Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients.

Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m2 continuous IV infusion for 5 days. Forty-four patients (median age 76 years) were enrolled, and CR/CRi was achieved by 26 patients (59% of all patients, 66.7% of evaluable patients). Fourteen of 21 (66.7%) patients with adverse cytogenetics achieved CR including six out of seven evaluable patients with TP53 mutations. The 4- and 8-week mortality rates were 2.3% and 9.1%, respectively, with median OS of 10.7 months. These results suggest epigenetic priming with decitabine followed by cytarabine should be considered as an option for first-line therapy in older patients with AML. This trial was registered at www.clinicaltrials.gov as # NCT01829503.

Neuroglia targeting nano-therapeutic approaches to rescue aging and neurodegenerating brain.

Despite intense efforts at the bench, the development of successful brain-targeting therapeutics to relieve malicious neural diseases remains primitive. The brain, being a beautifully intricate organ, consists of heterogeneous arrays of neuronal and glial cells. Primarily acting as the support system for neuronal functioning and maturation, glial cells have been observed to be engaged more apparently in the progression and worsening of various neural pathologies. The diseased state is often related to metabolic alterations in glial cells, thereby modulating their physiological homeostasis in conjunction with neuronal dysfunction. A plethora of data indicates the effect of oxidative stress, protein aggregation, and DNA damage in neuroglia impairments. Still, a deeper insight is needed to gain a conflict-free understanding in this arena. As a consequence, glial cells hold the potential to be identified as promising targets for novel therapeutic approaches aimed at brain protection. In this review, we describe the recent strides taken in the direction of understanding the impact of oxidative stress, protein aggregation, and DNA damage on neuroglia impairment and neuroglia-directed nanotherapeutic approaches to mitigate the burden of various neural disorders.

Comparative Evaluation of the Push-Out Bond Strength of Glass Ionomer Cement, Mineral Trioxide Aggregate, Biodentine, and Endosequence Root Repair Material in Repair of Furcation Perforations: An In Vitro Study.

Introduction: An in vitro comparative analysis was performed to calculate the push-out bond strength of commercially existing root repairing cements like glass ionomer cement (GIC), biodentine, mineral trioxide aggregate (MTA), and endosequence root repair material (RRM) employed in furcation perforation, with or without blood contamination present. Materials and Methods: Eighty molars were selected and subjected to furcal perforations. They were categorized based on the cement used for repair (GIC, MTA, biodentine, and endosequence RRM); furthermore, they were sub-divided into two sub-groups, that is, blood contaminated and non-contaminated. For 24 hours, all the samples were kept in an incubator till the materials were fully set. Then these samples were examined for push-out bond strength measurement. Results: The 24-hour push-out bond strength of was the highest in biodentine and the lowest in glass ionomer cement. The push-out bond strength of endosequence RRM, MTA, and GIC was influenced by blood contamination. Conclusion: The push-out bond strength of biodentine was the highest as compared to endosequence RRM, MTA angelus, and GIC. The push-out bond strength of endosequence RRM and MTA angelus after 24 hours with or without blood contamination showed insignificant differences. Group 1A (GIC contaminated with blood) displayed the least push-out bond strength among other groups.

Evaluation of Dissolution of Pulp by Sodium Hypochlorite when Mixed with Tetrasodic Etidronate and Disodic Ethylenediamine Tetraacetate under Controlled Flow.

Background: Sodium hypochlorite serves as the most efficient root canal irrigating fluid. Objectives: This study's goal was to assess the replenished NaOCl's capacity to dissolve the tissue of pulp when combined with 9% tetrasodic etidronate (Na4HEBP), 18% tetrasodic etidronate (Na4HEBP), and 17% disodic ethylenediaminetetraacetate (Na2EDTA) under continuous controlled administration. Materials and Methods: Hundred and twenty complete undamaged teeth of the anterior mandible extracted due to periodontal problems within forty-eight hours were taken as a source of the pulp tissue. Results: It was found that there was a decrease in the weight of pulp tissue in all groups except negative control. Conclusion: NaOCl's potential to dissolve tissue with chelating agents like EDTA and HEBP inside the root canal was unaffected when there was controlled administration of EDTA and HEBP.

Comparison of Different Endodontic Access Cavity Designs on the Fracture Resistance of Tooth in WaveOne Gold and TruNatomy Instrumentation.

Background: An important aspect of the preparation of the access cavity and biomechanical preparation of the root canal is to safeguard as much of the tooth's framework as possible without affecting access and visibility. Objectives: To compare the impact of the conservative design of access preparation and traditional design of access preparation in association with TruNatomy endodontic instrumentation and WaveOne Gold endodontic instrumentation on resistance to fracture by the design of a cavity for endodontic access using finite element analysis. Materials and Methods: Micro-CT radiographic images of 16 human first permanent molars of the mandible were included in the study to create representative finite element analysis computational models. Results: A significant reduction in load for failure after endodontic preparation was observed in TDAP subcategories as compared to specimens with CDAP. However, the reduction in load for failure was comparable in both endodontic instrument systems within the CDAP and TDAP. Conclusion: A significant reduction in load for failure after endodontic preparation was observed in the traditional design of access preparation subcategories as compared to specimens with the conventional design of access preparation.