Bryanfleming4915

Aim We report here the development of tenofovir- and curcumin-loaded lactoferrin nanoparticles (TCNPs) as an HIV-microbicide. Materials & methods TCNPs were subjected to various physicochemical characterization experiments, followed by in vitro and in vivo experiments to assess their efficacy. Results TCNPs had a diameter of 74.31 ± 2.56 nm with a gross encapsulation of more than 61% for each drug. Nanoparticles were effective against HIV-1 replication, with an IC50 of 1.75 μM for curcumin and 2.8 μM for tenofovir. TCNPs provided drug release at the application site for up to 8-12 h, with minimal leakage into the systemic circulation. TCNPs showed spermicidal activity at ≥200 μM and induced minimal cytotoxicity and inflammation in the vaginal epithelium as revealed by histopathological and ELISA studies. Conclusion We demonstrated that TCNPs could serve as a novel anti-HIV microbicidal agent in rats. [Formula see text].Aim We present data on sonodynamic therapy (SDT) against glioblastoma cells utilizing titanium dioxide (TiO2) nanoparticles conjugated to anti-EGFR antibody. Materials & methods TiO2 nanoparticles were bound to anti-EGFR antibody to form antibody-nanoparticle conjugates (ANCs), then characterized by x-ray photoelectron spectroscopy and transmission electron microscopy. Cells underwent ultrasound and assessment on viability, reactive oxygen species and apoptosis were performed. Results X-ray photoelectron spectroscopy analysis revealed the formation of an ANC. Transmission electron microscopy showed internalization of the ANCs by glioblastoma cells. With SDT, cell viabilities were reduced in the presence of ANCs, reactive oxygen species production was formed, but minimal effect on apoptosis was seen. Conclusion For the first time, an ANC can be used with SDT to kill glioblastoma cells.Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.Background Increased high-sensitivity cardiac troponin T (hs-cTnT) above the upper reference limit (URL) after noncardiac surgery identifies patients at risk for mortality. Prior studies have not analyzed hs-cTnT as a continuous variable or probed age- and sex-specific URLs. This study compared the prediction of 30-day mortality using continuous postoperative hs-cTnT levels to the use of the overall URL and age- and sex-specific URLs. Methods and Results Patients (876) >40 years of age who underwent noncardiac surgery were included. Hs-cTnT was measured on postoperative day 1. Cox proportional hazards models were used to compare associations between 30-day mortality and using hs-cTnT as a continuous variable, or above the overall or age- and sex-specific URLs. Comparisons were performed by the area under the receiver operating characteristic curve analysis. Mortality was 4.2%. For each 1 ng/L increase in postoperative hs-cTnT, there was a 0.3% increase in mortality (P14 ng/L were 37% of the cohort, while those above age- and sex-specific URLs were 25.3%. Both manifested higher mortality (hazard ratio [HR], 3.19; 95% CI, 1.20-8.49; P=0.020) and (HR, 2.76; P=0.009) than those with normal levels. The area under receiver operating characteristic curve was 0.89 using hs-cTnT as a continuous variable, 0.87 for age- and sex-specific URLs, and 0.86 for the overall URL. Conclusions Hs-cTnT as a continuous variable was independently associated with 30-day mortality and had the highest accuracy. PB 203580 Hs-cTnT elevations using overall and/or age- and sex-specific URLs were also associated with higher mortality.Background In pursuit of novel mechanisms underlying persistent low medication adherence rates, we assessed contributions of implicit and explicit attitudes, beyond traditional risk factors, in explaining variation in objective and subjective antihypertensive medication adherence. Methods and Results Implicit and explicit attitudes were assessed using the difference scores from the computer-based Single Category Implicit Association Test and the Necessity and Concerns subscales of the Beliefs about Medicines Questionnaire, respectively. Antihypertensive medication adherence was measured using pharmacy refill proportion of days covered (PDC mean PDC, low PDC less then 0.8) and the self-report 4-item Krousel-Wood Medication Adherence Scale (K-Wood-MAS-4 mean K-Wood-MAS-4, low adherence via K-Wood-MAS-4 ≥1). Hierarchical logistic and linear regression models controlled for traditional risk factors including social determinants of health, explicit, and implicit attitudes in a stepwise fashion. Community-dwelling insured participants (n=85 44.