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Breakthrough involving novel indole-1,Only two,4-triazole derivatives while tubulin polymerization inhibitors.
Infectious ocular keratitis is the leading cause of blindness worldwide. Bacterial resistance to classical pharmacological treatments raised the interest of researchers towards antimicrobial peptide (AMP)-based therapy. hLF 1-11, a synthetic antimicrobial peptide derived from the N-terminus of human lactoferrin, proved effective against different bacteria and yeast but, like all proteinaceous materials, it is unstable from chemical, physical, and biological points of view. In this study, new freeze-dried solid matrices containing mucoadhesive polymers were prepared and characterized in terms of rheology, hydration time, bioadhesion, drug content, and in vitro release. The formulation HPMC/T2/HA/hLF 1-11fd was selected for the delivery of hLF 1-11, since it showed good drug recovery and no chemical degradation up to at least 6 months (long-term stability). Furthermore, the HPMC/T2/HA/hLF 1-11fd matrix allowed for the release of the drug in a simulated physiological environment, linked to an optimal hydration time, and the peptide antimicrobial activity was preserved for up to 15 months of storage, a very promising result considering the chemical liability of proteinaceous material. For its properties, the freeze-dried matrix developed in this study could be a good platform for the delivery of antimicrobial peptides in the precorneal area to treat infectious phenomena of the ocular surface.Iron overload is related to leukemia transformation in myelodysplastic syndrome (MDS) patients. Siderophores help to transport iron. Type 2-hydroxybutyrate dehydrogenase (BDH2) is a rate-limiting factor in the biogenesis of siderophores. click here Using qRT-PCR, we analyze BDH2mRNA expression in the bone marrow (BM) of 187 MDS patients, 119 de novo acute myeloid leukemia (AML) patients, and 43 lymphoma patients with normal BM. Elevated BDH2mRNA expression in BM is observed in MDS patients (n = 187 vs. 43, normal BM; P = 0.009), and this is related to ferritin levels. Patients with higher BDH2 expression show a greater risk of leukemia progression (15.25% vs. 3.77%, lower expression; P = 0.017) and shorter leukemia-free-survival (medium LFS, 9 years vs. 7 years; P = 0.024), as do patients with a ferritin level ≥350 ng/mL. Additionally, we investigate the mechanisms related to the prognostic ability of BDH2 by using BDH2-KD THP1. The cell cycle analysis, surface markers, and special stain studies indicate that BDH2-KD induces differentiation and decreases the growth rate of THP1 cells, which is associated with the retardation of the cell cycle. Moreover, many genes, including genes related to mitochondrial catabolism, oncogenes, tumor suppressor genes, and genes related to cell differentiation and proliferation influence BDH2-KD THP1 cells. Herein, we demonstrate that BDH2 is involved in cell cycle arrest and the inhibition of differentiation in malignant cells. Furthermore, the high BDH2 expression in MDS patients could be suggestive of a poor prognostic factor. This study provides a foundation for further research on the roles of BDH2 and iron metabolism in the pathogenesis of MDS.Corrosion of taper connections in total hip arthroplasty remains of concern, as particles and ions generated by corrosive processes can cause clinical problems such as periprosthetic osteolysis or adverse reaction to metallic debris. Mechanical surface treatments that introduce compressive residual stresses (RSs) in metallic materials can lead to a better performance in terms of fretting and fatigue and may lower the susceptibility to corrosion. The study investigates the impact of mechanical surface treatments on the corrosion behavior of metallic biomaterials. Compressive RSs were introduced by deep rolling and microblasting in Ti6Al4V and CoCrMo samples. Polished samples served as reference. Corrosion behavior was characterized by repeated anodic polarization. Residual stresses of up to about -900 MPa were introduced by deep rolling with a reach in depth of approximately 500 µm. Microblasting led to compressive RSs up to approximately -800 and -600 MPa for Ti6Al4V and CoCrMo, respectively, in the immediate vicinity of the surface. For Ti6Al4V, microblasting resulted in decreased corrosion resistance with lower breakdown potentials and/or increased passive current densities in comparison to the polished and deep-rolled samples. The corrosion behavior of CoCrMo on the other hand was not affected by the mechanical surface treatments.This study examined associations of home food availabilities with prediabetes and diabetes among 8929 adults (20-70 years) participating in 2007-2010 National Health and Nutrition Examination Surveys. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. Relative to non-diabetic participants (individuals without diabetes or prediabetes), prediabetes participants were associated with lower availabilities of green vegetables (OR = 0.82; 95% CI = 0.73-0.91; p = 0.0006) and fat-free/low-fat milk (OR = 0.80, 95% CI = 0.65-0.89; p = 0.001) and higher sugary drink availability (OR = 1.24, 95% CI = 1.04-1.48; p = 0.02), adjusting for age, sex, and ethnicity (Model 1). The associations remained significant for vegetables (p = 0.005) and fat-free/low-fat milk (p = 0.02) adjusting for additional confounders (body mass index, education, Model 2). Adjusting for dietary components did not change the above results (in model 2) significantly. Participants with high healthy food availability scores had approximately 31% reduction (p = 0.003) in odds of prediabetes compared to those with low scores in Model 1. No associations were detected for diabetes except for fat-free/low-fat milk availability, for which an inverse association was observed in Model 1 (OR = 0.80, 95% CI = 0.65-0.99; p = 0.04). The results show prediabetes participants had lower availability of healthy foods and higher availability of unhealthy foods, suggesting the need to improve healthy food availability at home for this population.Electrooculography (EOG) signals have been widely used in Human-Computer Interfaces (HCI). The HCI systems proposed in the literature make use of self-designed or closed environments, which restrict the number of potential users and applications. Here, we present a system for classifying four directions of eye movements employing EOG signals. The system is based on open source ecosystems, the Raspberry Pi single-board computer, the OpenBCI biosignal acquisition device, and an open-source python library. The designed system provides a cheap, compact, and easy to carry system that can be replicated or modified. We used Maximum, Minimum, and Median trial values as features to create a Support Vector Machine (SVM) classifier. A mean of 90% accuracy was obtained from 7 out of 10 subjects for online classification of Up, Down, Left, and Right movements. This classification system can be used as an input for an HCI, i.e., for assisted communication in paralyzed people.
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