scholarly journals Large-scale seroepidemiology identifies a nephro-vascular syndrome associated with autoimmune reactivity to tau

2021 ◽  
Author(s):  
Andreia D. Magalhães ◽  
Marc Emmenegger ◽  
Elena De Cecco ◽  
Manfredi Carta ◽  
Karl Frontzek ◽  
...  
Keyword(s):  
Large Scale ◽  
Potential Role ◽  
University Hospital ◽  
Arterial Embolism ◽  
Urinary Disorders ◽  
Healthy Donors ◽  
Embolism And Thrombosis ◽  
Antibody Titers ◽  
Autoimmune Reactivity

The microtubule-associated protein tau is involved in several neurodegenerative diseases and is currently being investigated as a plasma biomarker for the detection and monitoring of Alzheimer's disease and as an immunotherapeutical target in clinical trials. We assessed plasma anti-tau IgG reactivity in 40'098 unselected patients visiting a university hospital and healthy blood donors. We found that 4.97% patients and 1.58% healthy donors had natural anti-tau antibody titers >1.8 log10(EC50). In a multivariate model, female sex (P<0.001), age (P<0.001), cystitis (RR 1.59, 95%CI 1.14-2.16, P=0.004), other urinary disorders (RR 1.23, 95%CI 1.03-1.45, P=0.018), chronic kidney disease (RR 1.20, 95%CI 1.01-1.41, P=0.033), arterial embolism and thrombosis (RR 1.56, 95%CI 1.02-2.25, P=0.026) and atherosclerosis (RR 1.35, 95%CI 1.09-1.1.66, P=0.004) were independent predictors of anti-tau autoantibodies. We therefore conclude that anti-tau autoimmunity is associated with a systemic syndrome that includes vascular, kidney and urinary disorders. The expression of tau in these extraneural tissues suggests a potential role of autoimmunity in this syndrome.

scholarly journals Body mass index and adipokines/cytokines dysregulation in Systemic Sclerosis

2021 ◽  
Author(s):  
F Iannone ◽  
Emanuela Praino ◽  
Cinzia Rotondo ◽  
Dorotea Natuzzi ◽  
Rita Bizzoca ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Systemic Sclerosis ◽  
Body Mass ◽  
Potential Role ◽  
Serum Levels ◽  
Waist To Hip Ratio ◽  
Healthy Donors ◽  
Underweight Patients ◽  
Regulatory Functions

Body fat has regulatory functions through producing cytokines and adipokines whose role in the pathogenesis of Systemic Sclerosis (SSc) is currently emerging. Changes in body mass, either overweight or underweight status, entail a dysregulation of the cytokines/adipokines network that may impact on SSc disease activity. We evaluated serum levels of adipokines and cytokines in SSc patients and correlated them to clinical features and body mass index (BMI) categories. The study included 89 SSc patients and 26 healthy donors (HD). Serum levels of adiponectin, leptin, resistin, visfatin, TNFα, IFNγ, IL-2, IL-10, and IL-17A were measured by Multiplex Immunoassay, and correlated to BMI, waist to hip ratio, and disease specific features. Mann-Whitney U-test or t-Student for unpaired data, Kruskal-Wallis test or ANOVA, were used for comparisons between groups. Spearman’s or Pearson’s test were used for correlation analysis. Serum levels of TNFα, IL-2, leptin, and resistin, were significantly higher in SSc than in HD. The highest levels of IL-17A, IL-2, IL-10, leptin and visfatin were detected in obese SSc patients (p <0.01). Conversely, underweight SSc patients showed the highest TNFα levels (p<0.05), which were negatively correlated with BMI (p=0.05). No correlation between adipokines/cytokines and clinical characteristics was found. Adipokines, IL-2, IL-10 and IL-17A were found to be increased in obese SSc patients, but whether they play a role in the pathogenesis of the disease remains to be investigated. Intriguingly, underweight patients had higher TNFα levels, suggesting a potential role of TNFα in inducing the cachexia observed in long-lasting disease.

