Azathioprine favourably influences the course of malaria

<p>Abstract</p> <p>Background</p> <p>Azathioprine triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Eryptosis may accelerate the clearance of <it>Plasmodium</it>-infected erythrocytes. The present study thus explored whether azathioprine influences eryptosis of <it>Plasmodium</it>-infected erythrocytes, development of parasitaemia and thus the course of malaria.</p> <p>Methods</p> <p>Human erythrocytes were infected <it>in vitro </it>with <it>Plasmodium falciparum (P. falciparum) </it>(strain BinH) in the absence and presence of azathioprine (0.001 – 10 μM), parasitaemia determined utilizing Syto16, phosphatidylserine exposure estimated from annexin V-binding and cell volume from forward scatter in FACS analysis. Mice were infected with <it>Plasmodium berghei (P. berghei) </it>ANKA by injecting parasitized murine erythrocytes (1 × 10⁶) intraperitoneally. Where indicated azathioprine (5 mg/kg b.w.) was administered subcutaneously from the eighth day of infection.</p> <p>Results</p> <p><it>In vitro </it>infection of human erythrocytes with <it>P. falciparum </it>increased annexin V-binding and initially decreased forward scatter, effects significantly augmented by azathioprine. At higher concentrations azathioprine significantly decreased intraerythrocytic DNA/RNA content (≥ 1 μM) and <it>in vitro </it>parasitaemia (≥ 1 μM). Administration of azathioprine significantly decreased the parasitaemia of circulating erythrocytes and increased the survival of <it>P. berghei</it>-infected mice (from 0% to 77% 22 days after infection).</p> <p>Conclusion</p> <p>Azathioprine inhibits intraerythrocytic growth of <it>P. falciparum</it>, enhances suicidal death of infected erythrocytes, decreases parasitaemia and fosters host survival during malaria.</p

Antibacterial effect of a fluoride-containing ZnO/CuO nanocomposite

© 2019 Elsevier B.V. Dental materials that are antimicrobial and acid-resistant can inhibit bacterial colonization and demineralization, thereby preventing caries. Zinc and copper are well-known for their antibacterial effect, as is nanostructured ZnO–CuO composite. Minerals such as fluorine and calcium, can remineralize and demineralize teeth. Therefore, we developed novel fluoride-containing ZnO–CuO (ZCF) nanocomposites; to the best of our knowledge, these are the first nanocomposites of this kind. The fluoride concentrations and antibacterial effects of the ZCF nanocomposites were evaluated. Nanocomposites comprising zinc and copper (ZC), and zinc, copper, and fluorine (ZCF), were prepared by a simple one-step homogeneous coprecipitation method at a low temperature (80 °C), without the use of organic solvent or surfactant. The structure and composition of the ZC and ZCF nanocomposites were examined by scanning electron microscopy–energy-dispersive spectroscopy (SEM-EDS). Quantitative analysis of the mass concentration was performed by using ZAF correction methods. The fluorine content in nanocomposites was evaluated by using proton-induced gamma emission (PIGE) at the Takasaki Advanced Radiation Research Institute in Japan. By using 96-well microtiter plates, we analyzed the antibiotic susceptibility of ZC, ZCF, and the control buffer (phosphate-buffered saline) with Streptococcus mutans (ATCC 25175). The SEM images showed that ZC and ZCF nanocomposites were composed of 3D flower-like microstructures with diameters of approximately 1 μm. Environmental SEM-EDS analysis revealed that ZC contained 43.2% Cu, 55.1% Zn, 2.2% F, and 0.1% Cl, whereas ZCF contained 47.5% Cu, 40.5% Zn, 6.7% F, and 5.9% Cl. Analysis by PIGE showed that ZCF nanocomposite contained 2553.6 ± 199.2 ppm fluorine, whereas no fluoride was detected in ZC. The control buffer enabled bacterial growth to 4 × 107 ± 9 × 106 CFU/mL, whereas ZC allowed growth of 12 ± 8 CFU/mL, and ZCF showed no bacterial growth. Thus, we developed novel fluoride-containing ZnO–CuO nanocomposites, which exhibited antibacterial effects and have the potential for remineralization, thereby demonstrating their potential as multifunctional dental materials

Predicting Cochlear Implant Electrode Placement Using Monopolar, Three-Point and Four-Point Impedance Measurements

