EZH2-interacting lncRNAs contribute to gastric tumorigenesis; a review on the mechanisms of action.

Gastric cancer (GC) remains one of the deadliest malignancies worldwide, demanding new targets to improve its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are dysregulated through gastric tumorigenesis and play a significant role in GC progression and development. Recent studies have revealed that lncRNAs can interact with histone-modifying polycomb protein, enhance Zeste Homolog 2 (EZH2), and mediate its site-specific functioning. EZH2, which functions as an oncogene in GC, is the catalytic subunit of the PRC2 complex that induces H3K27 trimethylation and epigenetically represses gene expression. EZH2-interacting lncRNAs can recruit EZH2 to the promoter regions of various tumor suppressor genes and cause their transcriptional deactivation via histone methylation. The interactions between EZH2 and this lncRNA modulate different processes, such as cell cycle, cell proliferation and growth, migration, invasion, metastasis, and drug resistance, in vitro and in vivo GC models. Therefore, EZH2-interacting lncRNAs are exciting targets for developing novel targeted therapies for GC. Subsequently, this review aims to focus on the roles of these interactions in GC progression to understand the therapeutic value of EZH2-interacting lncRNAs further.

High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry.

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.

Superior mesenteric artery thrombosis with concomitant pancreaticoduodenal artery pseudoaneurysm in a 60-year-old male patient - A case report.

INTRODUCTION: Vascular complications like superior mesenteric artery (SMA) thrombosis and pancreaticoduodenal artery (PDA) pseudoaneurysm carry high morbidity and mortality. SMA provides the primary arterial supply to the small intestine and ascending colon. PDA aneurysms are extremely rare, accounting for only 2 % of all visceral artery aneurysms. We present a rare case of SMA thrombosis with concomitant PDA pseudoaneurysm. CASE PRESENTATION: Herein is the case of a 60-year-old male who presented with rectorrhagia, persistent generalized abdominal pain. After being diagnosed with colitis and mesenteric artery thrombosis based on a computed tomography (CT) scan, he was discharged from the hospital with rivaroxaban and mesalazin. However, he had to return to the hospital due to worsening of the symptoms. After a proper workout, SMA artery thrombosis with a concomitant PDA pseudoaneurysm was diagnosed for him. Therefore, he underwent surgery to stent the thrombosis and coil the pseudoaneurysm. His symptoms dramatically improved after the treatment. DISCUSSION: Angiography is the diagnostic and, with embolization, therapeutic procedure of choice, with surgery as a backup if embolization fails. However, even with these procedures, the mortality rate is high if the pseudoaneurysm ruptures. CONCLUSION: In order to carry out the proper choice of surgical treatment before further complications occur, SMA thrombosis and PDA pseudoaneurysms must be investigated in each patient presenting with nonspecific abdominal pain, regardless of the risk factors.

Nivolumab plus ipilimumab combination therapy in cancer: Current evidence to date.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy, yielding significant antitumor responses across multiple cancer types. Combination ICI therapy with anti-CTLA-4 and anti-PD-1 antibodies outperforms either antibody alone in terms of clinical efficacy. As a consequence, the U.S. Food and Drug Administration (FDA) approved ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) as the first-ever approved therapies for combined ICI in patients with metastatic melanoma. Despite the success of ICIs, treatment with checkpoint inhibitor combinations poses significant clinical challenges, such as increased rates of immune-related adverse events (irAEs) and drug resistance. Thus, identifying optimal prognostic biomarkers could help to monitor the safety and efficacy of ICIs and identify patients who may benefit the most from these treatments. In this review, we will first go over the fundamentals of the CTLA-4 and PD-1 pathways, as well as the mechanisms of ICI resistance. The results of clinical findings that evaluated the combination of ipilimumab and nivolumab are then summarized to support future research in the field of combination therapy. Finally, the irAEs associated with combined ICI therapy, as well as the underlying biomarkers involved in their management, are discussed.

Fulminant psudeumonas pneumonia following coronary artery bypass grafting - Case report.

INTRODUCTION AND IMPORTANCE: Pneumonia has always been a source of complication after surgeries. Pseudomonas aeruginosa has emerged as one of the most problematic Gram-negative pathogens among nosocomial infections. Pneumonia caused by pseudomonas is usually slowly progressive allowing clinicians to detect and manage it on time. CLINICAL PRESENTATION: A 55-year-old man was hospitalized for elective CABG, complicated by fulminant pneumonia. Vancomycin and meropenem were adminestered as soon as the symptoms appeared. However, the patient died from septic shock syndrome caused by pseudomonas pneumonia on the third postoperative day, just hours after the first symptom appeared. The chest X-ray showed an extreme opacity within less than 12 h. CLINICAL DISCUSSION: This case is reported because of its rare clinical presentation of Fulminant pseudomonas pneumonia following cardiac surgery. CONCLUSION: Consider pseudomonas aeruginosa as a certain cause of pneumonia after cardiac surgery, and an organized, modified guideline is needed to determine the best option and timeline for treating this complication.

