First use of a new extended reality tool for preoperative planning in coronary artery bypass surgery: a case-report.

A 73-year-old male presented with angina symptoms and was diagnosed with three-vessel coronary artery disease by use of computed tomography angiography and coronary angiography. This diagnosis necessitated coronary artery bypass grafting (CABG) surgery. A custom made AI-driven algorithm was used to generate a patient-specific three-dimensional coronary artery model from computed tomography angiography imaging data. This framework enabled precise segmentation and reconstruction of the coronary vasculature, yielding an accurate anatomical and pathological representation. Subsequently, this generated model was integrated into a novel extended reality tool for preoperative planning and intraoperative guidance in CABG surgery. Both preoperatively and intraoperatively, the tool augmented spatial orientation and facilitated precise stenosis localization, thereby enhancing the surgeon's operative proficiency. This case report underscores the utility of advanced extended reality tools in cardiovascular surgery, emphasizing their pivotal role in refining surgical planning and execution.

Rectal gastrointestinal stromal tumor (GIST) in a patient with Crohn's disease: a rare coincidence case report and brief literature review.

Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors. The most common site for developing these neoplasms is the stomach and small intestine. In contrast, anorectal GISTs are very rare. Population-based studies have shown an increased risk of colorectal cancers (CRC) in patients with Crohn's disease (CD). As in sporadic CRC, adenocarcinomas are the most commonly observed tumor. Accordingly, it is expected that rectal mass in CD patients to be an adenocarcinoma. Some reports have presented CD cases with GISTs along the gastrointestinal tract; however, to the best of our knowledge, a rectal GIST has not been reported in CD. Herein, we report a 41-year-old woman with CD who presented with 8 weeks of constipation and was diagnosed with rectal GIST and briefly review existing reports regarding GIST in IBD.

Design and evaluation of a colon cancer mobile application.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer and the second cause of cancer-related deaths in the world. Despite the infrastructure and the availability of organized screening programs, participation in their screening programs is less than the set goals. Considering the importance of informing the society about the prevention and early detection of colorectal cancer symptoms and the positive impact of mobile health technologies, the present research was conducted with the aim of designing and evaluating a colon cancer mobile application. METHODS: The present research was conducted in two phases: software design and evaluation. In the first phase, the software was prepared using the cascade method. First, all the educational content related to colorectal cancer was collected through an expert panel with the participation of 10 specialists. Then the software was evaluated with alpha and beta testing, and the initial version was approved by users in terms of simplicity and usability. In the second phase, a parallel clinical randomized trial study was conducted with the aim of investigating the effect of a colon cancer mobile application on the early detection of colorectal cancer. In this stage, 204 volunteers participated; inclusion criteria were age 18-85 years, owning a smartphone and the ability to read and write. Participants were randomized into control and intervention groups. The intervention group was educated with the colon cancer application for education about colorectal cancer, and the control group was educated with a pamphlet. After education, both groups were screened for colorectal cancer symptoms, and the results were compared. RESULTS: In the software evaluation phase, the application was used by 204 users. In this stage, 84 (41.2%) women and 120 (58.8%) men, with an average (Standard Deviation) age of 47.53 (13.68) participated. Participants were randomized in two groups, 103 people with an average (Standard Deviation) age of 47.62 (14.65) in intervention group and 101 people with an average (Standard Deviation) age of 47.44 (12.70) in control group. There were no significant differences between the demographic characteristics of age, gender, marriage, occupation, instruction level, digestive disease history, cancer history, cancer risk factors, and family history of cancer between the two groups (P > 0.05). The Mann-Whitney U test indicated that there is a significant difference between the two groups of participants in self-assessment, willingness to do the screening, and the results of the assessment of colorectal cancer (P < 0.05). CONCLUSION: The results of the research indicated the positive impact of the Colon Cancer Application on the abilities of the users of self-assessment of colon cancer. Therefore, based on the findings, it can be concluded that the use of the colon cancer mobile application is effective for colon cancer prevention and self-care. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials ( https://irct.behdasht.gov.ir ) on 13/2/2024, with the IRCT ID: IRCT20210131050189N9.

Application of artificial intelligence in pancreas endoscopic ultrasound imaging- A systematic review.

