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1.
J Am Vet Med Assoc ; : 1-7, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688327

RESUMO

OBJECTIVE: To determine whether student involvement in intravenous catheter (IVC) placement increases the risk for complications and to report the rate and types of complications associated with IVCs in adult horses in a university teaching hospital. ANIMALS: 455 IVCs placed in 394 horses. METHODS: Data relevant to IVC placement and removal were retrieved from an electronic medical record search including records of adult horses from January 1 to December 31, 2022. Data retrieved from records included the role of the individual who prepared the site and placed the IVC, site of IVC placement, and type of IVC. The reason for removal of the IVC and presence or absence of detectable changes within the vein at the time of removal were documented in addition to clinical data, allowing for classification of each case. Data were reviewed retrospectively, and statistical analyses were performed using mixed-effects logistic regression models. Significance was set at P ≤ .05. RESULTS: The overall rate of complications was 15.6%, and the most common type of complication was swelling of the vein. Students were involved in 87 of 455 IVC site preparations and placements, and there were no statistically significant differences in complication rates between IVC sites prepared or placed by veterinary students versus nonstudent personnel. CLINICAL RELEVANCE: Veterinary personnel and clients may be hesitant to allow student involvement in IVC placement in horses, but these data suggest that student involvement does not increase the risk of IVC complications.

2.
Nat Commun ; 15(1): 2165, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461301

RESUMO

The telomere repeat-containing RNA (TERRA) forms R-loops to promote homology-directed DNA synthesis in the alternative lengthening of telomere (ALT) pathway. Here we report that TERRA contributes to ALT via interacting with the lysine-specific demethylase 1A (LSD1 or KDM1A). We show that LSD1 localizes to ALT telomeres in a TERRA dependent manner and LSD1 function in ALT is largely independent of its demethylase activity. Instead, LSD1 promotes TERRA recruitment to ALT telomeres via RNA binding. In addition, LSD1 and TERRA undergo phase separation, driven by interactions between the RNA binding properties of LSD1 and the G-quadruplex structure of TERRA. Importantly, the formation of TERRA-LSD1 condensates enriches the R-loop stimulating protein Rad51AP1 and increases TERRA-containing R-loops at telomeres. Our findings suggest that LSD1-TERRA phase separation enhances the function of R-loop regulatory molecules for ALT telomere maintenance, providing a mechanism for how the biophysical properties of histone modification enzyme-RNA interactions impact chromatin function.


Assuntos
Neoplasias , Estruturas R-Loop , RNA Longo não Codificante , Homeostase do Telômero , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Separação de Fases , RNA Longo não Codificante/genética , Telômero/genética , Telômero/metabolismo , Homeostase do Telômero/genética , Humanos
3.
Am J Physiol Gastrointest Liver Physiol ; 326(3): G228-G246, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38147796

RESUMO

Ischemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGCs) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network density and glial activity were examined by Gene Set Enrichment Analysis, three-dimensional (3-D) volume imaging, and Western blot and its function in regulating epithelial restitution was assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate (FA), and in vitro by coculture assay. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete lack of coordinated reparative signaling in the mucosal microenvironment. Furthermore, we report important evidence that the subepithelial EGC network changes significantly over the early postnatal period and demonstrate that the proximity of a specific functional population of EGC to wounded intestinal epithelium contributes to intestinal barrier restitution following ischemic injury.NEW & NOTEWORTHY This study refines a powerful translational pig model, defining an age-dependent relationship between enteric glia and the intestinal epithelium during intestinal ischemic injury and confirming an important role for enteric glial cell (EGC) activity in driving mucosal barrier restitution. This study suggests that targeting the enteric glial network could lead to novel interventions to improve recovery from intestinal injury in neonatal patients.


Assuntos
Intestino Delgado , Neuroglia , Humanos , Animais , Recém-Nascido , Suínos , Neuroglia/fisiologia , Intestinos , Mucosa Intestinal , Jejuno , Isquemia
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