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OBJECTIVES The aim of this study was to assess the in vitro caries preventive effect of nanocomplexed solutions of hydroxypropyl-β-cyclodextrin and γ-cyclodextrin associated with titanium tetrafluoride (TiF4) after different complexation times (12 or 72 h). MATERIALS AND METHODS Enamel blocks were randomly distributed in 9 groups (n = 11) negative control, hydroxypropyl-β-cyclodextrin, γ-cyclodextrin, TiF4, hydroxypropyl-β-cyclodextrinTiF4 12 h, hydroxypropyl-β-cyclodextrinTiF4 72 h, γ-cyclodextrinTiF4 12 h, γ-cyclodextrinTiF4 72 h, and NaF (positive control). The solutions were applied for 1 min and the blocks were exposed to a biofilm model. Nanocompounds were characterized by differential scanning calorimetry and X-ray powder diffraction. The percentage of surface microhardness loss (%SML), mineral density changes (ΔZ), lesion depth, surface morphology (scanning electron microscopy-SEM), and chemical characterization (energy-dispersive spectroscopy-EDS) were assessed. RESULTS No oxidation was observed, and the formation of the nanocomplexes was evidenced by changes in the melting point compared to pure cyclodextrins and the loss of crystallinity of the materials. Hydroxypropyl-β-cyclodextrinTiF4 72 h resulted in lower %SML than negative control, hydroxypropyl-β-cyclodextrin, γ-cyclodextrin, and TiF4 (p  0.05). Selleckchem Caspase inhibitor SEM/EDS detected Ti in the blocks subjected to TiF4-products. CONCLUSION The hydroxypropyl-β-cyclodextrinTiF4 72 h solution showed caries preventive effect on the surface and subsurface of the enamel. CLINICAL RELEVANCE A hydroxypropyl-β-cyclodextrin nanosystem, in association with TiF4 after 72 h of complexation, may be a promising agent for the prevention of enamel demineralization.A Gram-stain-positive, aerobic, spore-forming actinobacterial strain, designated 160415T, was isolated from a surface soil sample, which was formed on basaltic parent material, collected from Samsun, Turkey. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 160415T clustered closely with species of the genus Nonomuraea, and showed the highest sequence similarity to Nonomuraea zeae NEAU-ND5T, Nonomuraea candida HMC10T and Nonomuraea turkmeniaca DSM 43926T with 99.1%, 98.9% and 98.7%, respectively. Chemotaxonomic properties including major menaquinones, diaminopimelic acid, sugar and phospholipid profiles also confirmed the affiliation of the strain to the genus Nonomuraea. The DNA G+C content of strain 160415T was 69.6 mol%. DNA-DNA hybridization and average nucleotide identity values between the strain and closely related type strains were less than the recommended cut-off values. On the basis of phylogenetic relationships, genotypic and phenotypic characterizations, strain 160415T represents a novel species of the genus Nonomuraea, for which the name Nonomuraea basaltis sp. nov. is proposed. The type strain is 160415T (= KCTC 39875T = DSM 104309T).Time delays play important roles in genetic regulatory networks. In this paper, a gene regulatory network model with time delays and mutual inhibition is considered, where time delays are regarded as bifurcation parameters. In the first part of this paper, we analyze the associated characteristic equations and obtain the conditions for the stability of the system and the existence of Hopf bifurcations in five special cases. Explicit formulas are given to determine the direction and stability of the Hopf bifurcation by using the normal form method and the center manifold theorem. Numerical simulations are then performed to illustrate the results we obtained. In the second part of the paper, using time-delayed stochastic numerical simulations, we study the impact of biological fluctuations on the system and observe that, in modest noise regimes, unexpectedly, noise acts to stabilize the otherwise destabilized oscillatory system.In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF.AIMS In ENSURE-AF (NCT02072434), the oral Factor Xa inhibitor edoxaban showed similar efficacy and safety vs enoxaparin-warfarin in patients undergoing electrical cardioversion of nonvalvular atrial fibrillation (AF). This ancillary analysis compares primary efficacy and safety end points for patients receiving vs not receiving concomitant antiplatelet therapy (APT) in ENSURE-AF. METHODS The primary efficacy end point was a composite of stroke, systemic embolic events, myocardial infarction, and cardiovascular death during 28 days on study drug after cardioversion plus 30 days of follow-up. The primary safety end point was the composite of major and clinically relevant non-major bleeding occurring between the first and the last dose of study drug. RESULTS Of 2199 patients enrolled, 1095 were randomized to edoxaban and 1104 to enoxaparin-warfarin. Patients receiving concomitant APT were older; more naïve to vitamin K antagonist; had lower creatinine clearance; and more likely to have history of coronary artery disease, hypertension, diabetes, or ischemic stroke/transient ischemic attack.

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