Novel blood and tissue-based mitochondrial D-loop mutations detected in an Iranian NAFLD patient cohort.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease characterized by an elusive etiology. In its advanced stages, this condition can pose life-threatening implications. Mitochondrial dysfunction due to its impact on hepatic lipid homeostasis, cytokine release, ROS production, and cell death, contributes to the pathogenesis of NAFLD. Previous research reveals a direct link between NAFLD genetic predictors and mitochondrial dysfunction. The emphasis on the D-loop stems from its association with impaired mtDNA replication, underscoring its crucial role in NAFLD progression. We included 38 Iranian NAFLD patients (comprising 16 patients with non-alcoholic fatty liver [NAFL] and 22 patients with non-alcoholic steatohepatitis [NASH]), with matched blood and liver tissue samples collected from each to compare variations in the mitochondrial D-loop sequence within samples. The mitochondrial DNA (mtDNA) D-loop region was amplified using PCR, and variations were identified through sequencing. The resultant sequences were compared with the reference sequence of human mtDNA available in the MITOMAP Database for comparative analysis. In this study, 97 somatic mutations in the mtDNA D-loop region were identified in NAFLD patients. Our study revealed significant difference between the NAFLD patients and control group in 13 detected mutations (P ≤ 0.05). Novel mutations were discovered in hepatic tissues, while mutation 16220-16221ins C was found in both tissues and blood. A significant difference was found in the distribution of D310 and mt514-mt523 (CA)n repeat variations between NAFLD patients and the control group (P < 0.001). C to T and T to C transitions were the prevalent substitution among patients. Identification of the 16220-16221ins C mutation in both blood and tissue samples from NAFLD patients holds substantial promise as a potential diagnostic marker. However, further research is imperative to corroborate these findings.

JAK Inhibitors in Cutaneous T-Cell Lymphoma: Friend or Foe? A Systematic Review of the Published Literature.

Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation (allo-SCT). CTCL is significantly influenced by disruption of JAK/STAT signaling. Therefore, Janus kinase (JAK) inhibitors may be promising for CTCL treatment. This study is a systematic review aiming to investigate the role of JAK inhibitors in the treatment of CTCL, including their efficacy and safety. Out of 438 initially searched articles, we present 13 eligible ones. The overall response rate (ORR) in the treatment with JAK inhibitors in clinical trials was 11-35%, although different subtypes of CTCL showed different ORRs. Mycosis fungoides showed an ORR of 14-45%, while subcutaneous-panniculitis-like T-cell lymphoma (SPTCL) displayed an ORR ranging from 75% to 100%. Five cases were reported having a relapse/incident of CTCL after using JAK inhibitors; of these, three cases were de novo CTCLs in patients under treatment with a JAK inhibitor due to refractory arthritis, and two cases were relapsed disease after graft-versus-host disease treatment following allo-SCT. In conclusion, using JAK inhibitors for CTCL treatment seems promising with acceptable side effects, especially in patients with SPTCL. Some biomarkers, like pS6, showed an association with better responses. Caution should be taken when treating patients with an underlying autoimmune disease and prior immunosuppression.

The battle against colistin-resistant E. coli and the need for a one health approach.

Promoting the judicious use of antibiotics is crucial. Physicians and veterinarians must adhere to evidence-based guidelines and prescribe antibiotics only when necessary [26]. Improved diagnostic tools can help identify the most appropriate treatment options.

Prevalence of Compartment Syndrome and Disseminated Intravascular Coagulation following Rhabdomyolysis; a Systematic Review and Meta-Analysis.