The Predictive Role of Germinal Center or Non-Germinal Center Phenotypes in Diffuse Large B-Cell Lymphoma Patients Receiving CHOP or R-CHOP

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5290-5290
Author(s):  
Sun-ah Lee ◽  
Hun-Mo Ryoo ◽  
Sung Hwa Bae ◽  
Hyun Young Jung ◽  
Saet Byul Jang ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Large Scale ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
University Hospital ◽  
Large B Cell Lymphoma ◽  
Predictive Role ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma. It can be divided into the germinal center (GC) and non-GC subtypes by immunohistochemistry based on the expression of CD10, Bcl-6 and MUM-1. The GC Subtype had a significantly better survival rate than the non-GC subtype. These subtypes are predictors of outcome in DLBCL patients receiving CHOP (cyclophosphamide, adriamycin, vincristine and prednisone). Recently a significant improvement of outcome has been obtained by combining a monoclonal anti-CD20 antibody, Rituximab, with chemotherapy. We conducted the retrospective study to evaluate the predictive role of GC or non-GC subtypes in DLBCL patients receiving CHOP or rituximab-CHOP (R-CHOP). We searched the DLBCL patients diagnosed at Daegu Catholic University Hospital between 2000 and 2007. Rituximab was introduced into the treatment since 2003. Both the immunohistochemical and clinical data could be analyzed in forty six patients. According to the expression of CD10, Bcl-6 and MUM-1, we divided DLBCLs into the GC or non-GC subgroups (Blood. 2004;103:275-282). The median follow-up duration was 22.5 months. 21 and 25 patients were received CHOP and R-CHOP, respectively. 12 and 34 patients were classified into the GC and non-GC subgroups. The GC subtype showed a better overall survival (OS) than the non-GC subtype (p=0.046), but not progression-free survival (PFS) (p=0.633). The GC subtype did not predict the outcome in CHOP and R-CHOP group, respectively. In R-CHOP group, the expression of Bcl-6 was associated with a better OS (p=0.033). The GC subtype showed a better OS in low IPI (IPI 0–2) with borderline significance (p=0.054), but not in high IPI group (IPI 3–5) (p=0.429). In conclusion, the GC subtype showed a better OS in whole patients group, but didn’t show the superior outcome than the non-GC subtype in CHOP subgroup or R-CHOP subgroup, respectively, in this study. It may be due to the small size of the GC subtype. The prospective, large scale study is recommended.

scholarly journals The role of IL-5 in eosinophils’ apoptotic death mechanisms in patients with bronchial asthma

2003 ◽  
Vol 2 (2) ◽  
pp. 38-43
Author(s):  
I. I. Ivanchuk ◽  
A. E. Sazonov ◽  
F. I. Petrovsky ◽  
I. S. Lescheva ◽  
A. P. Kopieva ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Bronchial Asthma ◽  
Peripheral Blood ◽  
Potential Role ◽  
Healthy Donors ◽  
Apoptotic Activity ◽  
Blood Eosinophils ◽  
Cellular Destruction ◽  
Stimulation Of

Investigations of the mRNA expression of apoptosis intracellular regulators, bcl-2 and bcl-xL antagonists and bax, bcl-xL agonists of cellular destruction as well as mRNA expression of IL-5 were carried out. As a result of investigation of potential role of IL-5 in the regulation of programmable bcl-2-dependent destruction we found the increase of vitality and mRNA expression stimulation of bcl-2 peripheral blood eosinophils in patients with bronchial asthma (BA). It was found that fresh-isolated peripheral blood eosinophils in all investigated groups expressed bax and bcl-xL mRNA, bcl-xS had the less activity. In peripheric blood eosinophils of healthy donors the bcl-2 expression was not found, however, the increase of mRNA expression by IL-5 was shown in group of patients with bronchial asthma and, possibly connected with this, the appearance of bcl-2 activity. Thus, the decrease of apoptotic activity in peripheral blood eosinophils in patients with bronchial asthma may lead to the increase of eosinophil portion that is subjected to necrotic destruction and this may significantly contribute into bronchial asthma pathogenesis.

scholarly journals Management of pandemic or large-scale emergencies in Germany with a focus on the current and potential role of university schools of dentistry: Can it help in COVID-19 time?