The pancreas is a vital organ in digestive system which has significant health implications. It is imperative to evaluate and identify malignant pancreatic lesions promptly in light of the high mortality rate linked to such malignancies. Endoscopic Ultrasound (EUS) is a non-invasive precise technique to detect pancreas disorders, but it is highly operator dependent. Artificial intelligence (AI), including traditional machine learning (ML) and deep learning (DL) techniques can play a pivotal role to enhancing the performance of EUS regardless of operator. AI performs a critical function in the detection, classification, and segmentation of medical images. The utilization of AI-assisted systems has improved the accuracy and productivity of pancreatic analysis, including the detection of diverse pancreatic disorders (e.g., pancreatitis, masses, and cysts) as well as landmarks and parenchyma. This systematic review examines the rapidly developing domain of AI-assisted system in EUS of the pancreas. Its objective is to present a thorough study of the present research status and developments in this area. This paper explores the significant challenges of AI-assisted system in pancreas EUS imaging, highlights the potential of AI techniques in addressing these challenges, and suggests the scope for future research in domain of AI-assisted EUS systems.

IL-2RG as a possible immunotherapeutic target in CRC predicting poor prognosis and regulated by miR-7-5p and miR-26b-5p.

Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays a pivotal role as a common subunit receptor in the IL-2 family cytokines and activates the JAK-STAT pathway. This study delves into the role of Interleukin-2 receptor gamma (IL-2RG) within the tumor microenvironment and investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming to discern their impact on CRC clinical outcomes. Bioinformatics analysis revealed a significant upregulation of IL-2RG mRNA in TCGA-COAD samples and showed strong correlations with the infiltration of various lymphocytes. Single-cell analysis corroborated these findings, highlighting IL-2RG expression in critical immune cell subsets. To explore miRNA involvement in IL-2RG dysregulation, mRNA was isolated from the tumor tissues and lymphocytes of 258 CRC patients and 30 healthy controls, and IL-2RG was cloned into the pcDNA3.1/CT-GFP-TOPO vector. Human embryonic kidney cell lines (HEK-293T) were transfected with this construct. Our research involved a comprehensive analysis of miRPathDB, miRWalk, and Targetscan databases to identify the miRNAs associated with the 3' UTR of human IL-2RG. The human microRNA (miRNA) molecules, hsa-miR-7-5p and hsa-miR-26b-5p, have been identified as potent suppressors of IL-2RG expression in CRC patients. Specifically, the downregulation of hsa-miR-7-5p and hsa-miR-26b-5p has been shown to result in the upregulation of IL-2RG mRNA expression in these patients. Prognostic evaluation of IL-2RG, hsa-miR-7-5p, and hsa-miR-26b-5p, using TCGA-COAD data and patient samples, established that higher IL-2RG expression and lower expression of both miRNAs were associated with poorer outcomes. Additionally, this study identified several long non-coding RNAs (LncRNAs), such as ZFAS1, SOX21-AS1, SNHG11, SNHG16, SNHG1, DLX6-AS1, GAS5, SNHG6, and MALAT1, which may act as competing endogenous RNA molecules for IL2RG by sequestering shared hsa-miR-7-5p and hsa-miR-26b-5p. In summary, this investigation underscores the potential utility of IL-2RG, hsa-miR-7-5p, and hsa-miR-26b-5p as serum and tissue biomarkers for predicting CRC patient prognosis while also offering promise as targets for immunotherapy in CRC management.

Barcode lipids for absolute quantitation of liposomes in ocular tissues.

Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an improved understanding of their pharmacokinetics is required, but high-quality in vivo experiments require a large number of animals, raising ethical and economic questions. In order to expedite in vivo kinetic testing of lipid-based systems, we propose a barcode approach that is based on barcoding liposomes with non-endogenous lipids. We developed and evaluated a liquid-chromatography-mass spectrometry method to quantify many liposomes simultaneously in aqueous humor, vitreous, and neural retina at higher than ±20% precision and accuracy. Furthermore, we showed in vivo suitability of the method in pharmacokinetic evaluation of six different liposomes after their simultaneous injection into the rat vitreal cavity. We calculated pharmacokinetic parameters in vitreous and aqueous humor, quantified liposome concentrations in the retina, and quantitated retinal distribution of the liposomes in the rats. Compared to individual injections of the liposome formulations, the barcode-based study design enabled reduction of animal numbers from 72 to 12. We believe that the proposed approach is reliable and will reduce and refine ocular pharmacokinetic experiments with liposomes and other lipid-based systems.

Relationship between workplace spirituality with organization-based self-esteem and workplace deviant behaviors among Iranian nurses.