Abstract. Introduction: Rhabdomyolysis (RM) may cause some complications such as compartment syndrome and disseminated intravascular coagulation (DIC), which can affect its prognosis. This systematic review and meta-analysis aimed to investigate the prevalence of the mentioned complications following RM. Methods: Medline, Embase, and Scopus databases were searched using keywords related to compartment syndrome, DIC, and rhabdomyolysis with appropriate combination. Cohort and cross-sectional studies that conducted research on the prevalence of compartment syndrome and DIC in patients with RM were included in the present study. The desired data were extracted from the included studies and meta-analysis was conducted on them to calculate pooled prevalence of these complications. Results: Twenty articles were included in our systematic review. The rate of compartment syndrome reported in these studies ranged from 0 to 30.7%. Our meta-analysis revealed the pooled prevalence of 4% (95% confidence interval (CI): 2.20 to 7.40) for compartment syndrome in these studies. The pooled prevalence of this complication was 7.1% (95% CI: 2.90 to 16.00) among patients with severe RM and 4.4% (95% CI: 1.80 to 10.00) in traumatic RM. The rate of DIC reported in the included studies ranged from 0 to 40.47%. Our meta-analysis showed the pooled prevalence of 8.3% (95% CI: 03.90 to 16.50) for this complication among RM patients. Conclusion: We reported the rates of compartment syndrome and DIC in RM patients based on rhabdomyolysis etiologies through an epidemiologic systematic review and meta-analysis. The rate of compartment syndrome was slightly higher in patients with severe RM and its rate in patients with traumatic RM was close to the overall rate of compartment syndrome.

Investigation of FGF21 mRNA levels and relative mitochondrial DNA copy number levels and their relation in nonalcoholic fatty liver disease: a case-control study.

Background: Although the exact mechanisms of nonalcoholic fatty liver disease (NAFLD) are not fully understood, numerous pieces of evidence show that the variations in mitochondrial DNA (mtDNA) level and hepatic Fibroblast growth factor 21 (FGF21) expression may be related to NAFLD susceptibility. Objectives: The main objective of this study was to determine relative levels of mtDNA copy number and hepatic FGF21 expression in a cohort of Iranian NAFLD patients and evaluate the possible relationship. Methods: This study included 27 NAFLD patients (10 with nonalcoholic fatty liver (NAFL) and 17 with non-alcoholic steatohepatitis (NASH)) and ten healthy subjects. Total RNA and genomic DNA were extracted from liver tissue samples, and then mtDNA copy number and FGF21 expression levels were assessed by quantitative real-time PCR. Results: The relative level of hepatic mtDNA copy number was 3.9-fold higher in patients than in controls (p < 0.0001). NAFLD patients showed a 2.9-fold increase in hepatic FGF21 expression compared to controls (p < 0.013). Results showed that hepatic FGF21 expression was positively correlated with BMI, serum ALT, and AST levels (p < 0.05). The level of mitochondrial copy number and hepatic FGF21 expression was not significantly associated with stages of change in hepatic steatosis. Finally, there was a significant correlation between FGF21 expression and mitochondrial copy number in NAFLD patients (p = 0.027). Conclusion: Our findings suggest a considerable rise of hepatic FGF21 mRNA levels and mtDNA-CN and show a positive correlation between them in the liver tissue of NAFLD patients.

Tigecycline-Containing Regimens and Multi Drug-Resistant Acinetobacter baumannii: A Systematic Review and Meta-Analysis.

Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR A. baumannii, published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. Results: There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). Conclusions: According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR A. baumannii. However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.

BCG Vaccination and the Risk of Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

(1) Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by progressive and irreversible autoimmune destruction of pancreatic beta cell islets, resulting in absolute insulin deficiency. To date, several epidemiologic and observational studies have evaluated the possible impact of BCG vaccination on T1D development, but the results are controversial. To elucidate this issue, we aimed to conduct a systematic review and meta-analysis of published cohort studies in this field. (2) Methods: A systematic search was performed for relevant studies published up to 20 September 2022 using Pubmed/Medline, Embase, and Scopus. Cohort studies, containing original information about the association between T1D and BCG vaccination, were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the risk ratio of T1D in BCG-vaccinated individuals compared to unvaccinated ones were assessed using the fixed effect model. (3) Results: Out of 630 potentially relevant articles, five cohort studies met the inclusion criteria. The total population of all included studies was 864,582. The overall pooled risk ratio of T1D development in BCG vaccinated and unvaccinated individuals was found to be 1.018 (95% CI 0.908-1.141, I2: 0%). (4) Conclusions: Our study revealed no protective or facilitative effect of prior BCG vaccination in T1D development.