2020 ◽  
Vol 44 (1) ◽  
Author(s):  
Marcus Schiller ◽  
Marijatta Pilette ◽  
Björn Rahlf ◽  
Constantin von See ◽  
N.-C. Gellrich
Keyword(s):  
Medical Care ◽  
Large Scale ◽  
Potential Role ◽  
Mass Casualty ◽  
Current Status ◽  
Patient Treatment ◽  
Emergency Medical Care ◽  
Emergency Medical ◽  
Available Resources

Abstract Background The study presented here systematically examines the potential involvement of dental, oral and maxillofacial centres (ZMK) in the management of pandemia or in large-scale emergencies. It looks at available material and infrastructural resources and how they can be brought to bear in such incidents or situations. The aim was to gain an initial scientific overview of how ZMK can potentially contribute to the handling of a pandemia or mass casualty (MASCAL) situation in terms of available resources as well as their location within the hospital as a whole and their integration into the existing infrastructure. The study was conducted on the basis of a questionnaire consisting of 70 individual questions, which was sent to all universities in Germany that offer a course of study in dental medicine. The responses were then statistically evaluated. Results The study outlines the current status of ZMK and discusses what could be an important component of emergency medical care in the overall hospital context. Conclusion The involvement of ZMK—with their own resources and existing infrastructural links to the hospital as a whole—could lead to faster and more effective patient treatment in the event of a pandemic or MASCAL situation.

GMP-Grade Large-Scale Expansion of Bone-Marrow- (BM) Derived Human Mesenchymal Stem/Stroma Cells (MSC): Comparison of Efficacy of Different Expansion Systems and Role of Cytokines/Chemokines

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 337-337
Author(s):  
Markus Rojewski ◽  
Natalie Fekete ◽  
Daniel Fuerst ◽  
Philippe Bourin ◽  
Ramin Lotfi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Large Scale ◽  
Buffy Coat ◽  
Single Step ◽  
Adherent Cells ◽  
Transfusion Medicine ◽  
Healthy Donors ◽  
Medium Exchange ◽  
Low Levels

