Abstract
Background
Fibrin(ogen) amyloid microclots and platelet hyperactivation previously reported as a novel finding in South African patients with the coronavirus 2019 disease (COVID-19) and Long ...COVID/Post-Acute Sequelae of COVID-19 (PASC), might form a suitable set of foci for the clinical treatment of the symptoms of Long COVID/PASC. A Long COVID/PASC Registry was subsequently established as an online platform where patients can report Long COVID/PASC symptoms and previous comorbidities.
Methods
In this study, we report on the comorbidities and persistent symptoms, using data obtained from 845 South African Long COVID/PASC patients. By using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we also analysed blood samples from 80 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases.
Results
Hypertension, high cholesterol levels (dyslipidaemia), cardiovascular disease and type 2 diabetes mellitus (T2DM) were found to be the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. These findings confirmed that our sample was not atypical. Microclot and platelet pathologies were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19.
Conclusions
Fibrin amyloid microclots that block capillaries and inhibit the transport of O
2
to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest that our platelet and clotting grading system provides a simple and cost-effective diagnostic method for early detection of Long COVID/PASC as a major determinant of effective treatment, including those focusing on reducing clot burden and platelet hyperactivation.
The formations of intrinsic n-type defects, that is, oxygen vacancies and titanium interstitials, in rutile and anatase TiO2 have been compared using GGA+U calculations. In both crystal structures, ...these defects give rise to states in the band gap, corresponding to electrons localized at Ti3+ centers. O vacancy formation in rutile results in two excess electrons occupying 3d orbitals on Ti atoms neighboring the vacancy. Similarly, for anatase, two Ti 3d orbitals are occupied by the excess electrons, with one of these Ti sites neighboring the vacancy, and the second at a next-nearest Ti position. This localization is accompanied by one oxygen moving toward the vacancy site to give a “split vacancy” geometry. A second fully localized solution is also found for anatase, with both occupied Ti sites neighboring the vacancy site. This minimum is 0.05 eV less stable than the split vacancy and is thus expected to be present in experimental samples. A partially delocalized solution corresponding to the split vacancy geometry, with one electron occupying the bottom of the conduction band, is also identified as 0.28 eV less stable. Formation of titanium interstitials donates four electrons to the Ti lattice. In anatase, one of these electrons is located at the interstitial Ti site, and three occupied defect states are hybridized between three nearest neighbor Ti sites. In rutile, these excess electrons are mostly localized at four nearest neighbor Ti sites, with only a small amount of excess charge found on the interstitial Ti atom. This difference in the charge on the interstitial atom is a consequence of the differing interstitial geometries in the two polymorphs. Calculated optical absorption spectra for all defects show significant decreases of the optical band gap, with a larger red shift predicted for titanium interstitials in anatase than in rutile. Defect formation energies have been calculated under oxygen-rich and oxygen-poor conditions for both polymorphs. Under all conditions, O vacancy formation is slightly more favorable in anatase than in rutile, while Ti interstitials form more easily in rutile than anatase. Under O-rich conditions, O vacancies are the favored defect type, but both defect types have high formation energies. Under O-poor conditions, both defect types are stabilized, with Ti interstitials predicted to become the favored defect in rutile samples, particularly at elevated temperatures.
Experimental observations indicate that removing bridging oxygen atoms from the TiO2 rutile (110) surface produces a localised state approximately 0.7eV below the conduction band. The corresponding ...excess electron density is thought to localise on the pair of Ti atoms neighbouring the vacancy; formally giving two Ti3+ sites. We consider the electronic structure and geometry of the oxygen deficient TiO2 rutile (110) surface using both gradient-corrected density functional theory (GGA DFT) and DFT corrected for on-site Coulomb interactions (GGA+U) to allow a direct comparison of the two methods. We show that GGA fails to predict the experimentally observed electronic structure, in agreement with previous uncorrected DFT calculations on this system. Introducing the +U term encourages localisation of the excess electronic charge, with the qualitative distribution depending on the value of U. For low values of U (4.0eV) the charge localises in the sub-surface layers occupied in the GGA solution at arbitrary Ti sites, whereas higher values of U (4.2eV) predict strong localisation with the excess electronic charge mainly on the two Ti atoms neighbouring the vacancy. The precise charge distribution for these larger U values is found to differ from that predicted by previous hybrid-DFT calculations.
Probing Cold Dense Nuclear Matter Subedi, R; Shneor, R; Monaghan, P ...
Science (American Association for the Advancement of Science),
06/2008, Letnik:
320, Številka:
5882
Journal Article
Recenzirano
The protons and neutrons in a nucleus can form strongly correlated nucleon pairs. Scattering experiments, in which a proton is knocked out of the nucleus with high-momentum transfer and high missing ...momentum, show that in carbon-12 the neutron-proton pairs are nearly 20 times as prevalent as proton-proton pairs and, by inference, neutron-neutron pairs. This difference between the types of pairs is due to the nature of the strong force and has implications for understanding cold dense nuclear systems such as neutron stars.
With an ageing population, dietary approaches to promote health and independence later in life are needed. In part, this can be achieved by maintaining muscle mass and strength as people age. New ...evidence suggests that current dietary recommendations for protein intake may be insufficient to achieve this goal and that individuals might benefit by increasing their intake and frequency of consumption of high-quality protein. However, the environmental effects of increasing animal-protein production are a concern, and alternative, more sustainable protein sources should be considered. Protein is known to be more satiating than other macronutrients, and it is unclear whether diets high in plant proteins affect the appetite of older adults as they should be recommended for individuals at risk of malnutrition. The review considers the protein needs of an ageing population (>40 years old), sustainable protein sources, appetite-related implications of diets high in plant proteins, and related areas for future research.
