Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity in targeting phospholipids and phospholipid-binding proteins. The persistent ...presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2-glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by-among other factors-viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL with prothrombin (PT). The strength of the antibody response against SARS-CoV-2 was further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity, and aPL against PT in patients with SARS-CoV-2.
For about five decades, the United Nations Population Division has produces a comprehensive demographic account of the global urbanization process, now known as the biennial “World Urbanization ...Prospects”. This article describes the evolution of this unique data source from its inception to its 19th issues as the 2011 Revision and gives an overview about the statistical data sources used for the estimation of past and future trends, the models used for estimation and projection and the tools that have been developed to carry out the tasks. The article finally discusses the as yet unsuccessful demand for more compatible and comparable statistical definition or urban and city populations, addresses some alternative approaches and offers some ideas about possible improvements to the current methodology.
Systemic administration of hypoxia-selective64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) has increased significantly the survival time of hamsters bearing human GW39 colon cancer tumors. ...Radiotherapy experiments were performed in animals bearing either 7-day-old (0.5-1.0 g) or 15-day-old (1.5-2.0 g) tumors. Studies compared animals treated with a single dose of 0, 4, 6, 7, 8, or 10 mCi of64Cu-ATSM (1 Ci = 37 GBq) with or without the vasodilator hydralazine. A multiple dose regimen of 3 x 4 mCi at 72-h intervals was studied also. Single doses of >6 mCi of64Cu-ATSM and the dose-fractionation protocol significantly increased the survival time of the hamsters compared with controls. The highest dose, 10 mCi of64Cu-ATSM, increased survival to 135 days in 50% of animals bearing 7-day-old tumors, 6-fold longer than control animals' survival (20 days), with only transient leucopenia and thrombocytopenia but no overt toxicity. Human absorbed doses were calculated from hamster biodistribution; the dose-critical organs were the lower large intestine (1.43 ± 0.19 rad/mCi) and upper large intestine (1.20 ± 0.38 rad/mCi). High-resolution MRI and positron-emission tomography using a therapeutic administration of 10 mCi were used to monitor tumor volume and morphology and to assess tumor dosimetry accurately, giving a tumor dose of 81 ± 7.5 rad/mCi.64Cu-ATSM has increased the survival time of tumor-bearing animals significantly with no acute toxicity and thus is a promising agent for radiotherapy.
The aim of this study was to evaluate a novel third‐generation enzyme‐linked immunosorbent assay (ELISA) for the high‐sensitivity detection of autoantibodies to proteinase‐3 (PR3) in patients with ...Wegener's granulomatosis (WG). First‐ and second‐generation ELISA for the detection of antineutrophil cytoplasmic antibodies (ANCA) frequently demonstrate insufficient sensitivity due to inadequate presentation of autoantigenic epitopes. Human PR3 was immobilized on the solid phase of ELISA plates by anchoring technique. Anti‐PR3 reactivity was measured in 34 C‐ANCA positive patients with WG, 11 MPO‐ANCA–positive patients with other autoimmune vasculitides, 65 patients with systemic lupus erythematosus (SLE), and 137 healthy blood donors. Thirty‐three of 34 patients with WG (97.1%) showed positive anti‐PR3 IgG antibody reactivity. None of 11 MPO‐ANCA positive vasculitis patients, none of 137 blood donors, and 3 of 65 SLE patients expressed elevated IgG reactivity to PR3 (specificity: 98.4%). Comparison with another third‐generation ELISA did not reveal different qualitative results. However, there was no significant correlation between quantitative results of both assays. Receiver operating characteristic (ROC) curve analysis revealed a significantly better assay performance compared with first (direct)‐ and second (capture)‐generation assays (P= 0.011 and P= 0.001, respectively). Third‐generation (anchor) anti‐PR3 ELISA exhibit significantly higher sensitivity than previous generation assays. Anchoring of PR3 renders the granulocyte protein more autoantigenic compared with direct or capture immobilization.
Background
Common marmosets (Callithrix jacchus) are susceptible to gastrointestinal diseases. Sensitivity to nutritional elements, for example gluten, has been suggested, but a serological screening ...has not been performed yet.
Methods
A gluten‐containing diet was offered to 24 animals, followed by a gluten‐free diet. During these diets, serum IgA antibodies to gliadin (AGA), tissue transglutaminase (tTG), deamidated gliadin (ADGA), and glycoprotein 2 (AGP2A) were determined. Body weight, diarrhea, and other clinical symptoms were recorded.