Abstract Abstract 337 Background: MSC cells can differentiate into different tissues and exhibit non-HLA-restricted immunosuppressive properties. They are promising candidates for cellular therapy. Therapeutic use requires large-scale GMP-grade expansion of MSC. Several protocols have been published. Here we systematically compare different expansion procedures with particular emphasis on role of cytokines/chemokines in the expansion medium. Materials and Methods: Bone marrow (BM) was obtained by aspiration from the iliac crest of healthy donors after informed consent and IRB approval. BM aspirate (anticoagulated with heparin (500 U/ml)) was incubated without manipulation in 5-chamber stacks (CellStacks; Corning) in a medium free of animal components (α-MEM (Lonza) with 10% human platelet lysate (hPL)). In the single-step protocol 1.2×104 MNC/ cm2 were seeded. Non-adherent cells were washed off after 72–96 hrs. Partial medium exchange (40%) was performed twice a week (wk). After 11 days MSC were harvested by incubation with recombinant trypsin (TrypZean, Lonza). In the two-step protocol 5×104 leukocytes/cm2 were seeded in 2-chamber stacks. Non-adherent cells were removed after 72–96 hours and complete medium exchange was performed twice/wk. Cells were harvested after 10 days and the harvest was seeded in a 2nd culture at a density of 0.4×104 MSC/cm2. This 2nd culture was harvested after 5 days. Cytokines/chemokines in hPL and in culture medium during the course of expansion was measured by Milliplex MAP Kit (Millipore Corp). Surface marker expression was measured on FACSAria and FACScan. Results: Higher number of MSC could be achieved in cultures with hPL compared to fetal calf serum. hPL was equally effective in supporting MSC proliferation if prepared from apheresis platelet concentrates (PC), buffy coat-derived pooled PC in plasma or pooled PC in additive solution. hPL contained large amounts of PDGF-AB/BB (790 ng/ml; mean of 3 batches of hPL from buffy coat-derived pooled PC), PDGF-AA (266 ng/ml), RANTES (2706 ng/ml), sCD40L (27 ng/ml), GRO (11 ng/ml), sVCAM (2511 ng/ml), sICAM (188 ng/ml). During culture, sCD40L declined rapidly to very low levels. Concentration of PDGF-AA, RANTES and sICAM remained almost stable. In contrast, PDGF-AB/BB declined to low levels (<0.007 ng/ml) in MSC expansion culture whereas concentration remained stable under the same conditions in the absence of MSC. Decline was associated with MSC numbers in the expansion. BM samples from healthy donors (n=4) were split in order to perform paired comparison of single-step vs. two-step expansion protocol. In the single-step protocol 16.3×103±5.8×103 MSC/μl BM seeded were harvested after 11±0 days. In the two-step protocol 12.0×103±4.4×103 MSC/μl BM were harvested after 10 days at the end of passage 0 and 104.0×103±60.4×103 after 5±1 days at the end of passage 1. The overall consumption of medium in the single-step protocol was substantially higher than in the two-step protocol. Phenotype of MSC from the two culture systems did not significantly differ regarding standard markers (positive for CD73, CD90, CD105, HLA-class I; neg. for CD45, CD3, CD34, HLA-DR). However, in passaging experiments we could demonstrate that proportion of MSC positive for CD49a, CD71, CCR4/CD194, CD349 and MSCA-1 decreased whereas proportion of cells positive for c-kit/CD117, CCR3/CD193, CXCR4 and CD200 increased. Conclusion: hPL-based system allows efficient expansion of MSC up to a total number >1×109 MSC from a 15 ml BM aspirate in 2–3 wks with only one passaging step. hPL is a rich source of cytokines, some of which (PDGF-AB/BB) seem to be consumed during expansion and arrive at very low concentrations at the end of the expansion culture. A two-step system provides higher number of MSC per BM cells seeded and requires less medium/culture vessels. Phenotype and differentiation capacity does not differ between single- or two-step culture. However, further passaging goes along with substantial changes of the phenotype. Previous conflicting results regarding chemokine expression of MSC might be due to differences in ex-vivo culture period. Given that chemokine receptor expression affects in-vivo behaviour of cells, MSC harvested after initial expansion (passage 0 or 1) substantially differ from older cells, emphasizing the need to highly standardize all parameters of expansion. (Supported by EU 7th Framework Programme, Projects CASCADE and REBORNE). Disclosures: Fekete: Institute of Clinical Transfusion Medicine and Immunogenetics: Employment. Fuerst:Institute of Clinical Transfusion Medicine and Immunogenetics: Employment. Schrezenmeier:Institute of Clinical Transfusion Medicine and Immunogenetics: Employment.

scholarly journals The Potential Role of Direct Air Capture in the German Energy Research Program—Results of a Multi-Dimensional Analysis

Energies ◽  
2019 ◽  
Vol 12 (18) ◽  
pp. 3443 ◽  
Author(s):  
Peter Viebahn ◽  
Alexander Scholz ◽  
Ole Zelt
Keyword(s):  
Dimensional Analysis ◽  
Research Program ◽  
Large Scale ◽  
Potential Role ◽  
Early Stage ◽  
Energy Research ◽  
Stage Of Development ◽  
Direct Air Capture ◽  
Air Capture

A significant reduction in greenhouse gas emissions will be necessary in the coming decades to enable the global community to avoid the most dangerous consequences of man-made global warming. This fact is reflected in Germany’s 7th Federal Energy Research Program (EFP), which was adopted in 2018. Direct Air Capture (DAC) technologies used to absorb carbon dioxide (CO2) from the atmosphere comprise one way to achieve these reductions in greenhouse gases. DAC has been identified as a technology (group) for which there are still major technology gaps. The intention of this article is to explore the potential role of DAC for the EFP by using a multi-dimensional analysis showing the technology’s possible contributions to the German government’s energy and climate policy goals and to German industry’s global reputation in the field of modern energy technologies, as well as the possibilities of integrating DAC into the existing energy system. The results show that the future role of DAC is affected by a variety of uncertainty factors. The technology is still in an early stage of development and has yet to prove its large-scale technical feasibility, as well as its economic viability. The results of the multi-dimensional evaluation, as well as the need for further technological development, integrated assessment, and systems-level analyses, justify the inclusion of DAC technology in national energy research programs like the EFP.

