Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening blood disorder, primarily resulting from autoantibodies against ADAMTS13. Infection or inflammation often precedes acute iTTP. ...However, the association of inflammation and inflammatory mediators with disease severity and outcome of acute iTTP is not fully assessed.
Here, we determined plasma levels of S100A8/A9, histone/DNA complexes, citrullinated histone H3 (CitH3), and cell-free DNA (cfDNA) in a cohort of 108 acute episodes from 94 unique iTTP patients and healthy controls, and assessed the association of each of these biomarkers with the disease severity and mortality.
All acute iTTP patients had significantly increased plasma levels of S100A8/A9 (median 84.8, interquartile range IQR 31.2-157.4 µg/mL), histone/DNA complexes (median 55.7, IQR 35.8-130.8 U/mL), CitH3 (median 3.8, IQR 2.2-6.4 ng/mL), and cfDNA (median 937.7, IQR 781.3-1420.0 ng/mL) on the admission blood samples when compared with healthy controls. An increased plasma level of S100A8/A9, histone/DNA complex and cfDNA was associated with organ damage, coagulopathy, and mortality in iTTP. After being adjusted for age and history of hypertension, Cox proportional hazard regression analysis demonstrated that a hazard ratio (95% confidence interval) for an elevated plasma level of S100A8/A9, histone/DNA complexes, and cfDNA was 11.5 (1.4-90.9) (P = .021), 10.3 (2.7-38.5) (P = .001), and 12.8 (3.9-42.0) (P = .014), respectively.
These results indicate that inflammation or plasma inflammatory mediators such as S100A8/A9 or NETosis markers such as histone/DNA complexes and cfDNA may play a role in pathogenesis of iTTP, which may help stratify patients with a high risk of death during acute iTTP episodes.
Fe(II)NTA
−
(NTA, nitrilotriacetic acid) may lose its ability to bind NO due to the oxidation of Fe(II)NTA
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to Fe(III)NTA by oxygen in the flue gases. NO removal efficiency will decrease quickly ...because of the decline of Fe(II)NTA
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concentration. Activated carbon is used to catalyze the reduction of Fe(III)NTA to Fe(II)NTA
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by sulfite to retain the ability of absorbing NO in the simultaneous removal of NO and SO
2
. Ethylenediamine solution is capable of changing the physical structure and chemical characteristics on the carbon surface to improve the catalytic capability of activated carbon. The experiments suggest that the best activated carbon be generated by immersing the original carbon in 5.0 mol L
−1
ethylenediamine solution for 6 h followed by being heated at 700 °C in N
2
for 4 h. The modification with ethylenediamine increases the surface area and alkalinity on the carbon. The experiments also indicate that the removal efficiency of nitric oxide is increased from 52.1–54.4 to 73.7–77.3% as the Fe(II)NTA
−
regeneration is catalyzed by the modified carbon instead of the original one.
Heparin-induced thrombocytopenia (HIT) is characterized by a high incidence of thrombosis, unlike other antibody-mediated causes of thrombocytopenia. We have shown that monocytes complexed with ...surface-bound platelet factor 4 (PF4) activated by HIT antibodies contribute to the prothrombotic state in vivo, but the mechanism by which this occurs and the relationship to the requirement for platelet activation via fragment crystallizable (Fc)γRIIA is uncertain. Using a microfluidic model and human or murine blood, we confirmed that activation of monocytes contributes to the prothrombotic state in HIT and showed that HIT antibodies bind to monocyte FcγRIIA, which activates spleen tyrosine kinase and leads to the generation of tissue factor (TF) and thrombin. The combination of direct platelet activation by HIT immune complexes through FcγRIIA and transactivation by monocyte-derived thrombin markedly increases Annexin V and factor Xa binding to platelets, consistent with the formation of procoagulant coated platelets. These data provide a model of HIT wherein a combination of direct FcγRIIA-mediated platelet activation and monocyte-derived thrombin contributes to thrombosis in HIT and identifies potential new targets for lessening this risk.
•The procoagulant nature of HIT can be simulated in a microfluidic model using human blood and its components.•PF4/glycosaminoglycans/immunoglobulin G complexes activate monocytes through FcγRIIA to generate TF and thrombin, leading to coated platelets in HIT.
Despite advances in treatment options for thrombotic thrombocytopenic purpura (TTP), there are still limited high quality data to inform clinicians regarding its management.
In June 2018, the ISTH ...formed a multidisciplinary guideline panel to issue recommendations about treatment of TTP. The panel discussed 12 treatment questions related to both immune-mediated TTP (iTTP) and hereditary/congenital TTP (cTTP). The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including evidence-to-decision frameworks, to appraise evidence and formulate recommendations.
