Differences between FEV6, FVC and VC at the diagnosis of obstructive ventilatory defect

Introduction: The diagnosis of airway obstruction can be made through FEV1/FVC ratio <0.7 or FEV1/VC ratio < lower limit of normality (LLN). Several authors advocate that FEV1/FEV6 ratio is an alternative to diagnosing obstructive ventilatory defect, while others have determined that the best cut-off for this ratio (best combined sensitivity and specificity) is 0.73. Objective: To evaluate the non-inferiority of FEV1/FEV6 ratio < 0.73 when compared to FEV1/ FVC ratio < 0.7 and FEV1/VC < LLN in diagnosing airway obstruction. Methods: A retrospective analysis of the medical records from patients who underwent spirometry or plethysmography in a university central hospital from June 1st to December 31st, 2018 was carried out. Only medical records which included FEV1/FVC < 0.7 or FEV1/VC < LLN were selected, and these results were compared to FEV1/FEV6 ratio. Results: A total of 526 patients with obstructive ventilatory defect were identified by one of the two ratios described. Of these, 95.1%, 87.4% and 88.6% were obstructive by FEV1/FVC, FEV1/ VC, and FEV1/FEV6 ratio, respectively. The positive predictive value (PPV) of FEV1/FEV6 in relation to FEV1/FVC ratio was 99.6% (p < 0.001) with a diagnostic efficacy of 92.8%, whereas the PPV of FEV1/FEV6 in relation to FEV1/VC was 91.0% (p 70% (mild obstruction) and in individuals aged >50 years. Conclusions: FEV1/FEV6 < 0.73 may be a good alternative ratio, as it is non-inferior to FEV1/VC and FEV1/FVC in diagnosing obstructive ventilatory defect.info:eu-repo/semantics/publishedVersio

Novel Perspectives in Management of Angiogenesis and Cancer Therapy

Funding: The project was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through the project DREAM—PTDC/MEC-ONC/29327/2017. FL-C PhD fellowship was funded by FCT (PD/BD/128337/2017).The activation of endothelial cells (ECs) is a crucial step on the road map of tumor angiogenesis and expanding evidence indicates that a pro-oxidant tumor microenvironment, conditioned by cancer metabolic rewiring, is a relevant controller of this process. Herein, we investigated the contribution of oxidative stress-induced ferroptosis to ECs activation. Moreover, we also addressed the anti-angiogenic effect of Propranolol. We observed that a ferroptosis-like mechanism, induced by xCT inhibition with Erastin, at a non-lethal level, promoted features of ECs activation, such as proliferation, migration and vessel-like structures formation, concomitantly with the depletion of reduced glutathione (GSH) and increased levels of oxidative stress and lipid peroxides. Additionally, this ferroptosis-like mechanism promoted vascular endothelial cadherin (VE-cadherin) junctional gaps and potentiated cancer cell adhesion to ECs and transendothelial migration. Propranolol was able to revert Erastin-dependent activation of ECs and increased levels of hydrogen sulfide (H2S) underlie the mechanism of action of Propranolol. Furthermore, we tested a dual-effect therapy by promoting ECs stability with Propranolol and boosting oxidative stress to induce cancer cell death with a nanoformulation comprising selenium-containing chrysin (SeChry) encapsulated in a fourth generation polyurea dendrimer (SeChry@PUREG4). Our data showed that novel developments in cancer treatment may rely on multi-targeting strategies focusing on nanoformulations for a safer induction of cancer cell death, taking advantage of tumor vasculature stabilization.publishersversionpublishe

Drum vortons in high density QCD

Recently it was shown that high density QCD supports of number of topological defects. In particular, there are U(1)_Y strings that arise due to K^0 condensation that occurs when the strange quark mass is relatively large. The unique feature of these strings is that they possess a nonzero K^+ condensate that is trapped on the core. In the following we will show that these strings (with nontrivial core structure) can form closed loops with conserved charge and currents trapped on the string worldsheet. The presence of conserved charges allows these topological defects, called vortons, to carry angular momentum, which makes them classically stable objects. We also give arguments demonstrating that vortons carry angular momentum very efficiently (in terms of energy per unit angular momentum) such that they might be the important degrees of freedom in the cores of neutron stars.Comment: 11 pages, accepted for publication in Physical Review

Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings

Dimensionless cosmology

Although it is well known that any consideration of the variations of fundamental constants should be restricted to their dimensionless combinations, the literature on variations of the gravitational constant $G$ is entirely dimensionful. To illustrate applications of this to cosmology, we explicitly give a dimensionless version of the parameters of the standard cosmological model, and describe the physics of Big Bang Neucleosynthesis and recombination in a dimensionless manner. The issue that appears to have been missed in many studies is that in cosmology the strength of gravity is bound up in the cosmological equations, and the epoch at which we live is a crucial part of the model. We argue that it is useful to consider the hypothetical situation of communicating with another civilization (with entirely different units), comparing only dimensionless constants, in order to decide if we live in a Universe governed by precisely the same physical laws. In this thought experiment, we would also have to compare epochs, which can be defined by giving the value of any {\it one} of the evolving cosmological parameters. By setting things up carefully in this way one can avoid inconsistent results when considering variable constants, caused by effectively fixing more than one parameter today. We show examples of this effect by considering microwave background anisotropies, being careful to maintain dimensionlessness throughout. We present Fisher matrix calculations to estimate how well the fine structure constants for electromagnetism and gravity can be determined with future microwave background experiments. We highlight how one can be misled by simply adding $G$ to the usual cosmological parameter set

Dynamic Analysis of Unidirectional Pressure Infiltration of Porous Preforms by Pure Metals

Unidirectional pressure infiltration of porous preforms by molten metals is investigated numerically. A phenomenological model to describe fluid flow and transport phenomena during infiltration of fibrous preforms by a metal is formulated. The model describes the dynamics of the infiltration process, the temperature distribution, and solid fraction distribution. The numerical results are compared against classical asymptotic analyses and experimental results. This comparison shows that end effects may become important and render asymptotic results unreliable for realistic samples. Fiber volume fraction and initial temperature appear as the factors most strongly influencing infiltration. Metal superheating affects not only the length of the two-phase zone but also the solid fraction distribution in the two-phase zone. The effect of constant applied pressure, although significant on the infiltration velocity, is almost negligible on the two-phase zone length and on solid fraction distribution. When the initial preform temperature is below the metal melting point, and constant pressure is applied under adiabatic conditions, the flow ceases when sufficient solidification occurs to obstruct it. A comparison with literature experiments proves the model to be an efficient predictive tool in the analysis of infiltration processes for different preform/melt systems

Spatial distribution and evaluation of risk factors for bovine neosporosis in Rondônia, Brazil

ABSTRACT Neospora caninum is an important worldwide parasite responsible for causing abortion in animals. Due to limited information on the occurrence of infection by this parasite in the state of Rondônia, Brazil, this study aimed to determine the seroprevalence and identify the risk factors associated with the infection in slaughtered cattle, from 19 municipalities distributed in seven microregions of the state. A total of 494 samples were obtained and subjected to anti-N. caninum antibodies, using the Indirect Immunofluorescence Reaction technique. Antibodies were detected in 5.06% (25/494) of the samples, in 30.30% (10/33) of farms, in nine municipalities located in four microregions of Rondônia. Of all the animals analyzed, 4.81% of the females (20/416) and 6.41% of the males (05/78) were seropositive for the parasite, with “abortion in the last 12 months” being considered an important risk factor for the occurrence of infection (OR = 9.54; p = 0.01). The present study points out the prevalence of anti-N. caninum antibodies in 5.06% of slaughtered animals and abortion as the main risk factor associated with infection by N. caninum, thus contributing to the elucidation of the epidemiology of this protozoan in Rondônia, Brazil