BACKGROUND: Despite the numerous studies conducted on workplace spirituality, there is still lack of studies that have explored the relationship between workplace spirituality with organization-based self-esteem and workplace deviant behaviors. This study aims to examine the relationship between workplace spirituality with organization-based self-esteem and workplace deviant behaviors among Iranian nurses. METHODS: 236 nurses from 5 hospitals participated in this descriptive, analytical, and cross-sectional study from August to December 2022. Data was gathered by four questionnaires: demographic information, workplace spirituality, organization-based self-steam, and workplace deviant behaviors. The data were analyzed by SPSS 26 based on descriptive and inferential statistics (Independent Two-sample t Test, Pearson correlation coefficient and multiple regression). RESULTS: Based on the findings, nurses had a moderate level of perception of workplace spirituality and organization-based self-esteem while having a low level of perception regarding the occurrence of workplace deviate behaviors. Results of Pearson correlation coefficient test showed a positive and statistically significant relationship between workplace spirituality and organization-based self-esteem. Additionally, there was an inverse and significant relationship between workplace spirituality and organization-based self-esteem with workplace deviant behaviors. Results of multiple regression analyses indicate that by controlling the demographic characteristics of nurses, the meaningful work and sense of community have a significant relationship with organization-based self-esteem. Furthermore, by controlling the demographic characteristics of nurses, permanent employment status, sense of community, alignment with the organization's values, and organization-based self-esteem have a significant relationship with workplace deviant behavior. CONCLUSIONS: The study suggests that organizations must prioritize promoting workplace spirituality and organization-based self-esteem to ensure a healthy work environment and prevent workplace deviant behaviors.

The effectiveness of acceptance and commitment therapy on clinical symptoms and treatment adherence in dialysis patients.

BACKGROUND: Clinical symptoms and treatment adherence are one of the most important problems in dialysis patients. Psychological treatments can be effective in reducing the problems of these patients. Therefore, this study aimed at investigating the effectiveness of acceptance and commitment therapy (ACT) on clinical symptoms and treatment adherence in these patients. MATERIALS AND METHOD: This study was a quasi-experimental study with the experimental and control groups in the dialysis clinic of Torbat-e Heydarieh City in 2012. The sample consisted of 40 people who were referred to the dialysis clinic, and the available sampling method was used to randomly assign participants to the experimental and control groups. In the experimental group, ACT was performed in eight sessions of 90 minutes. Questionnaires of Depression, Anxiety, and Stress Scale (DASS-21) and general adherence scale were used. Data were analyzed using Statistical Package for the Social Sciences (SPSS 21) software and multivariate analysis of covariance (MANCOVA) test. RESULTS: There was a significant difference between the mean scores of clinical symptoms and treatment adherence variables in the experimental and control groups (P < 0.05). The effect of this treatment on reducing the clinical symptoms score was 48%, and on increasing the treatment, the adherence score was 44%. CONCLUSION: ACT can reduce clinical symptoms and increase treatment adherence in dialysis patients, so it is suggested to use this intervention in the design of treatment plans for dialysis patients.

Comprehensive ocular and systemic pharmacokinetics of dexamethasone after subconjunctival and intravenous injections in rabbits.

Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the ocular and plasma pharmacokinetics of subconjunctival dexamethasone in rabbits. Intravenous injection was also given to enable a better understanding of the systemic pharmacokinetics. Dexamethasone concentrations in plasma (after subconjunctival and intravenous injections) and four ocular tissues (iris-ciliary body, aqueous humour, neural retina and vitreous) were analysed using LC-MS/MS. Population pharmacokinetic modelling for plasma data from both injection routes were used, and for first time the constant rate of absorption of dexamethasone from the subconjunctival space into plasma was estimated (ka,plasma = 0.043 min-1, i.e. absorption half-life of 17.3 min). Non-compartmental analysis was used for the ocular data analysis and resulting in ocular drug exposure of iris-ciliary body (AUC0-∞= 41984 min·ng/g) > neural retina (AUC0-∞= 25511 min·ng/g) > vitreous (AUC0-∞= 7319 min·ng/mL) > aqueous humour (AUC0-∞= 6146 min·ng/mL). The absolute bioavailability values after subconjunctival injection, reported for the first time, were 0.74 % in aqueous humour (comparable to topical dexamethasone suspensions), and 0.30 % in vitreous humour (estimated to be higher than in topical administration). These novel and comprehensive pharmacokinetic data provide valuable information on the potential for exploiting this route in ocular drug development for treating both, anterior and posterior segment ocular diseases. Moreover, the new generated dexamethasone-parameters are a step-forward in building predictive pharmacokinetic models to support the design of new subconjunctival dexamethasone formulations, which may sustain drug effect for longer period of time.

