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BACKGROUND & AIMS: Clostridium difficile induces intestinal inflammation by releasing toxins A and B. The antimicrobial compound cationic steroid antimicrobial 13 (CSA13) has been developed for treating gastrointestinal infections. The CSA13-Eudragit formulation can be given orally and releases CSA13 in the terminal ileum and colon. We investigated whether this form of CSA13 reduces C difficile infection (CDI) in mice. METHODS: C57BL/6J mice were infected with C difficile on day 0, followed by subcutaneous administration of pure CSA13 or oral administration of CSA13-Eudragit (10 mg/kg/d for 10 days). Some mice were given intraperitoneal vancomycin (50 mg/kg daily) on days 0-4 and relapse was measured after antibiotic withdrawal. The mice were monitored until day 20; colon and fecal samples were collected on day 3 for analysis. Blood samples were collected for flow cytometry analyses. Fecal pellets were collected each day from mice injected with CSA13 and analyzed by high-performance liquid chromatography or 16S sequencing; feces were also homogenized in phosphate-buffered saline and fed to mice with CDI via gavage. RESULTS: CDI of mice caused 60% mortality, significant bodyweight loss, and colonic damage 3 days after infection; these events were prevented by subcutaneous injection of CSA13 or oral administration CSA13-Eudragit. There was reduced relapse of CDI after administration of CSA13 was stopped. Levels of CSA13 in feces from mice given CSA13-Eudragit were significantly higher than those of mice given subcutaneous CSA13. Subcutaneous and oral CSA13 each significantly increased the abundance of Peptostreptococcaceae bacteria and reduced the abundance of C difficile in fecal samples of mice. When feces from mice with CDI and given CSA13 were fed to mice with CDI that had not received CSA13, the recipient mice had significantly increased rates of survival. CSA13 reduced fecal levels of inflammatory metabolites (endocannabinoids) and increased fecal levels of 4 protective metabolites (ie, citrulline, 3-aminoisobutyric acid, retinol, and ursodeoxycholic acid) in mice with CDI. Oral administration of these CSA13-dependent protective metabolites reduced the severity of CDI. CONCLUSIONS: In studies of mice, we found the CSA13-Eudragit formulation to be effective in eradicating CDI by modulating the intestinal microbiota and metabolites.
Assuntos
Antibacterianos/administração & dosagem , Clostridioides difficile/efeitos dos fármacos , Enterocolite Pseudomembranosa/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Esteroides/administração & dosagem , Animais , Fezes/microbiologia , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Vancomicina/administração & dosagemRESUMO
Chronic kidney disease (CKD) causes various complications that significantly impact a patient's overall well-being and quality of life. Sleep disorders are a particularly common issue, especially in patients with advanced disease. This systematic review aims to explore the distinguishing features, prevalence rates, underlying causes, and associated factors related to the most frequent sleep disorders in these patients and present the latest treatment methods for them. It also investigates the link between CKD and sleep disorders and presents the results of the most common sleep disorders found in patients with CKD. Four major sleep disorders have been identified: sleep apnea, restless leg syndrome, excessive drowsiness, and insomnia. These sleep disorders have been discovered to be highly common in CKD patients and have a major influence on their quality of life and morbidity.
