect information to create an appropriate platform for the development of a basis for clinical research and basic sciences to carefully study pituitary adenomas. Methods: Demographic data, diagnosis, treatment, and outcome information of the patients with a confirmed diagnosis of pituitary adenomas will be collected by investigators of the registry. Analysis of registry data generates aggregate reports summarizing pituitary tumor epidemiology, treatment, and outcome. These reports include annual public data reports. In the future, the registry program may provide a wider network in Iran and ultimately support the expansion of international studies. Conclusion: For a long time, patients with pituitary adenomas should be observed. Implementing a registration system would greatly reduce the challenges of patients' follow-up so that their monitoring can be improved.

Knowledge gaps in diabetes research: an evidence mapping of the literature.

Background: Mapping the available evidence can be used to inform current diabetes research, identify relevant gaps, and prioritize future research. In this regard, we mapped diabetes research performed in Iran. Method: We searched the Scopus and PubMed databases from 01/01/2015 till 01/01/2020 using keywords such as diabetes and Iran. The included articles were classified according to their document types, level of evidence, and subject areas. Results: The majority of the included articles (53%) were related to diabetes types, followed by complications (28%). Most of the documents were original articles (82%), and reviews were 18% of the publications. Systematic reviews constitute only 6% of the total documents. Observational studies were the most common types of study designs (26%), followed by clinical trials (20%). Moreover, topics on control and management of diabetes were the most prevalent subject areas (58%), and fewer studies were on preventive strategies (6%). In diabetes management studies, less attention has been paid to evaluate psychological (10%), educational (9%), and physical activity-related (7%) interventions. There was a shortage of secondary studies related to physical activity, psychology, diagnostic, and screening-related studies. Conclusion: To fill diabetes research gaps, more investment in cost-effectiveness interventions, such as preventive strategies and behavioral self-management programs, need. Moreover, we need to pay more attention on applied sciences and real world evidence to bridge translational gaps from bench to bedside. In this regard, further data synthesis can be helpful in evaluating the effectiveness of the available studies and avoiding unnecessary investigations.

Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

Objective: Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI. Methods: A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients. Results: Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D. Conclusion: This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes.

Mapping evidence of Iran diabetes research: protocol for a scoping review.

Background: A considerable amount of research funding goes to diabetes management strategies to improve therapeutic goals and reduce the burden of diabetes. A vast amount of the budget is wasted due to unnecessary studies. A scoping review is a pivotal study to overview the available evidence and avoid research waste. In this review, we will try to find out the scope of available studies on diabetes management interventions, identify associated research gaps, and prioritize future studies. Method: We will carry out a study using Arksey and O'Malley's scoping review framework. We will search the Scopus and PubMed databases from 01/01/2015 till 01/01/2020. Only original articles related to pharmacological and non-pharmacological management interventions will be included. These interventional studies should be conducted on the Iranian population. After data extraction, a descriptive data analysis will be used to present information in different charts or tables. We will evaluate related published articles based on their document type, level of evidence, type of diabetes, subject area, interventions types, main findings and outcomes. Discussion: This study represents the first attempt to sum up available studies related to diabetes management interventions performed in Iran. The results of this study will be useful for all the stakeholders and policy-makers involved in diabetes research. It can help clinicians to be informed about studies on management interventions and can guide scientists eager to diabetes research to choose their future research plans based on diabetes research requirements and gaps.