Comparing the effectiveness of transdiagnostic treatment with acceptance and commitment therapy on emotional disorders, rumination, and life satisfaction in patients with irritable bowel syndrome: a randomized clinical trial.

OBJECTIVE: The present study was conducted to compare the effectiveness of transdiagnostic treatment (UP) with the acceptance and commitment therapy (ACT) on the emotional disorders, rumination, and life satisfaction in the patients with irritable bowel syndrome (IBS). METHOD: The present study was a randomized clinical trial with a pre-test and post-test design. Between the winter of 2021 and the end of spring 2022, Taleghani Hospital in Tehran received referrals from the statistical population of IBS patients. Of them, 30 individuals (15 in each group) were chosen by convenience sampling and then randomly allocated to groups. UP (It is emotion-based and intervenes in comorbid symptoms), and ACT treatments were provided to the participants online. The participants in the UP and ACT groups received the desired treatments in eight weekly sessions of 45-60 min. RESULTS: There was no significant difference between UP pre-test and ACT regarding depression, anxiety, rumination, and life satisfaction (P > 0.05). There was no significant difference between UP and ACT post-test in terms of depression, rumination, and life satisfaction (P > 0.05), but due to anxiety, their difference was significant (P < 0.05). Besides, there was a significant difference between pre-test and post-test phases of UP and ACT regarding depression, anxiety, and rumination (P < 0.05). Still, they had no significant difference regarding life satisfaction (P > 0.05). CONCLUSION: Therefore, it is suggested that specialists use UP and ACT as effective psychological treatments for the emotional symptoms of IBS patients to improve psychological symptoms.

16S rRNA sequencing analysis of the oral and fecal microbiota in colorectal cancer positives versus colorectal cancer negatives in Iranian population.

BACKGROUND: Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers. MATERIAL AND METHODS: A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform. RESULTS: Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs. CONCLUSION: Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

Anti-inflammatory effects of extracellular vesicles and cell-free supernatant derived from Lactobacillus crispatus strain RIGLD-1 on Helicobacter pylori-induced inflammatory response in gastric epithelial cells in vitro.

Helicobacter pylori infection is the major risk factor associated with the development of gastric cancer. Currently, administration of standard antibiotic therapy combined with probiotics and postbiotics has gained significant attention in the management of H. pylori infection. In this work, the immunomodulatory effects of Lactobacillus crispatus-derived extracellular vesicles (EVs) and cell-free supernatant (CFS) were investigated on H. pylori-induced inflammatory response in human gastric adenocarcinoma (AGS) cells. L. crispatus-derived EVs were isolated by ultracentrifugation and physically characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Furthermore, the protein content of L. crispatus-derived EVs was also evaluated by SDS-PAGE. Cell viability of AGS cells exposed to varying concentrations of EVs and CFS was assessed by MTT assay. The mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, IL-10, and TGF-ß genes was determined by RT-qPCR. ELISA was used for the measurement of IL-8 production in AGS cells. In addition, EVs (50 µg/mL) and CFS modulated the H. pylori-induced inflammation by downregulating the mRNA expression of IL-1ß, IL-6, IL-8, and TNF-α, and upregulating the expression of IL-10, and TGF-ß genes in AGS cells. Furthermore, H. pylori-induced IL-8 production was dramatically decreased after treatment with L. crispatus-derived EVs and CFS. In conclusion, our observation suggests for the first time that EVs released by L. crispatus strain RIGLD-1 and its CFS could be recommended as potential therapeutic agents against H. pylori-triggered inflammation.

Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.

