Quantification of antithrombin isoform proportions in plasma samples of healthy subjects, sepsis patients, and in antithrombin concentrates

Antithrombin (AT) circulates in plasma in two isoforms, AT-alpha (90-95%) and AT-beta (5-10%). AT isoform proportions were measured in plasma samples of 17 healthy subjects and 26 posttraumatic or postoperative septic patients, as well as in 4 commercially available AT concentrates. Total AT was immune-purified from plasma and concentrates. Micellar electrokinetic chromatography was used to analytically separate and quantify the isoforms. Compared with plasma samples of healthy donors, septic plasmas revealed significantly reduced AT activity (p < 0.001) and beta-isoform content (p < 0.05). AT-beta correlated inversely with urea and creatinine serum concentrations (p < 0.01), indicating a relationship between better renal function and higher beta-isoform content. beta-Isoform neither correlated with age, gender, and 28-day mortality, nor with plasma concentrations of various inflammatory and organ function parameters. The commercial AT concentrate, which is equivalent to the current WHO standard, had an AT-beta content close to that found in plasma of healthy subjects. The availability of this novel quantitative AT isoform assay allows, for the first time, a closer look at the role of AT isoforms in hemostasis and sepsis pathophysiology. Copyright (C) 2002 S. Karger AG, Basel

Ashing of photoresists using dielectric barrier discharge cryoplasmas

Plasma ashing of photoresists is a critical step in advanced microelectronics manufacturing as it often leads to extensive damage in porous organosilicate low - κ dielectrics and hinders the use of highly porous films in interconnects. To reduce plasma damage, the authors investigated the feasibility of ashing a 248-nm photoresist with cryoplasma. The authors ashed photoresist-coated silicon wafers with dielectric barrier discharge microplasma generated at temperatures of 170-291 K, a pressure of 100 Torr, applied voltages of V appl = 0.8 - 1.6 kV, and a frequency of f = 20 kHz in both Ar / O 2 and Ar / O2/ N 2 gas mixtures. While the ashing rates at 170 K in Ar / O2 decreased to about 20% of the ashing rates achieved at room temperature and 240 K, the addition of N 2 to the plasma gas enhanced the ashing rates by a factor of 1.5-2. Optical emission spectroscopy measurements of the plasmas showed that, in the Ar / O2 / N 2 mixture, the main reactive species are N 2 radicals; x-ray photoelectron spectra of the ashed photoresists indicated that ashing is initiated from oxygen-containing functional groups of the photoresist. This study showed that decreased ashing rates at low plasma gas temperatures can be significantly enhanced by adjusting the plasma chemistry and that cryoplasma offers a viable process to minimize the damage from ashing of low - κ dielectric materials in interconnects, which will allow nanoelectronic devices to fully benefit from the introduction of such porous materials. © 2013 American Vacuum Society

Human iPSC-Derived Neural Crest Stem Cells Exhibit Low Immunogenicity

Recent clinical trials are evaluating induced pluripotent stem cells (iPSCs) as a cellular therapy in the field of regenerative medicine. The widespread clinical utility of iPSCs is expected to be realized using allogeneic cells that have undergone thorough safety evaluations, including assessment of their immunogenicity. IPSC-derived neural crest stem cells (NCSCs) have significant potential in regenerative medicine; however, their application in cellular therapy has not been widely studied to date, and no reports on their potential immunogenicity have been published so far. In this study, we have assessed the expression of immune-related antigens in iPSC-NCSCs, including human leukocyte antigen (HLA) class I and II and co-stimulatory molecules. To investigate functional immunogenicity, we used iPSC-NCSCs as stimulator cells in a one-way mixed lymphocyte reaction. In these experiments, iPSC-NCSCs did not stimulate detectable proliferation of CD3+ and CD3+CD8+ T cells or induce cytokine production. We show that this was not a result of any immunosuppressive features of iPSC-NCSCs, but rather more consistent with their non-immunogenic molecular phenotype. These results are encouraging for the potential future use of iPSC-NCSCs as a cellular therapy

A Paradigm of Translational Medicine

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a ‘two-way road’ – from bench to bedside and backwards from bedside to bench

Magnetic and Structural Studies of the Quasi-Two-Dimensional Spin-Gap System (CuCl)LaNb2O7

