RESUMEN
Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans.
Asunto(s)
Células-Madre Neurales/metabolismo , Neurogénesis/genética , Neuronas/metabolismo , Telómero/fisiología , Proteína 2 de Unión a Repeticiones Teloméricas/fisiología , Animales , Conducta Animal , Diferenciación Celular/genética , Regulación del Desarrollo de la Expresión Génica , Ratones , Ratones Noqueados , Neuronas/citología , Transmisión Sináptica/genéticaRESUMEN
PURPOSE: To compare the port infection rate between single-lumen (SL) and double-lumen (DL) ports and to determine whether the use of a DL port is an independent risk factor for port infection among patients with cancer. MATERIALS AND METHODS: This retrospective study included 2,573 adult oncologic patients (aged >18 years) who had either a SL (n = 841) or a DL (n = 1,732) chest port implanted between 2013 and 2020 at a single institution. Patients who had port infection, including port-site infection and port-related bloodstream infection, were identified through chart review. After propensity score matching based on 13 potentially confounding variables, a total of 493 pairs of patients with either SL (SL group) or DL (DL group) ports were subjected to analysis. The port infection rate was compared between the 2 groups using Poisson regression. Multivariate proportional subdistribution hazards regression (PSHREG) analysis was conducted to determine whether use of a DL port is an independent risk factor for port infection. RESULTS: The cumulative follow-up period for the matched cohort was 371,853 catheter-days (median, 297 catheter-days per port; range, 0-1,903 catheter-days). The port infection rate of the DL group was significantly higher than that of the SL group (0.232 vs 0.113 infections per 1,000 catheter-days; P = .001). PSHREG analysis demonstrated that use of a DL port was an independent risk factor of port infection (subdistribution hazard ratio, 2.30; 95% CI, 1.33-3.78; P = .002). CONCLUSIONS: DL ports were associated with a higher risk of port infection compared with SL ports in adult oncologic patients.