Melatonin reduces lung injury in type 1 diabetic mice by the modulation of autophagy.

BACKGROUND: In recent years, the role of autophagy has been highlighted in the pathogenesis of diabetes and inflammatory lung diseases. In this study, using a diabetic model of mice, we investigated the expression of autophagy-related genes in the lung tissues following melatonin administration. RESULTS: Data showed histopathological remodeling in lung tissues of the D group coincided with an elevated level of IL-6, Becline-1, LC3, and P62 compared to the control group (p < 0.05). After melatonin treatment, histopathological remodeling was improved D + Mel group. In addition, expression levels of IL-6, Becline-1, LC3, and P62 were decreased in D + Mel compared to D group (P < 0.05). Statistically significant differences were not obtained between Mel group and C group (p > 0.05). CONCLUSION: Our results showed that melatonin injection can be effective in the amelioration of lung injury in diabetic mice presumably by modulating autophagy-related genes.

Consciousness Recovery in Traumatic Brain Injury: A Systematic Review Comparing Modafinil and Amantadine.

OBJECTIVES: Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs. METHODS: This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects. CONCLUSIONS: The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.

Patterns and Predictors of Multimorbidity in the Azar Cohort.

BACKGROUND: The co-existence of chronic diseases (CDs), a condition defined as multimorbidity (MM), is becoming a major public health issue. Therefore, we aimed to determine the patterns and predictors of MM in the Azar Cohort. METHODS: We evaluated the prevalence of MM in 15,006 (35-70-year old) subjects of the Azar Cohort Study. MM was defined as the co-existence of two or more CDs. Data on the subjects' socioeconomic status, demographics, sleeping habits, and physical activity were collected using questionnaires. RESULTS: The overall prevalence of MM was 28.1%. The most prevalent CDs, in decreasing order, were obesity, hypertension, depression, and diabetes. Obesity, depression, and diabetes were the most co-occurring CDs. The MM risk increased significantly with age, illiteracy, and in females. Also, the subjects within the lowest tertile of physical activity level (OR=1.89; 95% CI: 1.75-2.05) showed higher MM risk than those with the highest level of physical activity. Findings regarding current smoking status indicated that being an ex-smoker or smoker of other types of tobacco significantly increased the risk of MM. CONCLUSION: The reduction of MM is possible by promoting public health from an early age among people of various socioeconomic conditions. It is vital to offer the necessary health support to the aging population of Iran.

Insulin resistance is associated with cognitive dysfunction in multiple sclerosis patients: A cross-sectional study.

Multiple sclerosis (MS) is a progressive inflammatory neurodegenerative disease of the nervous system accompanied by demyelination. MS-associated cognitive impairments mainly involve recent memory, information processing speed, stable memory, and executive function. Moreover, MS is associated with impaired glucose and insulin metabolism, which can exacerbate cognitive decline. The present study aimed to compare the cognitive status of MS patients with and without insulin resistance. In this cross-sectional study, 74 relapsing-remitting multiple sclerosis diagnosed patients were enrolled. Indicators of insulin resistance, including fasting blood glucose, insulin level, and homeostatic model assessment of insulin resistance (HOMA-IR) index, were measured. They were then divided into two groups based on the results of the HOMA-IR index. Cognition status was evaluated by the minimal assessment of cognitive function in multiple sclerosis battery. The prevalence of insulin resistance was 37.8%, and the prevalence of cognitive decline was estimated to be 67.56%. Mean scores of the California verbal learning test (CVLT), CVLT delayed free recall, controlled oral word association test, and judgment of line orientation tests were significantly lower in MS patients with insulin resistance than without. In addition, a negative correlation was demonstrated between the results of the CVLT, CVLT delayed free recall, controlled oral word association test, judgment of line orientation tests, brief visuospatial memory test, and Delis-Kaplan executive function system sorting tests and fasting insulin levels. Greater verbal memory and spatial comprehension impairments were observed in MS patients with insulin resistance.

Interventions for decreasing the risk of recurrent IgA nephropathy: A systematic review and meta-analysis.

Recurrent IgA nephropathy (rIgAN) is an important cause of kidney allograft loss. Till now, no proven strategies have been confirmed to prevent/decrease the rIgAN. Here, a systematic review and meta-analysis were performed on the available interventions impacting rIgAN. PubMed, Embase, Web of sciences, ProQuest, and Cochrane library databases along with Google Scholar were searched for articles evaluating the rIgAN after kidney transplantation (up to 23 February 2023). The main inclusion criteria were kidney transplantation because of primary IgAN and articles studying the rate of the rIgAN based on different therapeutic interventions to find their effects on the disease recurrence. Based on our criteria, 11 papers were included in this systematic review, two of which pleased the criteria for the meta-analysis. Meta-analysis showed that the risk of the rIgAN in the steroid-free group was 3.33 times more than that of the steroid-receiving group (Pooled Hazard Ratio = 3.33, 95% CI 0.60 to18.33, Z-value = 1.38, p-value = 0.16). Steroid-free therapy increases the risk of rIgAN in kidney transplant recipients with primary IgAN. High-quality trials with large sample sizes studies are needed to confirm the impact of the steroids on decreasing the rate of the rIgAN.

