Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.

BACKGROUND: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated. OBJECTIVES: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients. METHODS: We examined plasma levels of activators, inhibitors, and biomarkers of the coagulation and fibrinolytic pathways in patients aged ≥18 years with newly diagnosed acute leukemia compared with those of normal controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and DVT in acute leukemia patients. The study included 358 patients with acute leukemia (29 with acute promyelocytic leukemia [APL], 253 with non-APL acute myeloid leukemia, and 76 with acute lymphoblastic leukemia) and 30 normal controls. RESULTS: Patients with acute leukemia had higher levels of extracellular vesicle tissue factor (EVTF) activity, phosphatidylserine-positive extracellular vesicles, plasminogen activator inhibitor-1, plasmin-antiplasmin complexes, and cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared with normal controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among acute leukemia patients. There were 41 bleeding and 23 DVT events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (subdistribution hazard ratio, 2.30; 95% CI, 0.99-5.31), whereas high levels of plasminogen activator inhibitor-1 were associated with increased risk of DVT (subdistribution hazard ratio, 3.00; 95% CI, 0.95-9.47) in these patients. CONCLUSION: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and DVT.

Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.

Background: Coagulopathy and associated bleeding and venous thromboembolism (VTE) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated. Objectives: To evaluate the associations between biomarker levels and bleeding and VTE in acute leukemia patients. Patients/Method: We examined plasma levels of activators, inhibitors and biomarkers of the coagulation and fibrinolytic pathways in patients ≥18 years with newly diagnosed acute leukemia compared to healthy controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and VTE in acute leukemia patients. The study included 358 patients with acute leukemia (29 acute promyelocytic leukemia [APL], 253 non-APL acute myeloid leukemia [AML] and 76 acute lymphoblastic leukemia [ALL]), and 30 healthy controls. Results: Patients with acute leukemia had higher levels of extracellular vesicle (EV) tissue factor (TF) activity, phosphatidylserine-positive EVs, plasminogen activator inhibitor-1 (PAI-1), plasmin-antiplasmin complexes, cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared to healthy controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among the acute leukemia patients. There were 41 bleeding and 37 VTE events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (sHR 2.30, 95%CI 0.99-5.31) whereas high PAI-1 was associated with increased risk of VTE (sHR 3.79, 95%CI 1.40-10.28) in these patients. Conclusions: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and VTE.

Self-Assembled Nanostructures from Amphiphilic Sucrose-Soyates for Solubilizing Hydrophobic Guest Molecules.

We studied self-assembly and colloidal properties of poly(ethylene glycol) (pEG) conjugated sucrose soyate polyols (PSSP). These molecular platforms were synthesized by covalently connecting PEGs of different molecular weights (Mn) (12 and 16 ethylene oxide units) to epoxidized sucrose soyate (ESS). The synthesized PSSP products showed amphiphilicity, reduced water surface tension, and exhibited critical Aggregation Concentration (CAC) within the range of 0.3-0.4 mg/mL. We observed that PSSP self-assembles in water in the form of nanoparticles without the need of any cosolvents. These nanoparticles exhibited number-average hydrodynamic diameter of 120 ± 8 nm with a polydispersity index (PDI) of <0.3, and negatively charged surfaces. We also found out that PSSP nanoparticles can encapsulate and homogeneously distribute a hydrophobic model compound, such as a phthalocyanine dye, Solvent Blue-70 (BL-70), on a metal surface. Collectively, our studies explored and demonstrated the possibility of molecular diversification of biobased starting materials to form amphiphilic nanoparticles with industrially relevant colloidal and surface properties.

Frontal Polymerization of a Thin Film on a Wood Substrate.

Frontal polymerization has been explored as a technique to form two-dimensional thin films (<0.5 mm) on wood. We used trimethylolpropane triacrylate with a thermal free-radical initiator. The viscosity of the resin was adjusted by incorporating fumed silica within the formulation. As filler materials, either calcium carbonate or graphene nanoplatelets was used to evaluate the effect of filler type and content on front propagation. We observed that resin viscosity and film thickness critically affected the qualitative and quantitative propagation of the thermal front resulting in the formation of the coating. A workable coating was formed at a viscosity of 0.6 Pa·s, which was obtained when 3 phr (parts per hundred resin) of fumed silica was used in the resin formulation. Wet film thickness for this resin system was also found to have a limiting value, and full propagation of the front to result in a conformal coating required at least 15 mil (1 mil = 25 µm) of wet film thickness. Filler materials affected film propagation as a function of particle size and thermal properties. While 15 phr calcium carbonate could be incorporated with the resin, only 5 phr graphene nanoplatelets could be loaded within the matrix to ensure complete propagation of the front. Interestingly, for graphene fronts, velocity and temperature reduced systematically as a function of filler content. Filler type and content affected porosity and roughness of the coating, which was quantified by computerized tomography to understand the relationship between porosity and adhesion of the coated film with the wood substrate.

Effect of Different Finishing and Polishing Systems on the Surface Roughness of Resin Composite and Enamel: An In vitro Profilometric and Scanning Electron Microscopy Study.