Designing and Evaluation of an Elective Oral Health Course for Fifth-Year Medical Students of Tehran University of Medical Sciences.

Objectives: This study aimed to evaluate the effect of an educational intervention on oral health-related knowledge, attitude, and practice of medical students. Materials and Methods: This study was performed on the fifth-year medical students attending an elective oral health course at the Faculty of Dentistry of Tehran University (intervention group) and 25 other students attending another elective course (control group) in 2018. A 2-week internship program including 6 sessions of a workshop program plus 2 days of school field and 2 days of attending dental departments was designed for the intervention group. Before and after the intervention, students completed a questionnaire and their simplified debris index was calculated. Statistical analysis was performed using SPSS version 24 by paired-sample t-test and general linear regression. Results: The mean age of the participants was 24.84±1.31 years in the intervention group and 23.64±1.28 years in the control group. There were 14 (56%) males in the intervention group and 16 (64%) males in the control group. At baseline, the mean knowledge, attitude and practice scores of the control and intervention groups were 26.28, 14.20 and 10.88, and 27.84, 15.80, and 9.36, respectively. After the intervention, the knowledge, attitude, debris index and willingness to adhere to oral health measures significantly improved (P<0.05). Conclusion: Oral health-related knowledge, attitude and practice of medical students were not desirable at baseline. The present study showed that even a short-term intervention in this field was effective to improve the oral health concepts in this group.

Clonidine Versus Chloral Hydrate for Recording Sleep EEG in Children.

OBJECTIVE: One of the difficulties to conduct electroencephalography (EEG) in pediatric patient population is that they are not always cooperative during the procedure. Different medications are used to induce sedation during EEG recording. In order to find a medication with the least adverse effects and high efficacy, the current study aimed at comparing clonidine and chloral hydrate as a premedication prior to EEG recording in pediatric population. MATERIALS & METHODS: A prospective, randomized, single-blinded, controlled trial was conducted on 198 children (9 to 156 months old) to investigate the sedative and adverse effects of clonidine and chloral hydrate. Patients, partially sleep-deprived the night before, were randomly divided into two groups of clonidine (n=100) and chloral hydrate (n=98) on an alternative day basis. RESULTS: The average sleep onset latency was significantly longer in the clonidine group than chloral hydrate group (the Mann-Whitney test, p <0.0001). Sleep duration ranged 15 to 150 minutes and it was not significantly different between the two groups (the Mann-Whitney test, p = 0.2). Drowsiness terminated faster with chloral hydrate than clonidine.Drowsiness after arousal was observed in 58% and 26.1% of patients in the clonidine and chloral hydrate groups, respectively; the difference between the groups was significant (the Mann-Whitney test, p = 0.058). EEG results were reported normal in 77 subjects in the chloral hydrate group (77%) and 69 subjects (69%) in the clonidine group (p = 0.161). Generalized epileptiform discharges were significant in the clonidine group (the Mann-Whitney test, p = 0.006). CONCLUSION: The results of the current study showed that both 5% chloral hydrate (1 mL/kg) and clonidine (4 µg/kg) could be administered as a premedication prior to EEG recording in children, although drowsiness after arousal was higher with clonidine than chloral hydrate. However, the yield of generalized epileptiform discharges in the clonidine group was greater than that of the chloral hydrate group.

Association between iron deficiency anemia and Helicobacter pylori infection among children under six years in Iran.

This study was conducted to evaluate the association between H. pylori infection and Iron deficiency anemia (IDA) among preschool children (age range: 40-75 months) at a tertiary referral hospital in Tehran.In a case-control study, the prevalence of H. pylori seropositivity was compared between 64 children with IDA diagnosis and 70 healthy non-anemic sex- and age-matched controls. Totally, 52 (81.3%) children with IDA and 10 (14.3%) non-anemic controls had a positive antibody level for H. pylori specific IgG and the difference between two groups was statistically significant (P<0.0001). H. pylori infection had a significant high prevalence among preschool patients with IDA. Eradication of H. pylori infection is recommended for patients with refractory IDA.