The panel agreed on eleven recommendations based on evidence ranging from very low to moderate certainty. For first episode and relapses of acute iTTP, the panel made a strong recommendation for the addition of corticosteroids to therapeutic plasma exchange (TPE), and a conditional recommendation for addition of rituximab and caplacizumab. For asymptomatic iTTP with low ADAMTS13, the panel made a conditional recommendation for rituximab outside of pregnancy, and for prophylactic TPE during pregnancy. For asymptomatic cTTP, the panel made a strong recommendation for prophylactic plasma infusion during pregnancy, but a conditional recommendation for plasma infusion or a wait and watch approach outside of pregnancy.
The panel's recommendations are based on all the available evidence for the treatment effects of various approaches including suppressing inflammation, blocking platelet clumping, replacing the missing and/or inhibited ADAMTS13, and suppressing ADAMTS13 antibody production. There was insufficient evidence for further comparison of different treatment approaches, for which future high-quality studies in iTTP (e.g., rituximab, corticosteroids, recombinant ADAMTS13, and caplacizumab) and in cTTP (eg, recombinant ADAMTS13) are needed.
Synovial chondromatosis (SC) of the temporomandibular joint (TMJ) is a rare benign disease associated with the formation of multiple cartilaginous nodules in the synovial tissue of the TMJ. This can ...result in pain, swelling, clicking, limited mouth opening, and osseous degenerative joint changes. A retrospective cross-sectional study was performed to summarize the clinical features, radiographic findings, and surgical and histopathological findings of TMJ SC patients who underwent open surgery over a 24-year period. A radiographic scoring system was used to evaluate osseous changes and correlate condyle and joint fossa degeneration. The study included 38 patients and focused on 38 joints. All 38 of these joints showed degenerative changes in the condyle, while 37 showed osseous degenerative changes in the articular fossa. The degree of condylar degenerative changes was related to the duration of the chief complaints (r = 0.342, P = 0.036) and the histopathological stage of the TMJ SC (r = 0.440, P = 0.006), while the degree of joint fossa degenerative changes was associated with the radiographic extent of the SC (r = 0.504, P = 0.001), type of calcification (r = 0.365, P = 0.024), and the histopathological stage (r = 0.458, P = 0.004).
•Strain ratio effect on low-cycle fatigue of 7050-T6 aluminium alloy is studied.•Mean stress relaxation rates have been modelled via second order logarithm functions.•Softening degree has been ...correlated with the strain amplitude and strain ratio by a linear relationship.•Low-cycle fatigue lifetime expectancy reduces with increasing values of strain ratio.
This paper aims at investigating the strain ratio effect on cyclic deformation behaviour of 7050-T6 aluminium alloy. Low-cycle fatigue tests are conducted under strain-controlled conditions at three strain ratios (−1, 0, and 0.5) with strain amplitudes in the range 0.60–1.75%. Microstructure is analysed by optical microscopy, transmission electron microscopy and X-ray diffraction, and fracture surfaces are examined by scanning electron microscopy and transmission electron microscopy. The results show that the material exhibits a cyclic strain-softening behaviour whose degree increases with increasing values of strain ratio and decreasing values of strain amplitude. Under non-zero mean strain, full relaxation of mean stress is only observed at higher strain amplitudes. A second order logarithmic model is proposed to account for the mean stress relaxation rates. Lifetime expectancy is reduced as the strain ratio raises which is consistent with the progressive increment of fatigue striation spacing observed in the fractographic analyses.
Proteolytic cleavage of von Willebrand factor (VWF) by a plasma a disintegrin and metalloproteinase with a thrombospondin type 1 motifs, member 13 (ADAMTS13) is regulated by shear stress and binding ...of coagulation factor VIII, platelets or platelet glycoprotein 1b, and ristocetin to VWF.
Current study aims to identify novel VWF binding partners that may modulate VWF functions under physiological conditions.
A deoxyribonucleic acid aptamer-based affinity purification of VWF, followed by tandem mass spectrometry, functional, and binding assays was employed.