We report magnetization, nuclear magnetic resonance (NMR), nuclear quadrupole resonance (NQR), and transmission electron microscopy (TEM) studies on the quasi-two-dimensional spin-gap system (CuCl)LaNb2O7, a possible candidate for the J1-J2 model on a square lattice. A sharp single NQR line is observed at the Cu and Cl sites, indicating that both Cu and Cl atoms occupy a unique site. However, the electric field gradient tensors at the Cu, Cl, and La sites do not have axial symmetry. This is incompatible with the reported crystal structure. Thus the J1-J2 model has to be modified. We propose alternative two-dimensional dimer models based on the NMR, NQR, and TEM results. The value of the hyperfine coupling constant at the Cu sites indicates that the spin density is mainly on the d(3z2-r2) orbital (z parallel c). At 1.5 K, Cu- and Nb-NMR signals disappear above the critical field Bc1 = 10.3 T determined from the onset of the magnetization, indicating a field-induced magnetic phase transition at Bc1.Comment: 9 pages, 16 figure

A randomised control trial protocol of MuST for vascular access cannulation in hemodialysis patients (MuST Study): contributions for a safe nursing intervention

Background: The vascular access preservation and the maintenance of a complication-free fistula remains an Achilles’heel of hemodialysis in chronic kidney patients due to its substantial contribution to the morbidity and mortality. Systematic studies in the area of examining cannulation practices, achieving complication-free cannulation, and strategies to improve fistula survival are needed. For this reason, we consider it essential to create and investigate new methodologies for approaching fistula in patients on regular HD. The Multiple Single Cannulation Technique (MuST) is based on the association between the rope-ladder (RL) using the arteriovenous vessel through progressive rotation, and the buttonhole (BH) since there are three specific cannulation sites for each cannulation day during the week. The MuST is simple to implement and seems to be a very promising technique in terms of patient safety. Previous studies already showed an arteriovenous fistula survival similar to RL but significantly higher than BH. Methods: This MuST study is a multicenter, prospective, non-blind, parallel-group, randomized controlled trial with the intervention group submitted to MuST and a control group undergoing the rope-ladder, up to 100 subjects for each group. Patients will be randomized 1:1 to one of two cannulation technique (CT), and the follow-up period of this study will be 12 months. Primary outcome is to evaluate the arteriovenous fistula survival rate at 12 months determined by the percentage of fistulas in use from the beginning of the study to the date of the first clinical intervention by angioplasty or vascular surgery, to maintain or restore patency (unassisted patency). Secondary outcome is to evaluate arteriovenous fistula survival rate at 12 month determined by the percentage of fistulas in use from the study start to the date of access abandonment due to dysfunction, patient abandonment, or death, treatment change modality or study end. We will also evaluate the assisted primary patency and include the following secondary outcomes associated with the cannulation technique: Infection, Hematoma, Aneurysm development, and pain. Discussion: The study will investigate whether fistula survival can be improved when using cannulation by MuST compared to the RL. MuST study will provide important information on fistula survival when cannulated by MuST but also information related to its use in fistulas previously cannulated by other CTs.info:eu-repo/semantics/publishedVersio

P16-48. Immunologic and virologic characterization of an ART-treated HIV-1 patients cohort with long-term control of viremia

Background Long-term treatment of primary HIV-1 infection (PHI) may allow the immune reconstitution of responses lost during the acute viremic phase and decrease of peripheral reservoirs. This in turn may represent the best setting for the use of therapeutic vaccines in order to lower the viral set-point or control of viral rebound upon ART discontinuation. Methods We investigated a cohort of 16 patients who started ART at PHI, with treatment duration of ≥4 years and persistent aviremia (&lt;50 HIV-1 copies/ml). The cohort was characterized in terms of viral subtype, cell-associated RNA, proviral DNA and HLA genotype. Secretion of IFN-γ, IL-2 and TNF-α by CD8 T-cells was analysed by polychromatic flowcytometry using a panel of 192 HIV-1-derived epitopes. Results This cohort is highly homogenous in terms of viral subtype: 81% clade B. We identified 44 epitope-specific responses: all patients had detectable responses to &gt;1 epitope and the mean number of responding epitopes per patient was 3. The mean frequency of cytokines-secreting CD8 T-cells was 0.32%. CD8 T-cells secreting simultaneously IFN-γ, IL-2 and TNF-α made up for about 40% of the response and cells secreting at least 2 cytokines for about 80%, consistent with a highly polyfunctional CD8 T-cell profile. There was no difference in term of polyfunctionality when HLA restriction, or recognized viral regions and epitopes were considered. Proviral DNA was detectable in all patients but at low levels (mean = 108 copies/1 million PBMCs) while cell-associated mRNA was not detectable in 19% of patients (mean = 11 copies/1 million PBMCs when detectable). Conclusion Patients with sustained virological suppression after initiation of ART at PHI show polyfunctional CD8 T-cell and low levels of proviral DNA with an absence of residual replication in a substantial percentage of patients. The use of therapeutic vaccines in this population may promote low level of rebound viremia or control of viral replication upon ART cessation