Individuals with Coronavirus Disease 2019 (COVID-19) may show no symptoms to moderate or severe complications. This variation may be due to differences in the strength of the immune response, including a delayed interferon (IFN) response in asymptomatic patients and higher IFN levels in severe patients. Some long non-coding RNAs (lncRNAs), as regulators of the IFN pathway, may contribute to the emergence of different COVID-19 symptoms. This study aimed to comparatively investigate the relationship between lncRNAs (eosinophil granule ontogeny transcript (EGOT), negative regulator of antiviral response (NRAV), and negative regulator of interferon response (NRIR)), alongside interferon-stimulated genes (ISGs) like ISG-15 and interferon-induced transmembrane protein 3 (IFITM3) in COVID-19 patients with asymptomatic, moderate, and severe symptoms. Buffy coat samples were collected from 17 asymptomatic, 23 moderate, 22 severe patients, and 44 healthy controls. Quantitative real-time PCR was utilized to determine the expression levels. In a comparison between COVID-19 patients and healthy individuals, higher expression levels of EGOT and NRAV were observed in severe and moderate patients. NRIR expression was increased across all patient groups. Meanwhile, ISG15 expression decreased in all patient groups, and the moderate group showed a significant decrease in IFITM3 expression. Comparing COVID-19 patient groups, EGOT expression was significantly higher in moderate COVID-19 patients compared to asymptomatic patients. NRAV was higher in moderate and severe patients compared to asymptomatic. NRIR levels did not differ significantly between the COVID-19 patient groups. ISG15 was higher in moderate and severe patients compared to asymptomatic. IFITM3 expression was significantly higher in severe patients compared to the moderate group. In severe COVID-19 patients, EGOT expression was positively correlated with NRAV levels. EGOT and NRAV showed a significant positive correlation in asymptomatic patients, and both were positively correlated with IFITM3 expression. This study suggests that EGOT, NRAV, NRIR, ISG15, and IFITM3 may serve as diagnostic biomarkers for COVID-19. The lncRNA NRAV may be a good biomarker in a prognostic panel between asymptomatic and severe patients in combination with other high-sensitivity biomarkers. EGOT, NRAV, and ISG15 could also be considered as specific biomarkers in a prognostic panel comparing asymptomatic and moderate patients with other high-sensitivity biomarkers.

Biliary co-infection by multidrug-resistant Candida glabrata and Candida albicans in a case of pancreatic cancer with cholangitis: A case report and review of literature.

Herein, we report a case of pancreatic cancer with acute cholangitis secondary to biliary obstruction. Empirical antibiotic therapy did not change the clinical presentation. Blood cultures were sterile; however, bile culture was positive for yeasts. Our laboratory analysis revealed a biliary coinfection by multidrug-resistant C. glabrata and C. albicans. The patient was successfully treated with endoscopic biliary drainage.

Investigating the Impact of Vitamin A and Amino Acids on Immune Responses in Celiac Disease Patients.

Amino acids (AAs) and vitamin imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFß in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. The plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p = 0.04) and an increase in IL-2 (p = 0.008) and IL-12 (p = 0.007) mRNA expression compared to the HCs. The treated adult patients showed elevated Serine (p = 0.003) and Glycine (p = 0.04) levels, as well as increased IL-12 (p < 0.0001) mRNA expression, and a decrease in Tryptophan (p = 0.04) levels relative to the controls. Additionally, the treated adult patients had higher plasma levels of Threonine compared to both the active (p = 0.04) and control (p = 0.02) subjects, and the increased mRNA expression of IL-4 (p = 0.01) in comparison to the active patients. In active children with CD, the IL-2 mRNA level was found to be higher than in the controls (p < 0.0001) and in the treated children (p = 0.005). The treated children with CD exhibited decreased plasma levels of Tryptophan (p = 0.01) and Isoleucine (p = 0.01) relative to the controls, and the increased mRNA expression of TGFß (p = 0.04) relative to the active patients. Elevated levels of specific AAs (Serine, Glycine, Threonine) in the treated CD patients suggested their potential to improve intestinal damage and inflammation, while decreased levels of Tryptophan and Isoleucine highlighted the need for dietary intervention.

Preclinical Models of Cardiac Disease: A Comprehensive Overview for Clinical Scientists.

For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives.

The modulatory effect of Lactobacillus gasseri ATCC 33323 on autophagy induced by extracellular vesicles of Helicobacter pylori in gastric epithelial cells in vitro.

