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57, 95% CI = 0.51-2.09, p less then .01). Conclusion In our study cohort LAD and LSSP are highly prevalent anatomical structures within the left atrium. Patients with LSSP showed an approximated 3.5-fold higher probability for ischemic brain alterations. Therefore, LSSP should be considered as a potential risk factor for cardioembolic strokes and its presence should be stated in cardiac CT reports.Background RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. WZB117 purchase Methods RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. Results Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. Conclusions NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.Background The ablation therapy for persistent atrial fibrillation (PerAF) is still a challenge due to the high recurrence rate. This study was aimed to investigate the value of extensive linear ablation with contact force sensing techniques for PerAF. Methods A total of 214 patients with PerAF were enrolled in five centers. The patients were randomly assigned to Group I (PVI + LA roof line+ LA anterior wall line) and Group II (PVI + LA roof line), mitral valve isthmus lines were added in both groups if the atrial fibrillation (AF) could not be terminated after all approaches above. Results Acute success rate of AF termination during the ablation procedure in Group I was significantly higher than Group II (P = 0.028). Two-years follow-up showed no significant difference in the sinus rhythm maintenance rate between the two groups (63.4% in group I vs. 57.2% in group II, P = 0.218). More patients in Group I recurred as organized atrial tachycardia (AT) and can be precisely mapped during repeat ablation procedures (15 vs. 2, P = 0.001). The Kaplan-Meier estimates of AF/AT-free survival after repeat ablation procedures were 76.2% in Group I and 47.1% in Group II (P = 0.039). Conclusions Extensive linear ablation with contact force monitoring did not improve the long-term outcomes for PerAF patients. Repeat ablation procedure showed a possible higher chance of sinus rhythm restoration during follow-up.Every year, complications during pregnancy affect more than 26 million women. Some of those diseases are associated with significant morbidity and mortality, as is the case of preeclampsia, the main cause of maternal deaths globally. The ability to improve the delivery of drugs to the placenta upon administration to the mother may offer new opportunities in the treatment of diseases of pregnancy. The objective of this study was to develop megalin-targeting liposome nanocarriers for placental drug delivery. Megalin is a transmembrane protein involved in clathrin-mediated endocytic processes, and is expressed in the syncytiotrophoblast (SynT), an epithelial layer at maternal-fetal interface. Targeting megalin thus offers an opportunity for the liposomes to hitchhike into the SynT, thus enriching the concentration of any associated therapeutic cargo in the placental tissue. PEGylated (2 KDa) lipids were modified with gentamicin (GM), a substrate to megalin receptors as we have shown in earlier studies, and used eWo monolayers) using flow cytometry. Targeting liposomes containing 5 mol% GM-modified lipids enhanced the uptake of the probe by 1.5 fold compared to the non-targeting control. An increase to 10 mol% of the modified lipid resulted in further enhancement in uptake, which was 2 fold greater compared to control. In a competition assay, inhibition of the megalin receptors resulted in a significant reduction in uptake of the fluorescence probe encapsulated in GM-modified liposomes compared to the uptake without free inhibitor (p less then .0001), implicating the involvement of megalin receptor in the internalization of the liposomes. Taken together, these results demonstrate that megalin-targeted liposomes may offer an opportunity to enhance the delivery of therapeutics to the placenta for the treatment of diseases of pregnancy.Hypoxia is a common feature of the tumor microenvironment, which is characterized by tissue oxygen deficiency due to an aggressive proliferation of cancer cells. Hypoxia activates hypoxia-inducible factor-dependent signaling, which in turn regulates metabolic reprogramming, immune suppression, resistance to apoptosis, angiogenesis, metastasis, and invasion to secondary sites. In this review, we provide an overview of the use of nanotechnology to harmonize intra-tumoral oxygen or suppress hypoxia-related signaling for an improved efficacy of cancer treatment. The biological background was followed by conducting a literature review on the (1) nanoparticles responsible for enhancing oxygen levels within the tumor, (2) nanoparticles sensitizing hypoxia, (3) nanoparticles suppressing hypoxia-inducing factor, (4) nanoparticles that relieve tumor hypoxia for enhancement of chemotherapy, photodynamic therapy, and immunotherapy, either individually or in combination. Lastly, the heterogeneity of cancer and limitations of nanotechnology are discussed to facilitate translational therapeutic treatment.