Investigation of cross-reactivity between phenobarbital and levetiracetam in children with epilepsy: A prospective, observational multicenter study.

Objectives: Pharmaceutical allergic reactions due to antiseizure medications (ASMs) are one of the major concerns in the management of patients. Finding an alternative ASM which does not cause allergic reactions and has acceptable effectiveness can be difficult. In this regard, the present study attempts to investigate the cross-reactivity between phenobarbital and levetiracetam in children under treatment for seizure control. Materials & Methods: The present study is a prospective, observational independent assessor study. 30 children with epilepsy who were hypersensitive to phenobarbital therapy were studied. In order to evaluate the cross-reactivity of the drugs, levetiracetam replaced phenobarbital to control seizure. Within 6 months, any allergic reactions and seizure recurrences were evaluated in the patients. Results: 53 % of the children in this study were female. The mean age of patients was 42.4 months. In patients' follow up no cross-reactive responses were observed in any of the patients. Seizure recurrence rate was 30 % in the first six months of follow up that with increasing dosage in the second six months of follow-up, decreased to 10 %. Conclusion: Based on the results of this study, in children with epilepsy controlled by phenobarbital if allergic reactions to phenobarbital occur, levetiracetam may be used as a suitable alternative medicine.

Impact of educational interventions on the prevention of influenza: A systematic review.

Introduction: Seasonal influenza, a contagious viral disease affecting the upper respiratory tract, circulates annually, causing considerable morbidity and mortality. The present study investigates the effectiveness of educational interventions to prevent influenza. Methods: We searched PubMed/Medline, Embase, and Cochrane Controlled Register of Trials (CENTRAL) for relevant clinical studies up to March 1 2022. The following terms were used: "influenza," "flu," "respiratory infection," "prevent," "intervention," and "education." Results: Out of 255 studies, 21 articles satisfied the inclusion criteria and were included in our study: 13 parallel randomized controlled trials (RCT) studies, two cross-over RCT studies, two cohort studies, and four quasi-experimental studies. A total of approximately 12,500 adults (18 years old or above) and 11,000 children were evaluated. Educational sessions and reminders were the most common interventions. The measured outcomes were vaccination rates, the incidence of respiratory tract infection (RTI), and preventive behaviors among participants. Eighteen out of 21 articles showed a significant association between educational interventions and the outcomes. Conclusions: The included studies in the current systematic review reported the efficacy of health promotion educational interventions in improving knowledge about influenza, influenza prevention behaviors, vaccination rates, and decreased RTI incidence regardless of the type of intervention and the age of cases.

Tele-medicine and improvement of mental health problems in COVID-19 pandemic: A systematic review.

INTRODUCTION: Tele-medicine services have been developed in response to the COVID-19 pandemic, which disrupts mental health services. The present study investigates the effectiveness of telephone-delivered services for psychological disorders in the COVID-19 pandemic. METHODS: We searched PubMed/Medline, Embase and Cochrane Controlled Register of Trials for relevant clinical studies up to February 1, 2022. Following terms were used: "severe acute respiratory syndrome", "Coronavirus", "Coronavirus infection", "SARS-CoV-2", "COVID-19", "mental disorder", "mental health", "mental health program", "mental health service", "psychiatric service", "telemedicine", "Telehealth", "Tele-health", "Telecare", "Mobile health". RESULTS: Twelve relevant clinical articles were included in our study. Eight articles were parallel randomized controlled trials (RCTs), two were Quasi-experimental, and one was a multicenter retrospective cohort study. A total of 1900 adults (18 years old or above that) were included. Online telecommunication methods like online apps and videoconference were the most common interventions. The most prevalent measured outcome was levels of anxiety and depression among participants. Eleven out of 12 articles showed a significant association between telemedicine and mental health improvement. CONCLUSIONS: The included studies in the current systematic review reported the probable efficacy of telemedicine in improving mental health disorders during the COVID-19 pandemic. But it is not possible to determine the best telecommunication method for each mental disorder in different populations and the preference of patients is still face to face therapy. So RCTs in different populations with previous mental disorders or chronic diseases are required to investigate the further telemedicine's efficacy on managing mental problems.