AIM: The aim is to compare and evaluate the different finishing and polishing systems for the change in surface roughness of resin composites and enamel. MATERIALS AND METHODS: To conduct the study, 30 extracted human maxillary central incisors were selected, decoronated, and molded in self-cure acrylic molds. A box-shaped cavity of dimensions 3 mm × 3 mm × 2 mm was prepared in all the teeth. A nanohybrid composite resin (Filtek Z250) was then used to restore the prepared cavities. Thirty samples were divided into two groups, control group (Group A, n = 10) and experimental group (Group B, n = 20). The samples in Group A were cured through the Mylar matrix. The experimental group, i.e., Group B was divided into two subgroups, i.e., Subgroup BX, n = 10 in which Sof-Lex polishing system was used for polishing the tooth surface and Subgroup BF, n = 10 in which Shofu composite polishing system was used. The mean surface roughness (Ra in µm) of the composite restoration as well as for the enamel surface of all the samples before and after polishing was measured with a contact profilometer, and the values were correlated with scanning electron microscopy. RESULTS: The statistical analysis was carried out using paired t-test. The results exhibited a significant decrease in the surface roughness of the resin composite and enamel surface irrespective of the finishing and polishing system used. The mean surface roughness values demonstrated by Mylar matrix was the lowest followed by Sof-Lex polishing system. Shofu polishing system demonstrated the highest surface roughness values. CONCLUSION: Finishing and polishing of composite restoration can achieve a surface roughness similar to that of enamel. Involvement of marginal enamel in finishing and polishing procedures carried out for composite restoration results in smoother enamel surface.

Plaque Removal Efficacy of Different Toothbrushes: A Comparative Study.

AIM AND OBJECTIVE: This study aimed to compare the plaque removal efficacy of different toothbrushes and to ascertain the most efficient mechanical mean for daily plaque removal so as to maintain oral health in a preeminent way. STUDY DESIGN: It was a randomized controlled clinical trial consisting of 60 subjects divided into three groups (group I ultrasonic and sonic toothbrush, group II multidirectional toothbrush, and group III manual toothbrush) with 20 in each group. Prebrushing and postbrushing plaque scores were recorded at weekly intervals for four weeks using Turesky modification of Quigley and Hein plaque index. RESULTS: Statistically significant differences (p < 0.001) existed in mean percent reduction of pre-day 1 to pre-day 28 mean percent reduction in plaque values of the ultrasonic toothbrush group (111.92 ± 25.20), the multidirectional toothbrush group (189.06 ± 52.70), and the manual toothbrush group (42.34 ± 14.77). Similar results were found in post-day 1 to post-day 28 mean percent reduction in plaque values. CONCLUSION: Group II (i.e., multidirectional toothbrush) showed maximum mean percent reduction in prebrushing and postbrushing plaque scores at the end of four weeks when compared with the baseline values followed by ultrasonic toothbrush and manual toothbrush. HOW TO CITE THIS ARTICLE: Aggarwal N, Gupta S, Grover R, et al. Plaque Removal Efficacy of Different Toothbrushes: A Comparative Study. Int J Clin Pediatr Dent 2019;12(5):385-390.

Oxygen transfer rates in shaken culture vessels from Fernbach flasks to microtiter plates.

By a sulfite oxidation method, oxygen transfer rates (OTRs) were determined in 11 types of culture vessels from 2.8-L Fernbach (FB) flasks to 96-, 48-, and 24-well square deepwell microtiter plates (MTPs). OTRs ranged from 140 mM/h in 250-mL Ultrayield™ flasks shaken at 300 rpm with a 50 mm diameter shaker throw to 5 mM/h in unbaffled FBs shaken at 200 rpm with a 25 mm throw. Baffles in FBs increased OTRs 6-12-fold under various shaking conditions, and up to five-fold in 250-mL flasks, depending on the type of baffles. Corner-baffling was superior to bottom-baffling in glass, 250-mL flasks. In MTPs, OTRs increased with increasing well size and decreasing fill volume. At 50 mm throw and 300 rpm, 24-well MTPs had OTRs comparable to corner-baffled, 250-mL flasks (∼100 mM/h). The OTRs in unbaffled flasks were relatively insensitive to shaking conditions, increasing less than two-fold between the most modest and the most vigorous conditions. There was no consistency across vessels as to whether the alternate incubation conditions of 70 mm throw and 250 rpm produced higher OTRs than the 50 mm throw and 300 rpm regimen. No increase in OTR was seen in any MTP when the cover hole diameter was increased beyond 4.5 mm. OTRs decreased as viscosity increased, falling smoothly in unbaffled flasks and 24-well MTPs, but 48-well and 96-well MTPs showed precipitous OTR drops as viscosity increased. Matching the OTRs of screening vessels to the oxygen uptake rates of microbial cultures can greatly reduce the number of false positive strains that are forwarded from microbial screens. Biotechnol. Bioeng. 2016;113: 1729-1735. © 2016 Wiley Periodicals, Inc.

A positive feedback-based gene circuit to increase the production of a membrane protein.

BACKGROUND: Membrane proteins are an important class of proteins, playing a key role in many biological processes, and are a promising target in pharmaceutical development. However, membrane proteins are often difficult to produce in large quantities for the purpose of crystallographic or biochemical analyses. RESULTS: In this paper, we demonstrate that synthetic gene circuits designed specifically to overexpress certain genes can be applied to manipulate the expression kinetics of a model membrane protein, cytochrome bd quinol oxidase in E. coli, resulting in increased expression rates. The synthetic circuit involved is an engineered, autoinducer-independent variant of the lux operon activator LuxR from V. fischeri in an autoregulatory, positive feedback configuration. CONCLUSIONS: Our proof-of-concept experiments indicate a statistically significant increase in the rate of production of the bd oxidase membrane protein. Synthetic gene networks provide a feasible solution for the problem of membrane protein production.