Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals

JC virus (JCV) infection is regularly asymptomatic in healthy individuals. In contrast, in immunocompromised individuals, highly activated virus replication may lead to PML. Peripheral blood cells (PBCs) are found to habor JCV DNA in healthy and diseased individuals and it is discussed that they might be responsible for dissemination of the virus to the central nervous system (CNS) during persistence. To better understand the role of JCV DNA in PBCs for persistent infection and pathogenesis, the authors characterized the extent of JCV infection in Ficoll-gradient purified blood cells (peripheral blood mononuclear cells [PBMCs]) of healthy and human immunodeficiency virus type 1 (HIV-1)-infected individuals. Virus activation in PBMCs from healthy JCV-infected individuals was found at a rate of 0% to 38% at low polymerase chain reaction (PCR) sensitivity. In progressive multifocal leukoencephalopathy (PML) patients, a stronger signal was found, indicating increased virus activation. JCV DNA was regularly detected in T and B lymphocytes and in monocytes at low levels. However, granulocytes were shown to be the predominant reservoir of JCV DNA harboring high copy numbers. Although the overall distribution of viral genomes holds true for the population studied, in the individual, a markedly changed pattern of distribution can be found.     

B-cell activation and allosensitization after left ventricular assist device implantation is due to T-cell activation and CD40 ligand expression

Left ventricular assist device (LVAD) implantation is frequently complicated by B-cell activation and allosensitization, posing a significant risk to successful transplant outcome. This study investigated whether B-cell hyperreactivity and alloantibody production in LVAD recipients involves T-cell dependent pathways. T-cell calcium flux and nuclear translocation of NFATc were used to determine states of T-cell activation. Flow cytometry was used to assess human T- and B-cell activation after culture with LVAD-derived biomaterial particles. Sera from LVAD recipients and controls were tested for the presence of anti-HLA antibodies, and for soluble CD40 ligand. LVAD-derived biomaterial induced rapid and sustained calcium flux into normal T cells, resulting in calcineurin-dependent nuclear translocation of NFATc. This resulted in increased T-cell expression of CD40 ligand and subsequent B-cell activation, which was reduced by inhibitors of T-cell activation (CsA or anti-CD25 mAb) or by anti-CD40 ligand mAb. LVAD recipients demonstrated higher frequencies of anti-HLA antibodies and serum levels of soluble CD40 ligand compared with heart failure controls. The results indicate that exposure of human mononuclear cells to LVAD-derived biomaterial leads to T-cell dependent B-cell activation via CD40--CD40 ligand interaction, and suggest that treatment with calcineurin inhibitors or monoclonal antibodies against either CD25 or CD40 ligand could be effective at preventing B-cell hyperreactivity and allosensitization after LVAD implantation.     

Salecan-Clay Based Polymer Nanocomposites for Chemotherapeutic Drug Delivery Systems; Characterization and In Vitro Biocompatibility Studies

Salecan is a microbial polysaccharide suitable to obtain hydrogel for biomedical applications due to the excellent hydrophilicity and biocompatibility properties. In this work, Salecan of different concentrations was introduced into polymethacrylic acid (PMAA) in the presence of clay to form novel semi synthetic hydrogel nanocomposites systems and loaded afterwards with doxorubicin (DOX). The physical–chemical characteristics of the nanocomposites systems and their effect on the viability, and morphology of MDBK (Madin–Darby bovine kidney), HT-29 human colorectal adenocarcinoma and Colo 205 human colon adenocarcinoma cell lines were investigated. DOX release from the nanocomposite systems, cell up-take and subsequent effect on cell proliferation was also analyzed. It was found that Salecan concentration determined the swelling behavior, structural parameters and morphological features of the nanocomposite systems. The hydrogen bonds strongly influenced the formation of PMAA–Salecan–clay systems, each component bringing its own contribution, thus demonstrating the achievement of an advanced crosslinked network and a more compacted hydrogel nanocomposite morphology. All the synthesized nanocomposites had negligible toxicity to normal MDBK cells and chemoresistent HT-29 cell line, whereas in the case of Colo 205 cells a decrease by 40% of the cell viability was obtained for the sample containing the highest amount of Salecan. This effect was correlated with the lowest pore size distribution leading to highest available specific surface area and entrapped amount of DOX which was further released from the nanocomposite sample. Corroborating all the data it can be suggested that the synthesized nanocomposites with Salecan and clay could be good candidates as vehicles for chemotherapeutic agents.     

Securing sustainable funding for viral hepatitis elimination plans

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct‐acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries’ health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro‐elimination approach in specific populations is less complex and less costly than country‐wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO.     

The Influence of Abrasive and Acidic Aggressions on the Surface Condition of Flowable Composite Resin

The aim of this in vitro study was to evaluate the effect of hydrochloric acid associated with the abrasive effect of toothbrushing on the surface condition of three flowable composite resins used for direct restoration. Seventy samples of each composite resin: Grandio Flow (VOCO, Germany)—group A, Filtek Ultimate Flow (3M-ESPE, MN, USA)—group B, G-aenial Flo X (GC Europe)—group C were prepared, submersed in hydrochloric acid 30% for 60 min and then submitted to simulated toothbrushing procedure using 5000 cycles with toothbrushes with medium and hard bristles, immediately after the chemical attack, after 30 min or without any chemical attack. The sample’s surface roughness was analyzed using a noncontact profilometer (Dektak XT, Bruker, USA). ANOVA and post hoc Bonferroni tests, with a p < 0.05, were used to analyze the values. Hydrochloric acid action for 60 min and six months of toothbrushing using toothbrushes having medium hardness or firm bristles affects the surface roughness of tested flowable composite resins. Toothbrushing with firm bristles immediately after acidic challenge determines increased surface roughness for two of the three flowable composite resins (Grandio Flow and Filtek Ultimate Flow). Toothbrushing with medium or firm bristles thirty minutes after the acidic aggression determine no effect on surface condition of flowable composite resins.     

Anti-human leukocyte antigen antibodies are associated with restenosis after percutaneous coronary intervention for cardiac allograft vasculopathy

BACKGROUND: Percutaneous coronary intervention (PCI) to palliate cardiac allograft vasculopathy (CAV) has been associated with high restenosis rates, possibly related to increased inflammation associated with this disease. Whether markers of immunologic rejection are associated with restenosis in this population is unknown. The goal of the study was to determine the predictors of restenosis after PCI for CAV. METHODS: Records were reviewed retrospectively from a single, high-volume cardiac transplant center. Clinical, angiographic, and immunologic data were collected on all patients postorthotopic heart transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater than 50% stenosis at the previous intervention site. RESULTS: PCI was successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/-3.9 years after OHT. Angiographic follow-up data was available for 79%, with an average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64% for balloon percutaneous transluminal coronary angioplasty and 33% for coronary stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody to major histocompatibility complex (MHC) class I antigen was highly associated with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis severity and smaller target vessel diameter were also predictors of restenosis as in the nontransplant population. CONCLUSIONS: The findings suggest that in patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and that IgG antibodies to MHC class I antigen may help predict the risk of restenosis after PCI in this population.