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Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal tract. Extracellular adenosine triphosphate (eATP) produced by the commensal microbiota and host cells activates purinergic signaling, promoting intestinal inflammation and pathology. Based on the role of eATP in intestinal inflammation, we developed yeast-based engineered probiotics that express a human P2Y2 purinergic receptor with up to a 1,000-fold increase in eATP sensitivity. We linked the activation of this engineered P2Y2 receptor to the secretion of the ATP-degrading enzyme apyrase, thus creating engineered yeast probiotics capable of sensing a pro-inflammatory molecule and generating a proportional self-regulated response aimed at its neutralization. These self-tunable yeast probiotics suppressed intestinal inflammation in mouse models of IBD, reducing intestinal fibrosis and dysbiosis with an efficacy similar to or higher than that of standard-of-care therapies usually associated with notable adverse events. By combining directed evolution and synthetic gene circuits, we developed a unique self-modulatory platform for the treatment of IBD and potentially other inflammation-driven pathologies. A synthetic yeast-based therapeutic that secretes an ATP-degrading enzyme in response to pro-inflammatory extracellular ATP in the gut reduces intestinal inflammation, fibrosis and dysbiosis in mouse models of colitis and enteritis., Author(s): Benjamin M. Scott [sup.1] [sup.2] [sup.3] [sup.9] , Cristina Gutiérrez-Vázquez [sup.4] , Liliana M. Sanmarco [sup.4] , Jessica A. da Silva Pereira [sup.4] , Zhaorong Li [sup.4] , Agustín [...]

Introduction. Implementation of the Enhanced Recovery After Surgery (ERAS) protocol has been shown to improve outcomes in colorectal surgery. In Colombia, its implementation is scarce and there is limited evidence of its benefits. For this reason, the objective of this study was to evaluate the effect of ERAS protocol implementation in patients undergoing colorectal surgery in a reference hospital in Southwestern Colombia. Methods. Observational study with ideal clinical experiment emulation approach. Adult patients undergoing major colorectal surgery between 2021 and 2023 were included. Days of hospital stay, admission to the intensive care unit (ICU), and the presence of overall complications, reinterventions, or hospital readmission within 30 days were measured. A univariate and multivariate analysis was performed to measure the effect of the implementation of the ERAS protocol on the outcomes. Results. A total of 132 patients met the inclusion criteria, 79 patients in the period prior to ERAS implementation and 53 patients with the ERAS protocol. In the multivariate analysis, a relative reduction of 77% for ICU admissions, 57% for overall complications, 67% for hospital readmission, and 92% for surgical reinterventions after discharge in ERAS patients was found. Conclusions. Implementation of ERAS recommendations at our institution was shown to improve clinical outcomes in patients undergoing major colorectal surgery, In Colombia, multicenter studies are needed to demonstrate the plausibility and benefits of these recommendations in other institutions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common type and accounts for 60%–70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non‐coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD‐related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO—Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA‐30a‐3p, miRNA‐193a‐5p, miRNA‐143‐3p, miRNA‐145‐5p. The pathways epidermal growth factor, MAPK, TGF‐beta and ATM‐dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD. [ABSTRACT FROM AUTHOR]

In this study, an extensive analysis of microsatellite markers (Single Tandem Repeats—STRs) in Penaeus vannamei was conducted at an advanced level. The markers were thoroughly examined, characterized, and specific markers located within coding regions were identified. Out of a total of 306 STRs, 117 were classified as perfect markers based on their single repeat motif. Among these perfect markers, 62 were found to be associated with predicted coding genes (mRNA), which were involved in various functions such as binding, catalytic activity, ATP-dependent activity, transcription, structural and molecular regulation. To validate the accuracy of the findings, a sample of nine markers was subjected to in vitro testing, which confirmed the presence of polymorphisms within the population. These results suggest the existence of different protein isoforms within the population, indicating the potential of these markers for application in both population and phenotype-genotype association studies. This innovative approach opens up new possibilities for investigating the impact of genomic plasticity in populations of P. vannamei. [ABSTRACT FROM AUTHOR]