Results
Gluten increased AGA, tTG, and AGP2A concentrations in 13 of 24 animals. A significant decline of AGA and AGP2A was seen on gluten withdrawal. Positive (AGA, tTG) animals presented diarrhea more frequently on gluten‐containing diet and showed significantly increased body weight on gluten‐free diet compared to negative animals.
Conclusion
Gluten ingestion caused gastrointestinal symptoms in common marmosets, which disappeared on gluten withdrawal. Considering the immunological response to both diets, gluten sensitivity seems to be most likely.
World population stabilization unlikely this century Gerland, Patrick; Raftery, Adrian E.; Ševčíková, Hana ...
Science (American Association for the Advancement of Science),
10/2014, Letnik:
346, Številka:
6206
Journal Article
Recenzirano
Odprti dostop
The United Nations (UN) recently released population projections based on data until 2012 and a Bayesian probabilistic methodology. Analysis of these data reveals that, contrary to previous ...literature, the world population is unlikely to stop growing this century. There is an 80% probability that world population, now 7.2 billion people, will increase to between 9.6 billion and 12.3 billion in 2100. This uncertainty is much smaller than the range from the traditional UN high and low variants. Much of the increase is expected to happen in Africa, in part due to higher fertility rates and a recent slowdown in the pace of fertility decline. Also, the ratio of working-age people to older people is likely to decline substantially in all countries, even those that currently have young populations.
Abstract
Binary iron‐germanium phases are promising materials in magnetoelectric, spintronic or data storage applications due to their unique magnetic properties. Previous protocols for preparation ...of Fe
x
Ge
y
thin films and nanostructures typically involve harsh conditions and are challenging in terms of phase composition and homogeneity. Herein, we report the first example of single source chemical vapor deposition (CVD) of Fe
x
Ge
y
films. The appreciable volatility of GeFe
2
(CO)
8
2
, Cl
2
GeFe(CO)
4
2
and
Me₂iPr₂
NHC ⋅ GeCl
2
⋅ Fe(CO)
4
allowed for their application as precursors under standard CVD conditions (
Me₂iPr₂
NHC=1,3‐diisopropoyl‐4,5‐dimethylimidazol‐2‐ylidene). The thermal decomposition products of the precursors were characterized by TGA and powder XRD. Deposition experiments in a cold‐wall CVD reactor resulted in dense films of Fe
x
Ge
y
. During the optimization of synthetic conditions for precursor preparation the new iron‐germanium cluster Cl
2
GeFe
2
(CO)
8
GeFe
2
(CO)
8
was obtained in experiments with a higher stoichiometric ratio of GeCl
2
⋅ 1,4‐dioxane vs. Fe
2
(CO)
9
.
The antibody-drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients with metastatic ...urothelial carcinoma (mUC) without prior assessment of the tumor receptor status as ubiquitous NECTIN-4 expression is assumed. Our objective was to determine the prevalence of membranous NECTIN-4 protein expression in primary tumors (PRIM) and patient-matched distant metastases (MET).
Membranous NECTIN-4 protein expression was measured (H-score) by IHC in PRIM and corresponding MET (N = 137) and in a multicenter EV-treated cohort (N = 47). Progression-free survival (PFS) after initiation of EV treatment was assessed for the NECTIN-4-negative/weak (H-score 0-99) versus moderate/strong (H-score 100-300) subgroup. The specificity of the NECTIN-4 IHC staining protocol was validated by establishing CRISPR-Cas9-induced polyclonal NECTIN-4 knockouts.
In our cohort, membranous NECTIN-4 expression significantly decreased during metastatic spread (Wilcoxon matched pairs P < 0.001; median H-score = 40; interquartile range, 0-140), with 39.4% of MET lacking membranous NECTIN-4 expression. In our multicenter EV cohort, absence or weak membranous NECTIN-4 expression (34.0% of the cohort) was associated with a significantly shortened PFS on EV (log-rank P < 0.001).
Membranous NECTIN-4 expression is frequently decreased or absent in mUC tissue. Of note, the clinical benefit of EV strongly depends on membranous NECTIN-4 expression. Thus, our results are of highest clinical relevance and argue for a critical reconsideration of the current practice and suggest that the NECTIN-4 receptor status should be determined (ideally in a metastatic/progressive lesion) before initiation of EV. See related commentary by Aggen et al., p. 1377.
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