The Impact of Neutrophil-Lymphocyte Ratio in Febrile Seizures: A Systematic Review and Meta-Analysis.

This meta-analysis was conducted to determine the relationship between neutrophil to lymphocyte ratio (NLR) and febrile seizure (FS). Our study was registered with the PROSPERO (ID: CRD42021259944). Web of Science, Embase, PubMed, Scopus, and ProQuest Central were searched, and finally, 17 studies were included. Standardized mean difference (SMD) was reported with a 95% confidence interval (CI) for the NLR levels. Compared with the febrile control group, the FS patients' NLR levels were significantly higher (SMD = 0.49; 95%CI = 0.26 to 0.72, P < 0.001). Furthermore, we conducted a comparison of NLR levels between febrile controls against simple and complex FS cases separately and found that NLR levels of children with either simple or complex FS were higher compared with those of febrile controls (SMD = 0.42, 95%CI = 0.14 to 0.69, P = 0.003 and SMD = 0.90, 95%CI = 0.71 to 1.09, P < 0.001, respectively). Also, in comparison with the NLR levels of the simple FS group, the complex FS patients' NLR levels were significantly higher (SMD = 0.59, 95%CI = 0.34 to 0.85, P < 0.001). Our study indicated that NLR could be recommended as an inexpensive diagnostic biomarker for FS. In addition, it can be useful when distinguishing between simple FS and complex FS.

Prevalence and Predicting Risk Factors of Polypharmacy in Azar Cohort Population.

Background: As polypharmacy has some medically negative impacts, it has become a challenging issue for public health and affected people. Therefore, we decided to investigate the prevalence of polypharmacy and its predicting risk factors in the Azar cohort population. Methods: In this cross-sectional population-based cohort study, the prevalence of polypharmacy was evaluated in 15,001 subjects who participated in the Azar cohort study. We measured demographic characteristics (age, gender, socioeconomic status, smoking status, marital status, and education level), physical activity level, body mass index (BMI), blood pressure, multimorbidity (coexistence of two or more chronic diseases (CDs)), and polypharmacy status (a daily intake of five or more medicines for a minimum of 90 days). Results: Based on our results, 9.51% of the population had polypharmacy. The five most prescribed medications were drugs acting on the cardiovascular system (19.9%), central nervous system (16.7%), endocrine system (13.3%), NSAIDs (11.5%), and drugs used for musculoskeletal and joint diseases (11.4%). Being female, illiterate, and having the lowest tertile of physical activity level significantly increased the risk of polypharmacy. The risk of polypharmacy was 49.36 times higher in patients with four or more CDs than in those without. Conclusions: Our study emphasized the importance of routine monitoring to evaluate polypharmacy among those aged 35 to 59 and the elderly. Physicians should carefully assess drug suitability, especially in multimorbid and obese patients, to prevent excessive polypharmacy and its potentially negative impacts.

Quality of the Systematic Reviews in Cochrane Gynecological Cancer Group and Their Understudied RCTs.

Purpose: Gynecological cancers are common neoplasms in clinical settings with a high impact on the economy of communities. The medical literature is an essential resource to guide clinical decision-making, and misconduct in researches undermines the credibility and integrity of research in general. We aimed to evaluate the quality of Cochrane gynecological cancers reviews and their understudies RCTS among the different biases dimensions. Methods: This cross-sectional analytical study was performed on 118 systematic reviews published by the Cochrane gynecological cancers Group up to June 2021. The risk of bias was assessed in each Cochrane survey using the Joanna Bridges Institute (JBI) critical assessment tool consisting of 11 questions. The JBI checklist for systematic reviews and research syntheses is available at https://jbi.global/critical-appraisal-tools. After a systematic critical evaluation of the reviews and meta-analysis, we extracted a different bias from all of their understudied RCTs examined in these systematic reviews, which were evaluated by systematic review authors using a standard bias risk tool developed by the Cochrane Group. Results: Cochrane gynecological cancers reviews had high quality based on appraise results using the JBI appraisal checklist. In addition, all of the included studies used PRISMA standards for reporting their results. However, in their understudied RCTs, the most prevalent risk of bias was unclear selection bias (allocation concealment) and performance bias (blinding of participants and personnel). Also, the highest risk of bias was blinding participants and personnel (performance bias) and incomplete outcome data (attrition bias). Our results showed that the lowest risk of bias was incomplete outcome data (attrition bias) and random sequence generation (selection bias). Conclusion: Although most Cochrane gynecological cancers reviews had high quality, unclear performance bias was the highest in their understudied RCTs, indicating structural deficiencies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-022-01655-6.

Systematic Review and Meta-analysis of TP53, HER2/ERBB2, KRAS, APC, and PIK3CA Genes Expression Pattern in Gastric Cancer.

