Population-based study of diagnostic assays for Borrelia infection: comparison of purified flagella antigen assay (Ideia™, Dako Cytomation) and recombinant antigen assay (Liaison®, DiaSorin)

<p>Abstract</p> <p>Background</p> <p>Testing for <it>Borrelia</it>-specific IgM and IgG-antibodies are often performed on a variety of poorly defined symptoms, and isolated IgM results are a frequent finding, which results in diagnostic uncertainty and further testing. We wanted to test the hypothesis that Borrelia-specific assays using recombinant antigens perform differently from assays based on purified flagella antigen.</p> <p>Methods</p> <p>We compared the use of recombinant antigens (LIAISON^®DiaSorin, Saluggia, Italy) and purified flagella antigen (IDEIA™ Borrelia, DakoCytomation, Glostrup, Denmark) in the assay for <it>Borrelia</it>-specific IgM and IgG-antibodies. The assays were tested on an unselected population of serum samples submitted from general practice. A total of 357 consecutive samples for analysis of <it>Borrelia </it>IgM and IgG antibodies. Furthermore, we analysed 540 samples for <it>Borrelia</it>-specific IgM or IgG antibodies first by the IDEIA™ and, if they were positive, the samples were further analysed using the LIAISON^®assay. To verify the correctness of the patient's serological status, discrepant samples were analysed by line blots (EcoLine, Virotech).</p> <p>Results</p> <p>In the consecutive series of 357 samples, the IgM assays detected 308 negative and 3 positive samples with concordant results. Compared with the line blot, the IDEIA™ system produced 21 false-positive IgM results, whereas the LIAISON^®system produced only one false-positive IgM result. The IgG assays showed 1 positive and 328 negative concordant results. The LIAISON^®system produced 9 true IgG-positive samples that were not detected by the IDEIA™ system, but the former produced 4 positive IgG results that were negative by line blot.</p> <p>Conclusion</p> <p>Diagnostic assays based on flagella antigen seem to show more false-positive IgM and false-negative IgG results than assays based on recombinant antigens. The latter may reduce the number of presumably false-positive IgM results and identify more IgG-positive subjects, but this system also produces more false-positive IgG results.</p

Role of nickel in high rate methanol degradation in anaerobic granular sludge bioreactors

The effect of nickel deprivation from the influent of a mesophilic (30°C) methanol fed upflow anaerobic sludge bed (UASB) reactor was investigated by coupling the reactor performance to the evolution of the Methanosarcina population of the bioreactor sludge. The reactor was operated at pH 7.0 and an organic loading rate (OLR) of 5–15 g COD l−1 day−1 for 191 days. A clear limitation of the specific methanogenic activity (SMA) on methanol due to the absence of nickel was observed after 129 days of bioreactor operation: the SMA of the sludge in medium with the complete trace metal solution except nickel amounted to 1.164 (±0.167) g CH4-COD g VSS−1 day−1 compared to 2.027 (±0.111) g CH4-COD g VSS−1 day−1 in a medium with the complete (including nickel) trace metal solution. The methanol removal efficiency during these 129 days was 99%, no volatile fatty acid (VFA) accumulation was observed and the size of the Methanosarcina population increased compared to the seed sludge. Continuation of the UASB reactor operation with the nickel limited sludge lead to incomplete methanol removal, and thus methanol accumulation in the reactor effluent from day 142 onwards. This methanol accumulation subsequently induced an increase of the acetogenic activity in the UASB reactor on day 160. On day 165, 77% of the methanol fed to the system was converted to acetate and the Methanosarcina population size had substantially decreased. Inclusion of 0.5 μM Ni (dosed as NiCl2) to the influent from day 165 onwards lead to the recovery of the methanol removal efficiency to 99% without VFA accumulation within 2 days of bioreactor operation

Global Protection and the Health Impact of Migration Interception

In the fourth article in a six-part PLoS Medicine series on Migration & Health, Zachary Steel and colleagues discuss the interception phase of migration and the specific health risks and policy needs associated with this phase

Geometric and Electronic Structures of the NiI and Methyl−NiIII Intermediates of Methyl-Coenzyme M Reductase†

