Folic Acid Functionalized Nanoparticles for Enhanced Oral Drug Delivery

The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle-encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface-functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5-fold increase in apparent permeability (P(app)) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid-functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability

Lack of association between dual antiplatelet therapy use and stent thrombosis between 1 and 12 months following resolute zotarolimus-eluting stent implantation

Aim The optimal duration of dual antiplatelet therapy (DAPT) following the use of new generation drug-eluting stents is unknown. Methods and results The association between DAPT interruption and the rates of stent thrombosis (ST) and cardiac death/target-vessel myocardial infarction (CD/TVMI) in patients receiving a Resolute zotarolimus-eluting stent (R-ZES) was analysed in 4896 patients from the pooled RESOLUTE clinical programme. Daily acetylsalicylate (ASA) and a thienopyridine for 6-12 months were prescribed. A DAPT interruption was defined as any interruption of ASA and/or a thienopyridine of >1 day; long interruptions were >14 days. Three groups were analysed: no interruption, interruption during the first month, and >1-12 months. There were 1069 (21.83%) patients with a DAPT interruption and 3827 patients with no interruption. Among the 166 patients in the 1-month interruption group, 6 definite/probable ST events occurred (3.61%; all long DAPT interruptions), and among the 903 patients in the >1-12 months (60% occurred between 6 and 12 months) interruption group, 1 ST event occurred (0.11%; 2-day DAPT interruption). Among patients with no DAPT interruption, 32 ST events occurred (0.84%). Rates of CD/TVMI were 6.84% in the 1-month long interruption group, 1.41% in the >1-12 months long interruption group, and 4.08% in patients on continuous DAPT. Conclusion In a pooled population of patients receiving an R-ZES, DAPT interruptions within 1 month are associated with a high risk of adverse outcomes. Dual antiplatelet therapy interruptions between 1 and 12 months were associated with low rates of ST and adverse cardiac outcomes. Randomized clinical trials are needed to determine whether early temporary or permanent interruption of DAPT is truly safe. Clinical Trials.gov identifiers NCT00617084; NCT00726453; NCT00752128; NCT0092794

TCT-260 Which is the Ideal Revascularization Strategy in Patients Presenting with Acute Coronary Syndrome and Proximal LAD Stenosis? Results from the ACUITY Study

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Mechanical Circulatory Support for Right Ventricular Failure

Right ventricular (RV) failure is associated with significant morbidity and mortality, with in-hospital mortality rates estimated as high as 70–75%. RV failure may occur following cardiac surgery in conjunction with left ventricular failure, or may be isolated in certain circumstances, such as inferior MI with RV infarction, pulmonary embolism or following left ventricular assist device placement. Medical management includes volume optimisation and inotropic and vasopressor support, and a subset of patients may benefit from mechanical circulatory support for persistent RV failure. Increasingly, percutaneous and surgical mechanical support devices are being used for RV failure. Devices for isolated RV support include percutaneous options, such as micro-axial flow pumps and extracorporeal centrifugal flow RV assist devices, surgically implanted RV assist devices and veno-arterial extracorporeal membrane oxygenation. In this review, the authors discuss the indications, candidate selection, strategies and outcomes of mechanical circulatory support for RV failure

A new flow path: eDNA connecting hydrology and biology

Environmental DNA (eDNA) has revolutionized ecological research, particularly for biodiversity assessment in various environments, most notably aquatic media. Environmental DNA analysis allows for non-invasive and rapid species detection across multiple taxonomic groups within a single sample, making it especially useful for identifying rare or invasive species. Due to dynamic hydrological processes, eDNA samples from running waters may represent biodiversity from broad contributing areas, which is convenient from a biomonitoring perspective but also challenging, as hydrological knowledge is required for meaningful biological interpretation. Hydrologists could also benefit from eDNA to address unsolved questions, particularly concerning water movement through catchments. While naturally occurring abiotic tracers have advanced our understanding of water age distribution in catchments, for example, current geochemical tracers cannot fully elucidate the timing and flow paths of water through landscapes. Conversely, biological tracers, owing to their immense diversity and interactions with the environment, could offer more detailed information on the sources and flow paths of water to the stream. The informational capacity of eDNA as a tracer, however, is determined by the ability to interpret the complex biological heterogeneity at a study site, which arguably requires both biological and hydrological expertise. As eDNA data has become increasingly available as part of biomonitoring campaigns, we argue that accompanying eDNA surveys with hydrological observations could enhance our understanding of both biological and hydrological processes; we identify opportunities, challenges, and needs for further interdisciplinary collaboration; and we highlight eDNA's potential as a bridge between hydrology and biology, which could foster both domains