Interaction of Glia Cells with Glioblastoma and Melanoma Cells under the Influence of Phytocannabinoids

Brain tumor heterogeneity and progression are subject to complex interactions between tumor cells and their microenvironment. Glioblastoma and brain metastasis can contain 30–40% of tumor-associated macrophages, microglia, and astrocytes, affecting migration, proliferation, and apoptosis. Here, we analyzed interactions between glial cells and LN229 glioblastoma or A375 melanoma cells in the context of motility and cell–cell interactions in a 3D model. Furthermore, the effects of phytocannabinoids, cannabidiol (CBD), tetrahydrocannabidiol (THC), or their co-application were analyzed. Co-culture of tumor cells with glial cells had little effect on 3D spheroid formation, while treatment with cannabinoids led to significantly larger spheroids. The addition of astrocytes blocked cannabinoid-induced effects. None of the interventions affected cell death. Furthermore, glial cell-conditioned media led to a significant slowdown in collective, but not single-cell migration speed. Taken together, glial cells in glioblastoma and brain metastasis micromilieu impact the tumor spheroid formation, cell spreading, and motility. Since the size of spheroid remained unaffected in glial cell tumor co-cultures, phytocannabinoids increased the size of spheroids without any effects on migration. This aspect might be of relevance since phytocannabinoids are frequently used in tumor therapy for side effects

Left atrial appendage closure outcomes in relation to atrial fibrillation patterns: a comprehensive analysis

ObjectiveThe effect of atrial fibrillation (AF) patterns on outcomes remains controversial. This study aims to evaluate the influence of AF type on the risk of cardiocerebrovascular events after left atrial appendage closure (LAAC) at long-term follow-up.MethodsAF was categorized as paroxysmal AF (PAF) and non-PAF (NPAF). The baseline characteristics, procedural data, peri-procedural complications, and long-term outcomes between patients with PAF and NPAF after LAAC were compared.ResultsWe analyzed 410 AF patients (mean age 74.8 ± 8.2 years; 271 male; 144 with PAF, 266 NPAF). The NPAF group tended to be older (≥75 years), male, and have chronic kidney disease (CKD) compared with the PAF group. The procedural data and peri-procedural complications were comparable. During 2.2 ± 1.5 years of follow-up, the incidences of thromboembolism, major bleeding, and device-related thrombus (DRT) did not differ between the two groups. The observed risk of thromboembolism and major bleeding was significantly lower than the estimated risk based on the CHA2DS2-VASc and HAS-BLED scores, respectively, in patients who underwent LAAC, regardless of the AF type. NPAF patients were associated with a higher risk of all-cause mortality, non-cardiovascular mortality, and combined efficacy endpoints. This association disappeared after propensity score matching (PSM) analysis.ConclusionsThe risk of thromboembolism and major bleeding was lower in patients who underwent LAAC, regardless of the AF type. Although NPAF often coexists with multiple risk factors, it was not associated with worse long-term outcomes after LAAC when compared with PAF

Hypersomnolence and Sleep-related Complaints in Metropolitan, Urban, and Rural Georgia

Persistent daytime hypersomnolence is associated with significant morbidity and mortality, but its prevalence in the population has been poorly documented. This study sought to characterize the prevalence of persistent daytime hypersomnolence, difficulties initiating and maintaining sleep, unrefreshing sleep, snoring, and the presence of physician-diagnosed sleep disorders in metropolitan, urban, and rural US Georgia populations. Between September 2004 and July 2005, a total of 6,530 randomly selected well and unwell adults, identified by screening interviews of 10,837 households (contacted by random digit dialing), completed a detailed phone interview. Sixteen percent reported persistent problems staying awake during the day; 26% reported persistent problems falling asleep at night; 31% experienced problems sleeping through the night; 34% were bothered by unrefreshing sleep; and 33% reported that they snored. In spite of the high occurrence of reported persistent sleep problems, only 10% of the survey participants reported having been diagnosed with a sleep disorder. These study findings highlight the need for increased public and clinician awareness with respect to proactively indentifying signs and symptoms of sleep disorders, a better understanding of their adverse impact upon morbidity and mortality, and their negative impact upon socioeconomic and academic potential

Die Hydratisierung der Brenztraubensaeure in Mikroemulsionen

Walsleben A. Die Hydratisierung der Brenztraubensaeure in Mikroemulsionen. Bielefeld; 1984