267 research outputs found

    Plasmin Inhibitor in Health and Diabetes: Role of the Protein as a Therapeutic Target

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    The vascular obstructive thrombus is composed of a mesh of fibrin fibers with blood cells trapped in these networks. Enhanced fibrin clot formation and/or suppression of fibrinolysis are associated with an increased risk of vascular occlusive events. Inhibitors of coagulation factors and activators of plasminogen have been clinically used to limit fibrin network formation and enhance lysis. While these agents are effective at reducing vascular occlusion, they carry a significant risk of bleeding complications. Fibrin clot lysis, essential for normal hemostasis, is controlled by several factors including the incorporation of antifibrinolytic proteins into the clot. Plasmin inhibitor (PI), a key antifibrinolytic protein, is cross-linked into fibrin networks with higher concentrations of PI documented in fibrin clots and plasma from high vascular risk individuals. This review is focused on exploring PI as a target for the prevention and treatment of vascular occlusive disease. We first discuss the relationship between the PI structure and antifibrinolytic activity, followed by describing the function of the protein in normal physiology and its role in pathological vascular thrombosis. Subsequently, we describe in detail the potential use of PI as a therapeutic target, including the array of methods employed for the modulation of protein activity. Effective and safe inhibition of PI may prove to be an alternative and specific way to reduce vascular thrombotic events while keeping bleeding risk to a minimum

    Impact of COVID-19 on Construction Projects: The Case of India

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    The COVID-19 pandemic has affected the whole world, including India, especially in the construction sector. The study aims to identify, compare, and analyze the critical pandemic impacts (CPI) on construction projects in India. To achieve this, 40 interviews with industry professionals, are followed by a systematic review to identify the CPI. The data collected was used to develop a survey, sent to industry professionals all over India, with a return of 92 valid responses. The data were analyzed using reliability analysis, mean score ranking, overlap analysis, agreement analysis, and correlation analysis. The overall critical pandemic impact includes ‘labor scarcity,’ ‘supply chain disruption,’ ‘decreased construction productivity,’ ‘increased project financing rejection rate,’ and ‘reduced foreign investment in the construction industry.’ The findings could aid authorities and policymakers in taking suitable actions toward solving the current CPI in India. Project managers and owners could consider the current CPI in order to formulate better plans. Overcoming CPI could lead to an economic leap in India

    Systemic Review and Clinical Management in Diagnosis and Treatment of the Iron Deficiency Anemia in Adults

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    This study aimed at exploring with a systematic review the clinical management in diagnosis and treatment of the iron deficiency anemia in adults, as the iron deficiency is the most frequent cause of anemia worldwide. And it impairs quality of life, increases asthenia and can lead to clinical worsening of patients. In addition, iron deficiency has a complex mechanism whose pathologic pathway is recently becoming better understood. This review summarizes the current knowledge regarding diagnostic algorithms for iron deficiency anemia. The majority of aetiologies occur in the digestive tract, and justify morphological examination of the gut. First line investigations are upper gastrointestinal endoscopy and colonoscopy, and when negative, the small bowel should be explored; newer tools such as video capsule endoscopy have also been developed. The treatment of iron deficiency is aetiological if possible and iron supplementation whether in oral or in parenteral form

    Temperature dependence on the mass susceptibility and mass magnetization of superparamagnetic Mn–Zn–ferrite nanoparticles as contrast agents for magnetic imaging of oil and gas reservoirs

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    The mass susceptibility (χmass) and mass magnetization (Mmass) were determined for a series of ternary manganese and zinc ferrite nanoparticles (Mn–Zn ferrite NPs, MnxZn1−xFe2O4) with different Mn:Zn ratios (0.08 ≤ x ≤ 4.67), prepared by the thermal decomposition reaction of the appropriate metal acetylacetonate complexes, and for the binary homologs (MxFe3−xO4, where M = Mn or Zn). Alteration of the Mn:Zn ratio in Mn–Zn ferrite NPs does not significantly affect the particle size. At room temperature and low applied field strength the mass susceptibility increases sharply as the Mn:Zn ratio increases, but above a ratio of 0.4 further increase in the amount of manganese results in the mass susceptibility decreasing slightly, reaching a plateau above Mn:Zn ≈ 2. The compositional dependence of the mass magnetization shows less of a variation at room temperature and high applied fields. The temperature dependence of the mass magnetization of Mn–Zn ferrite NPs is significantly less for Mn-rich compositions making them more suitable for downhole imaging at higher temperatures (>100 °C). For non-shale reservoirs, replacement of nMag by Mn-rich Mn–Zn ferrites will allow for significant signal-to-noise enhancement of 6.5× over NP magnetite

    European propolis is highly active against trypanosomatids including Crithidia fasciculata.

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    Extracts of 35 samples of European propolis were tested against wild type and resistant strains of the protozoal pathogens Trypanosoma brucei, Trypanosoma congolense and Leishmania mexicana. The extracts were also tested against Crithidia fasciculata a close relative of Crithidia mellificae, a parasite of bees. Crithidia, Trypanosoma and Leishmania are all members of the order Kinetoplastida. High levels of activity were obtained for all the samples with the levels of activity varying across the sample set. The highest levels of activity were found against L. mexicana. The propolis samples were profiled by using liquid chromatography with high resolution mass spectrometry (LC-MS) and principal components analysis (PCA) of the data obtained indicated there was a wide variation in the composition of the propolis samples. Orthogonal partial least squares (OPLS) associated a butyrate ester of pinobanksin with high activity against T. brucei whereas in the case of T. congolense high activity was associated with methyl ethers of chrysin and pinobanksin. In the case of C. fasciculata highest activity was associated with methyl ethers of galangin and pinobanksin. OPLS modelling of the activities against L. mexicana using the mass spectrometry produced a less successful model suggesting a wider range of active components

    Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination

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    Background and purpose Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. Methods Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided. Results Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. Conclusions NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels

    Controlled depolymerisation, as assessed by analytical ultracentrifugation, of low molecular weight chitosan for potential use in archaeological conservation

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    The heterogeneity and molecular weight of a chitosan of low molecular weight (molar mass) and low degree of acetylation (0.1), for potential use as a consolidant for decayed archaeological wood, has been examined by sedimentation velocity and sedimentation equilibriumin the analytical ultracentrifuge before and after depolymerisation. Sedimentation velocity before polymerisation revealed a uniform distribution of sedimentation coefficient with little concentration dependence. SEDFIT-MSTAR analysis revealed a weight average molecular weight Mw of (14.2 + 1.2) kDa, and polydispersity index of ~ 1.2. Further analysis using MULTISIG revealed a distribution of material between 2-20 kDa and consistent with the weight average Mw. Controlled depolymerisation using hydrogen peroxide and UV in an acetic acid medium reduced this to (4.9 + 0.7) kDa, with a similar polydispersity. The depolymerised material appears to be within the range that has been predicted to fully penetrate into archaeological wood. The consequences for this and the use of the analytical ultracentrifuge in wood conservation strategies is considered
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