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Cardiovascular diseases (CVDs) present a significant global health challenge and remain a primary cause of death. Early detection and intervention are crucial for improved outcomes in acute coronary syndrome (ACS), particularly acute myocardial infarction (AMI) cases. Artificial intelligence (AI) can detect heart disease early by analyzing patient information and electrocardiogram (ECG) data, providing invaluable insights into this critical health issue. However, the imbalanced nature of ECG and patient data presents challenges for traditional machine learning (ML) algorithms in performing unbiasedly. Investigators have proposed various data-level and algorithm-level solutions to overcome these challenges. In this study, we used a systematic literature review (SLR) approach to give an overview of the current literature and to highlight the difficulties of utilizing ML, deep learning (DL), and AI algorithms in predicting, diagnosing, and prognosis of heart diseases. We reviewed 181 articles from reputable journals published between 2013 and June 15, 2023, focusing on eight selected papers for in-depth analysis. The analysis considered factors such as heart disease type, algorithms used, applications, and proposed solutions and compared the benefits of algorithms combined with clinicians versus clinicians alone. This systematic review revealed that the current ML-based diagnostic approaches face several open problems and issues when implementing ML, DL, and AI in real-life settings. Although these algorithms show higher sensitivities, specificities, and accuracies in detecting heart disease, we must address the ethical concerns while implementing these models into clinical practice. The transparency of how these algorithms operate remains a challenge. Nevertheless, further exploration and research in ML, DL, and AI are necessary to overcome these challenges and fully harness their potential to improve health outcomes for patients with AMI.
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A precarious complication of thyrotoxicosis, or thyroid storm, is the increased risk of cardiomyopathy, which leads to circulatory collapse and cardiopulmonary arrest. It is crucial to promptly identify this condition to prevent significant deterioration of the left ventricular function and cardiogenic shock. This article seeks to examine published research that emphasizes the connection between thyroid storm and beta-blocker usage in relation to cardiogenic collapse and provides management recommendations. The search was performed on September 9, 2022, using PubMed, Science Direct, and Google Scholar libraries. A systematic exploration was carried out using the keywords Thyroid Storm AND cardiogenic Shock AND cardiac arrest AND beta blocker. The use of beta blockers as part of thyroid storm management was linked to the development of cardiogenic collapse and cardiac arrest. Ultra-short-acting beta-blockers like esmolol were a safer option than propranolol in treating patients with a thyrotoxic storm.
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Internet gaming and social media usage (SMU), particularly among children and teenagers, have witnessed a remarkable surge over the past decade. However, it remains uncertain whether this widespread usage has a positive or negative impact. The primary objective of this systematic review was to investigate the diverse effects of excessive video game playing and extensive SMU, both favorable and detrimental, on the psychological and mental well-being of children and adolescents. To assess the influence of internet gaming disorder (IGD) and disordered SMU on the mental health of children aged 6-12 years and adolescents aged 13-18 years, we conducted a systematic review of 20 studies on the subject. These studies utilized a substantial sample size of 48,652 participants, encompassing online and in-person questionnaires administered to children, teenagers, and their parents in educational institutions, healthcare facilities, and online platforms. Our findings suggest that multiple factors contribute to the intricate relationship between SMU, video game playing, and mental health outcomes. The majority of research indicates that excessive gaming or SMU among children and teenagers leads to adverse consequences on their mental well-being. Furthermore, certain studies have even reported fatal consequences, while others have identified a worsening of preexisting mental health issues. A few studies have explored the potential positive impacts of SMU and gaming on individuals and society at large. In light of this, we have concluded that it is inappropriate to categorize internet gaming and SMU as solely beneficial or detrimental without considering the broader context and the interplay of various factors.
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Many Crohn's disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used. Colonic FPRL1 mRNA expression was positively correlated with the histology scores of inflammatory bowel disease patients. In CD patients, colonic FPRL1 mRNA was positively correlated with intestinal stricture. CSA13 administration ameliorated intestinal fibrosis without influencing intestinal microbiota. Inhibition of FPRL1, but not suppression of intestinal microbiota, reversed these protective effects of CSA13. Metabolomic analysis indicated increased fecal mevalonate levels in the TNBS-treated mice, which were reduced by the CSA13 administration. CSA13 inhibited colonic HMG-CoA reductase activity in an FPRL1-dependent manner. Mevalonate reversed the anti-fibrogenic effect of CSA13. The increased colonic FPRL1 expression is associated with severe mucosal disease activity and intestinal stricture. CSA13 inhibits intestinal fibrosis via FPRL1-dependent modulation of HMG-CoA reductase pathway.