Objective: This study aimed to investigate the relationship between cochlear implant (CI) electrode distances to the cochleas inner wall (the modiolus) and electrical impedance measurements made at the CIs electrode contacts. We introduced a protocol for three-point impedances in which we recorded bipolar impedances in response to monopolar stimulation at a neighboring electrode. We aimed to assess the usability of three-point impedances and two existing CI impedance measurement methods (monopolar and four-point impedances) for predicting electrode positioning during CI insertion. Methods: Impedances were recorded during stepwise CI electrode array insertions in cadaveric human temporal bones. The positioning of the electrodes with respect to the modiolus was assessed at each step using cone beam computed tomography. Linear mixed regression analysis was performed to assess the relationship between the impedances and electrode-modiolar distances. The experimental results were compared to clinical impedance data and to an existing lumped-element model of an implanted CI. Results: Three-point and four-point impedances strongly correlated with electrode-modiolar distance. In contrast, monopolar impedances were only minimally affected by changes in electrode positioning with respect to the modiolus. An overall model specificity of 62% was achieved when incorporating all impedance parameters. This specificity could be increased beyond 73% when prior expectations of electrode positioning were incorporated in the model. Conclusion: Three-point and four-point impedances are promising measures to predict electrode-modiolar distance in real-time during CI insertion. Significance: This work shows how electrical impedance measurements can be used to predict the CIs electrode positioning in a biologically realistic model

Associations of Genetic Ancestry with Terminal Duct Lobular Unit Involution among Healthy Women

Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer. Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined the association between genetic ancestry and TDLU involution in normal breast tissue donated by 2014 healthy women in the United States. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR](trend) = 1.36, 95% confidence interval [CI] = 1.07 to 1.74), acini counts per TDLU (OR = 1.47, 95% CI = 1.06 to 2.03), and median TDLU span (OR(trend) = 1.44, 95% CI = 1.08 to 1.91), indicating lower involution, whereas East Asian descendants were associated with decreased TDLU counts (OR(trend) = 0.52, 95% CI = 0.35 to 0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of triple-negative breast cancer in the United States and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk

Introduction

Since the 1990s, Albania has aimed to introduce democratic values into its legislation. This process can come to fruition only by the recognition and protection of private property. As a result, a new Civil Code was enacted at the beginning of the 1990s through intensive collaboration between Albanian and foreign scholars. Book II of the Albanian Civil Code of 1994 highlights the importance of private property. This book fills the gap in the national and international scientific literature since there is no scientific contribution written in English that examines the development of the Albanian law of property showing the similarities and differences between the Albanian and the Italian civil codes. Another novelty rests on its identification of the rules of the Albanian Civil Codes of 1929 and of 1982 that regulate the various legal institutional parts of the property law. Furthermore, this research summarizes the EU impact on Albanian property law by examining the differences between the legal institutions established at the supranational level such as Dir. 2014/60/EU, Dir. 2008/122/EC, Dir. 1346/2000/EC, and Reg. 2015/848 with the current Albanian system. In the conclusions, this research demonstrates that the Albanian law of property of 1994 is similar, sometimes identical, to the rules established in the Italian Civil Code of 1942

DAP12 Signaling Directly Augments Proproliferative Cytokine Stimulation of NK Cells during Viral Infections

Abstract NK cells vigorously proliferate during viral infections. During the course of murine CMV infection, this response becomes dominated by the preferential proliferation of NK cells that express the activation receptor Ly49H. The factors driving such selective NK cell proliferation have not been characterized. In this study, we demonstrate that preferential NK cell proliferation is dependent on DAP12-mediated signaling following the binding of Ly49H to its virally encoded ligand, m157. Ly49H signaling through DAP12 appears to directly augment NK cell sensitivity to low concentrations of proproliferative cytokines such as IL-15. The impact of Ly49H-mediated signaling on NK cell proliferation is masked in the presence of high concentrations of proproliferative cytokines that nonselectively drive all NK cells to proliferate

The DO-KB Knowledgebase: a 20-year journey developing the disease open science ecosystem.

In 2003, the Human Disease Ontology (DO, https://disease-ontology.org/) was established at Northwestern University. In the intervening 20 years, the DO has expanded to become a highly-utilized disease knowledge resource. Serving as the nomenclature and classification standard for human diseases, the DO provides a stable, etiology-based structure integrating mechanistic drivers of human disease. Over the past two decades the DO has grown from a collection of clinical vocabularies, into an expertly curated semantic resource of over 11300 common and rare diseases linking disease concepts through more than 37000 vocabulary cross mappings (v2023-08-08). Here, we introduce the recently launched DO Knowledgebase (DO-KB), which expands the DO\u27s representation of the diseaseome and enhances the findability, accessibility, interoperability and reusability (FAIR) of disease data through a new SPARQL service and new Faceted Search Interface. The DO-KB is an integrated data system, built upon the DO\u27s semantic disease knowledge backbone, with resources that expose and connect the DO\u27s semantic knowledge with disease-related data across Open Linked Data resources. This update includes descriptions of efforts to assess the DO\u27s global impact and improvements to data quality and content, with emphasis on changes in the last two years