ABSTRACT: Methyl-coenzyme M reductase (MCR) catalyzes the terminal step in the formation of biological methane from methyl-coenzyme M (Me-SCoM) and coenzyme B (CoBSH). The active site in MCR contains a Ni-F430 cofactor, which can exist in different oxidation states. The catalytic mechanism of methane formation has remained elusive despite intense spectroscopic and theoretical investigations. On the basis of spectroscopic and crystallographic data, the first step of the mechanism is proposed to involve a nucleophilic attack of the NiI active state (MCRred1) on Me-SCoM to form a NiIII-methyl intermediate, while computational studies indicate that the first step involves the attack of NiI on the sulfur of Me-SCoM, forming a CH3 radical and a NiII-thiolate species. In this study, a combination of Ni K-edge X-ray absorption spectroscopic (XAS) studies and density functional theory (DFT) calculations have been performed on the NiI (MCRred1), NiII (MCRred1-silent), and NiIII-methyl (MCRMe) states of MCR to elucidate the geometric and electronic structures of the different redox states. Ni K-edge EXAFS data are used to reveal a five-coordinate active site with an open upper axial coordination site in MCRred1. Ni K-pre-edge and EXAFS data and time-dependent DFT calculations unambiguously demonstrate the presence of a long Ni-C bond (∼2.04 Å) in the NiIII-methyl state of MCR. The formation and stability of this species support mechanism I, and the Ni-C bond length suggests a homolytic cleavage of the NiIII-methyl bon

Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection

Following productive, lytic infection in epithelia, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons that is interrupted by episodes of reactivation. In order to better understand what triggers this lytic/latent decision in neurons, we set up an organotypic model based on chicken embryonic trigeminal ganglia explants (TGEs) in a double chamber system. Adding HSV-1 to the ganglion compartment (GC) resulted in a productive infection in the explants. By contrast, selective application of the virus to distal axons led to a largely nonproductive infection that was characterized by the poor expression of lytic genes and the presence of high levels of the 2.0-kb major latency-associated transcript (LAT) RNA. Treatment of the explants with the immediate-early (IE) gene transcriptional inducer hexamethylene bisacetamide, and simultaneous co-infection of the GC with HSV-1, herpes simplex virus type 2 (HSV-2) or pseudorabies virus (PrV) helper virus significantly enhanced the ability of HSV-1 to productively infect sensory neurons upon axonal entry. Helper-virus-induced transactivation of HSV-1 IE gene expression in axonally-infected TGEs in the absence of de novo protein synthesis was dependent on the presence of functional tegument protein VP16 in HSV-1 helper virus particles. After the establishment of a LAT-positive silent infection in TGEs, HSV-1 was refractory to transactivation by superinfection of the GC with HSV-1 but not with HSV-2 and PrV helper virus. In conclusion, the site of entry appears to be a critical determinant in the lytic/latent decision in sensory neurons. HSV-1 entry into distal axons results in an insufficient transactivation of IE gene expression and favors the establishment of a nonproductive, silent infection in trigeminal neurons

Irregular Migration Theories

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Hepcidin as a potential predictor for preoperative anemia treatment with intravenous iron-A retrospective pilot study.

Preoperative anemia occurs in about one third of patients who undergo elective surgery and is associated with an impaired outcome. Therefore, screening of preoperative anemia was established in the context of a multidisciplinary Patient Blood Management (PBM) program at the University Hospital of Muenster, Germany. Anemic patients without contraindications were treated with intravenous (IV) iron (ferric carboxymaltose) to increase their hemoglobin (Hgb) levels and hence to treat anemia prior to surgery. Interestingly, we detected a large variability in the response of Hgb levels after IV iron administration. Systemic iron homeostasis is mainly regulated by the hepatic hormone hepcidin, which regulates the cell surface expression of the sole known iron exporter ferroportin. The objective of this retrospective pilot study was to analyze the potential of hepcidin to predict the response of anemic patients to preoperative IV iron treatment measured as increase in Hgb. Serum samples of non-anemic (n = 48), untreated anemic (n = 64) and anemic patients treated with IV iron (n = 79), in total 191 patients, were collected between October 2014 until June 2016. Serum hepcidin levels were determined and data were analyzed retrospectively. The analysis revealed at first a correlation between serum hepcidin levels and the parameters of the iron status. Second, patients treated with IV iron showed a noticeably higher increase in their delta Hgb level between PBM consultation and surgery (0.45g/dl [0.05, 1.05] compared to patients without IV iron (0.1g/dl [-0.48, 0.73], *p = 0.03). Patients were then grouped into 'non-responders', defined as delta Hgb <0.6g/dl and 'responders', with delta Hgb ≥0.6g/dl between the day of IV iron treatment and the day of surgery. Within normal ranges and clinically unapparent, a statistically noticeable difference between responders and non-responders was found for CRP and leukocytes. Serum hepcidin levels were higher in the group of non-responders (10.6ng/ml [3.93, 34.77]) compared to responders (2.1ng/ml [0.25, 7.97], *p = 0.04). To conclude, the data of this retrospective pilot study indicate that hepcidin might be a promising biomarker to predict a patient`s responsiveness to IV iron in preoperative anemia treatment. Prospective studies have to investigate serum hepcidin levels as a biomarker to guide physician`s decision on IV iron substitution

Making media: foundations of sound and image production

<p>Four studies that analyzed hepcidin as a potential biomarker and/or the correlation between hepcidin and ferritin.</p