scholarly journals Collective navigation can facilitate passage through human-made barriers by homeward migrating Pacific salmon

2020 ◽  
Vol 287 (1937) ◽  
pp. 20202137
Author(s):  
Connie Okasaki ◽  
Matthew L. Keefer ◽  
Peter A. H. Westley ◽  
Andrew M. Berdahl
Keyword(s):  
Sockeye Salmon ◽  
Large Scale ◽  
Potential Role ◽  
Pacific Salmon ◽  
Passage Time ◽  
Natural World ◽  
Density Effects ◽  
Mass Migration ◽  
Collective Navigation

The mass migration of animals is one of the great wonders of the natural world. Although there are multiple benefits for individuals migrating in groups, an increasingly recognized benefit is collective navigation, whereby social interactions improve animals’ ability to find their way. Despite substantial evidence from theory and laboratory-based experiments, empirical evidence of collective navigation in nature remains sparse. Here we used a unique large-scale radiotelemetry dataset to analyse the movements of adult Pacific salmon ( Oncorhynchus sp.) in the Columbia River Basin, USA. These salmon face substantial migratory challenges approaching, entering and transiting fishways at multiple large-scale hydroelectric mainstem dams. We assess the potential role of collective navigation in overcoming these challenges and show that Chinook salmon ( O. tshawytscha ), but not sockeye salmon ( O. nerka ) locate fishways faster and pass in fewer attempts at higher densities, consistent with collective navigation. The magnitude of the density effects were comparable to major established drivers such as water temperature, and model simulations predicted that major fluctuations in population density can have substantial impacts on key quantities including mean passage time and fraction of fish with very long passage times. The magnitude of these effects indicates the importance of incorporating conspecific density and social dynamics into models of the migration process. Density effects on both ability to locate fishways and number of passage attempts have the potential to enrich our understanding of migratory energetics and success of migrating anadromous salmonids. More broadly, our work reveals a potential role of collective navigation, in at least one species, to mitigate the effects of anthropogenic barriers to animals on the move.

scholarly journals The Potential Role of News Media to Construct a Machine Learning Based Damage Mapping Framework

2021 ◽  
Vol 13 (7) ◽  
pp. 1401
Author(s):  
Genki Okada ◽  
Luis Moya ◽  
Erick Mas ◽  
Shunichi Koshimura
Keyword(s):  
Machine Learning ◽  
News Media ◽  
Disaster Response ◽  
Large Scale ◽  
Potential Role ◽  
Training Data ◽  
Support Vector ◽  
Machine Method ◽  
Sar Imagery

When flooding occurs, Synthetic Aperture Radar (SAR) imagery is often used to identify flood extent and the affected buildings for two reasons: (i) for early disaster response, such as rescue operations, and (ii) for flood risk analysis. Furthermore, the application of machine learning has been valuable for the identification of damaged buildings. However, the performance of machine learning depends on the number and quality of training data, which is scarce in the aftermath of a large scale disaster. To address this issue, we propose the use of fragmentary but reliable news media photographs at the time of a disaster and use them to detect the whole extent of the flooded buildings. As an experimental test, the flood occurred in the town of Mabi, Japan, in 2018 is used. Five hand-engineered features were extracted from SAR images acquired before and after the disaster. The training data were collected based on news photos. The date release of the photographs were considered to assess the potential role of news information as a source of training data. Then, a discriminant function was calibrated using the training data and the support vector machine method. We found that news information taken within 24 h of a disaster can classify flooded and nonflooded buildings with about 80% accuracy. The results were also compared with a standard unsupervised learning method and confirmed that training data generated from news media photographs improves the accuracy obtained from unsupervised classification methods. We also provide a discussion on the potential role of news media as a source of reliable information to be used as training data and other activities associated to early disaster response.

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