Apolipoprotein B100/low-density lipoprotein (apoB100/LDL) was identified as a novel VWF-binding partner. Purified apoB100/LDL was able to accelerate the proteolytic cleavage of VWF by ADAMTS13 under shear in a concentration-dependent manner. This rate-enhancing activity was dramatically reduced when apoB100/LDL was oxidized. More interestingly, the oxidized apoB100/LDL appeared to compete with native apoB100/LDL for its enhancing activity on VWF proteolysis under shear. As a control, a purified apoA1/high-density lipoprotein (apoA1/HDL) or apoB48 exhibited a minimal or no activity enhancing VWF proteolysis by ADAMTS13 under the same conditions. Both VWF and ADAMTS13 were able to bind native or oxidized apoB100/LDL with high affinities. No binding interaction was detected between VWF (or ADAMTS13) and apoA1/HDL (or apoB48). Moreover, apoB100/LDL but not its oxidized products inhibited the adhesion of platelets to ultra large VWF released from endothelial cells under flow. Finally, significantly reduced ratios of high to low molecular weight of VWF multimers with increased levels of plasma VWF antigen were detected in
mice fed with high cholesterol diet.
These results indicate that apoB100/LDL may be a novel physiological regulator for ADAMTS13-VWF functions.
Immune-mediated thrombotic thrombocytopenic purpura is characterized by severe thrombocytopenia and microangiopathic hemolytic anemia. It is primarily caused by immunoglobin G type autoantibodies ...against ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. However, reliable markers predictive of patient outcomes are yet to be identified. Seventy-three unique patients with a confirmed diagnosis of immune-mediated thrombotic thrombocytopenic purpura between April 2006 and December 2017 were enrolled from the Univeristy of Alabama at Birmingham Medical Center. Clinical information, laboratory values, and a panel of special biomarkers were collected and/or determined. The results demonstrated that the biomarkers associated with endothelial injury (e.g., von Willebrand factor antigen and collagen-binding activity), acute inflammation (e.g., human neutrophil peptides 1-3 and histone/deoxyribonucleic acid complexes), and activation of the complement alternative pathway (e.g., factors Bb and iC3b) were all significantly increased in patients with acute immune-mediated thrombotic thrombocytopenic purpura compared to those in the healthy controls. Moreover, failure to normalize platelet counts within 7 days or failure to markedly reduce serum lactate dehydrogenase by day 5, low total serum protein or albumin, and high serum troponin levels were also predictive of mortality, as were the prolonged activated partial thromboplastin time, high fibrinogen, and elevated serum lactate dehydrogenase, Bb, and sC5b-9 on admission. These results may help to stratify patients for more intensive management. The findings may also provide a framework for future multicenter studies to identify valuable prognostic markers for immune-mediated thrombotic thrombocytopenic purpura.
The feasibility of using vibration transfer rate as damage parameter is studied by simulation. The excitation mode, sensitive measuring point, structural adhesive damage identification and safety ...state evaluation of hidden frame glass curtain wall (HFGCW) are studied by experiment. The experimental results show that the accurate vibration spectrum can be obtained by using rubber hammer. The edge of glass plate is selected as the measuring point to obtain the accurate vibration transfer rate. The value of change rate of vibration transmissibility increases with the increase in damage degree of structural adhesive. A nondestructive testing method combining vibration transfer rate and discrete wavelet transform (DWT) is proposed, which can identify the degree of structural adhesive damage of HFGCW well. At the same time, the safety status evaluation model based on vibration transfer rate can evaluate the damage degree of structural adhesive of HFGCW.
Background: Endotheliopathy is a common pathologic finding in patients with acute and long COVID-19. It may be associated with disease severity and predispose patients to long-term complications. ...Plasma levels of a proteoglycan, syndecan-1, are found to be significantly elevated in patients with COVID-19, but its roles in assessing disease severity and predicting long-term outcome are not fully understood. Methods: A total of 124 consecutive hospitalized patients with SARS-CoV-2 infection were prospectively enrolled and blood samples were collected on admission (T1), 3−4 days following treatment (T2), and 1−2 days prior to discharge or death (T3). Plasma levels of syndecan-1 were determined using an immunosorbent assay; various statistical analyses were performed to determine the association between plasma syndecan-1 levels and disease severity or the 60-day mortality rate. Results: Compared with those in the healthy controls, plasma levels of syndecan-1 in patients with critical COVID-19 were significantly higher (p < 0.0001). However, there was no statistically significant difference among patients with different disease severity (p > 0.05), resulting from large individual variability. Longitudinal analysis demonstrated that while the levels fluctuated during hospitalization in all patients, plasma syndecan-1 levels were persistently elevated from baseline in critical COVID-19 patients. Cox proportional hazard regression analyses revealed that elevated plasma levels of syndecan-1 (>260 ng/mL at T1, >1018 ng/mL at T2, and >461 ng/mL at T3) were significantly associated with the 60-day mortality rate. Conclusions: Endotheliopathy, marked by glycocalyx degradation and elevated plasma syndecan-1, occurs in nearly all hospitalized patients with SARS-CoV-2 infection; elevated plasma syndecan-1 is associated with increased mortality in COVID-19 patients.
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