Background: With a global prevalence of about 10%, gastric cancer is among the most prevalent cancers. Currently, there has been an ongoing trend toward investigating genetic disruptions in different cancers because they can be used as a target-specific therapy. We aimed to systemically review some gene expression patterns in gastric cancer. Methods: The current systematic review was designed and executed in 2020. Scopus, PubMed, Cochrane Library, Google Scholar, web of knowledge, and Science Direct were searched for relevant studies. A manual search of articles (hand searching), reference exploring, checking for grey literature, and seeking expert opinion were also done. Results: In this review, 65 studies were included, and the expression pattern of HER2/ ERBB2, ER1/Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, FGFR2 and MET was investigated. TP53, APC, KRAS, and PIK3CA mutation cumulative frequency were 24.8 (I2=95.05, Q value=525.53, df=26, P<0.001), 7.2 (I2=89.79, Q value=48.99, df=5, P<0.001), 7.8 (I2=93.60, Q value=140.71, df=9, P=0.001) and 8.6 (I2=80.78, Q value=525.53, df=9, P<0.001) percent, respectively. Overexpression was investigated for HER1/ Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, CCND1, FGFR2, MET and MYC. The frequency of TP53 and HER2/ERBB2 were 43.1 (I2=84.06, Q value=58.09, df=9, P<0.001) and 20.8 (I2=93.61, Q value=234.89, df=15, P<0.001) percent, respectively. Conclusion: More research is encouraged to investigate the genes for which we could not perform a meta-analysis.

Systematic Review and Meta-analysis of the Most Common Genetic Mutations in Esophageal Squamous Cell Carcinoma.

PURPOSE: Esophageal cancer is the second most common cancer among men and women. There is a need to systematically assess the current evidence to map out the contribution of genetic factors in the development of esophageal squamous cell carcinoma (ESCC). METHODS: A literature search was carried out on published and unpublished studies up to August 2021 in Medline (PubMed), Embase (Ovid), Scopus, Proquest, Web of Science, and Google scholar. Studies that have reported the frequency of genetic mutations in ESCC were included in this study. RESULTS: A total of 1238 titles were retrieved through searches, and finally, 56 articles, including 8114 samples, met our predefined inclusion criteria. Of the included studies, 31 were conducted in China, 12 in Japan, and the remaining were conducted in various nations, including Brazil, Korea, and Iran. Most of our included studies evaluated the TP53 (n = 37 studies) and PIK3CA (n = 30 studies) gene mutations. TP53 (68.6%; 95% CI: 61.6-74.9), CCND1 (39.3%; 95% CI: 26.2-54.1), MDM2 (24.9%; 95% CI: 9.5-51.0), NOTCH1/2/3 (17.9%; 95% CI: 15.0-21.2), KMT2D (17.4%; 95% CI: 12.4-23.8), CDKN2A (15.0%; 95% CI: 8.1-26.1), PIK3CA (13.8%; 95% CI: 10.3-18.1), FAT1 (13.3%; 95% CI: 11.7-15.0), and EGFR (9.9%; 95% CI: 5.6-17.0) were the most common involved genetic factors in developing ESCC. CONCLUSION: This systematic review and meta-analysis revealed that more than 10% of ESCC patients had changes in TP53, CCND1, MDM2, NOTCH1/2/3, KMT2D, CDKN2A, PIK3CA, and FAT1 genes, which can highlight their role in developing ESCC. TP53, CCND1, and MDM2 are the most prevalent, demonstrating 68.6%, 39.3%, and 24.9% of the mutations in ESCC patients.

Acute pancreatitis in a young woman with COVID-19 infection: A case-report.

BACKGROUND: Little is known about the development of acute pancreatitis as a complication of corona virus disease of 2019 (COVID-19) infection. This case report describes the presentation of acute pancreatitis in a young woman who then was diagnosed with COVID-19 infection. CASE PRESENTATION: An 18-year old previously healthy woman referred to Imam Raza hospital, Tabriz, Iran with a 3-day history of intermittent and crampy abdominal pain. She had serum amylase of 1288 IU/L and serum lipase of 1541 IU/L. She was diagnosed with acute pancreatitis. She was instructed nil per os (NPO) and serum therapy and also was given pantoprazole, and pethidine for her pain management. The laboratory tests for assessing the etiology of acute pancreatitis were normal. Abdominal and pelvic spiral computed tomography (CT) scan revealed edematous pancreas and enhancing loculi fluid accumulation around pancreas along with the small amount of ascites fluid that all suggest acute pancreatitis. Due to the presentation of fever and COVID-19 pandemic and her potential society exposure, we tested SARS CoV-2 by polymerase chain reaction which was positive. The blood C-reactive protein (CRP) level was 3+ but the chest x-ray showed no findings compatible with COVID-19. Eventually after receiving conservative therapy for her pancreatitis, she was discharged from hospital in the good general condition and she has not experienced any episodes of abdominal pain again. CONCLUSION: This case highlights acute pancreatitis as a suspected complication associated with COVID-19 and the need for further research.