Bangladesh exhibits the second highest rate of smokeless tobacco (SLT) product usage in the world, and this has been associated with the high upper aerodigestive tract cancer incidence in this ...country. The goal of the present study was to examine the levels of the highly carcinogenic tobacco-specific nitrosamines (TSNAs) in Bangladeshi SLT products and compare these levels to that observed in SLT brands from southeast Asia and the USA. The levels of TSNAs and nicotine were determined by LC-MS/MS in twenty-eight SLT brands and several tobacco additives from Bangladesh, as well as several SLT brands from India, Pakistan and the USA. The levels of N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosoanatabine (NAT) and N-nitrosoanabasine (NAB) in Bangladeshi SLT brands ranged from 1.1-59, 0.15-34, 0.79-45, and 0.037-13 μg/g SLT powder, respectively. The mean levels of the highly carcinogenic TSNAs (NNN+NNK) were 7.4-, 2.4-, and 63-fold higher in Bangladeshi SLT products as compared to SLT brands from the USA, India and Pakistan, respectively; these trends were also observed for NAT and NAB. Similar mean levels of nicotine were observed in the Bangladeshi brands (31 mg/g powder) versus brands from the USA (25 mg/g powder) and India (20 mg/g powder); they were 3-fold higher than brands from Pakistan (10 mg/g powder). Gul SLT brands exhibited the highest pH and the highest levels of unprotonated nicotine. The high levels of TSNAs in Bangladeshi SLT brands may be an important factor contributing to the high rates of upper aerodigestive tract cancer in Bangladesh.
Cellular stress response mechanisms normally function to enhance survival and allow for cells to return to homeostasis following an adverse event. Cancer cells often co-opt these same mechanisms as a ...means to evade apoptosis and mitigate a state of constant cellular stress. Activating transcription factor 5 (ATF5) is upregulated under diverse stress conditions and is overexpressed in a variety of cancers. It was demonstrated ATF5 is a survival factor in transformed, but not normal cells. However, the regulation of ATF5 is not fully understood. The purpose of the present study was to investigate miRNA regulation at the 3' untranslated region (UTR) of ATF5, with the goal of demonstrating a reversal of the upregulation of ATF5 induced under diverse cellular stress in cancer cells. A multifactorial approach using in silico analysis was employed to identify miRNAs 433-3p, 520b-3p, and 129-5p as potential regulators of ATF5, based on their predicted binding sites over the span of the ATF5 3' UTR. Luciferase reporter assay data validated all three miRNA candidates by demonstrating direct binding to the target ATF5 3'. However, functional studies revealed miR-520b-3p as the sole candidate able to reverse the upregulation of ATF5 protein under diverse cellular stress. Additionally, miR-520b-3p levels were inversely related to ATF5 mRNA under endoplasmic reticulum stress and amino acid deprivation. This is the first evidence that regulation at the 3' UTR is involved in modulating ATF5 levels under cellular stress and suggests an important role for miRNA-520b-3p in the regulation of ATF5.
The regional leptomeningeal score is a strong and reliable imaging predictor of good clinical outcomes in acute anterior circulation ischemic strokes and can therefore be used for imaging based ...patient selection. Efforts to determine biological determinants of collateral status are needed if techniques to alter collateral behavior and extend time windows are to succeed.
This was a retrospective Institutional Review Board-approved study of patients with acute ischemic stroke and M1 middle cerebral artery+/- intracranial internal carotid artery occlusion at our center from 2003 to 2009. The rLMC score is based on scoring pial and lenticulostriate arteries (0, no; 1, less; 2, equal or more prominent compared with matching region in opposite hemisphere) in 6 ASPECTS regions (M1-6) plus anterior cerebral artery region and basal ganglia. Pial arteries in the Sylvian sulcus are scored 0, 2, or 4. Good clinical outcome was defined as mRS ≤ 2 at 90 days.
The analysis included 138 patients: 37.6% had a good (17-20), 40.5% a medium (11-16), and 21.7% a poor (0-10) rLMC score. Interrater reliability was high, with an intraclass correlation coefficient of 0.87 (95% CI, 0.77%-0.95%). On univariate analysis, no single vascular risk factor was associated with the presence of poor rLMCs (P ≥ .20 for all comparisons). In multivariable analysis, the rLMC score (good versus poor: OR, 16.7; 95% CI, 2.9%-97.4%; medium versus poor: OR, 9.2, 95% CI, 1.7%-50.6%), age (< 80 years), baseline ASPECTS (≥ 8), and clot burden score (≥ 8) were independent predictors of good clinical outcome.
The rLMC score is a strong imaging parameter on CT angiography for predicting clinical outcomes in patients with acute ischemic strokes.
The stacked density profile of cosmic voids in the galaxy distribution provides an important tool for the use of voids for precision cosmology. We study the density profiles of voids identified using ...the zobov watershed transform algorithm in realistic mock luminous red galaxy (LRG) catalogues from the Jubilee simulation, as well as in void catalogues constructed from the SDSS LRG and Main Galaxy samples. We compare different methods for reconstructing density profiles scaled by the void radius and show that the most commonly used method based on counts in shells and simple averaging is statistically flawed as it underestimates the density in void interiors. We provide two alternative methods that do not suffer from this effect; one based on Voronoi tessellations is also easily able to account from artefacts due to finite survey boundaries and so is more suitable when comparing simulation data to observation. Using this method, we show that the most robust voids in simulation are exactly self-similar, meaning that their average rescaled profile does not depend on the void size. Within the range of our simulation, we also find no redshift dependence of the mean profile. Comparison of the profiles obtained from simulated and real voids shows an excellent match. The mean profiles of real voids also show a universal behaviour over a wide range of galaxy luminosities, number densities and redshifts. This points to a fundamental property of the voids found by the watershed algorithm, which can be exploited in future studies of voids.
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