Helicobacter pylori has been recognized as a true pathogen, which is associated with various gastroduodenal diseases, and gastric adenocarcinoma. The crosstalk between H. pylori virulence factors and host autophagy remains challenging. H. pylori can produce extracellular vesicles (EVs) that contribute to gastric inflammation and malignancy. Some probiotic strains have been documented to modulate cell autophagy process. This study was aimed to investigate the modulatory effect of cell-free supernatant (CFS) obtained from Lactobacillus gasseri ATCC 33323 on autophagy induced by H. pylori-derived EVs. EVs were isolated from two clinical H. pylori strains (BY-1 and OC824), and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The viability of AGS cells was assessed after exposure to different concentrations of H. pylori EVs, and L. gasseri CFS. Based on MTT assay and Annexin V-FITC/PI staining, 50 µg/ml of H. pylori EVs and 10 % v/v of L. gasseri CFS were used for further cell treatment experiments. Autophagy was examined using acridin orange (AO) staining, RT-qPCR analysis for autophagy mediators (LC3B, ATG5, ATG12, ATG16L1, BECN1, MTOR, and NOD1), and western blotting for LC3B expression. H. pylori EVs were detected to range in size from 50 to 200 nm. EVs of both H. pylori strains and L. gasseri CFS showed no significant effect on cell viability as compared to untreated cells. H. pylori EVs promoted the development of acidic vesicular organelles and the expression of autophagy-related genes (LC3B, ATG5, ATG12, ATG16L1, BECN1, and NOD1), and decreased the expression of MTOR in AGS cells at 12 and 24 h time periods. In addition, the production of LC3B was increased following 12 h of treatment in AGS cells. In contrast, L. gasseri CFS effectively inhibited EVs-induced autophagy, as evidenced by reduced acidic vesicular organelle formation and modulation of autophagy markers. Our study indicated that L. gasseri CFS can effectively suppress H. pylori EV-induced autophagy in AGS cells. Further investigations are required to decipher the mechanism of action L. gasseri CFS and its metabolites on autophagy inhibition induced by H. pylori.

Atorvastatin Effect on COVID-19 Outcomes: A Propensity Score Matched Study on Hospitalized Patients.

BACKGROUND: This study investigated the association of atorvastatin use on survival, need for intensive care unit (ICU) admission, and length of hospital stay (LOS) among COVID-19 inpatients. MATERIALS AND METHODS: A retrospective study was conducted between March 20th, 2020, and March 18th, 2021, on patients with confirmed COVID-19 admitted to three hospitals in Tehran, Iran. The unadjusted and adjusted effects of atorvastatin on COVID-19 prognosis were investigated. Propensity score matching (PSM) was used to achieve a 1:1 balanced dataset with a caliper distance less than 0.1 and the nearest neighbor method without replacement. RESULTS: Of 4322 COVID-19 patients, 2136 (49.42%) were treated with atorvastatin. After PSM, 1245 atorvastatin inpatients and 1245 controls were included with a median age of 62.0 (interquartile range [IQR]: 51.0, 76.0) and 63.0 (IQR: 51.0, 75.0) years, respectively. The standardized mean differences were less than 0.1 for all confounders, suggesting a good covariate balance. The use of atorvastatin was associated with decreased COVID-19 mortality (HR: 0.80; 95% CI: 0.68-0.95), whereas no relationship was found between atorvastatin and the need for ICU admission (HR: 1.21; 95% CI: 0.99-1.47). LOS was significantly higher in the atorvastatin cohort than controls (Atorvastatin vs. others: 7 [5, 11] vs. 6 [4, 10] days; p = 0.003). The survival rate was higher in combination therapy of atorvastatin plus enoxaparin than in those who received atorvastatin alone (p-value=0.001). CONCLUSION: Atorvastatin may reduce the risk of COVID-19 in-hospital mortality and could be a beneficial option for an add-on therapy. Randomized trials are warranted to confirm the results of the current observational studies.

Modeling the compaction of bacterial chromosomes by biomolecular crowding and the cross-linking protein H-NS.

Cells orchestrate the action of various molecules toward organizing their chromosomes. Using a coarse-grained computational model, we study the compaction of bacterial chromosomes by the cross-linking protein H-NS and cellular crowders. In this work, H-NS, modeled as a mobile "binder," can bind to a chromosome-like polymer with a characteristic binding energy. The simulation results reported here clarify the relative role of biomolecular crowding and H-NS in condensing a bacterial chromosome in a quantitative manner. In particular, they shed light on the nature and degree of crowder and H-NS synergetics: while the presence of crowders enhances H-NS binding to a chromosome-like polymer, the presence of H-NS makes crowding effects more efficient, suggesting two-way synergetics in chain compaction. Also, the results show how crowding effects promote clustering of bound H-NS. For a sufficiently large concentration of H-NS, the cluster size increases with the volume fraction of crowders.