The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of ...understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO.
We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO.
This is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity <0.70 recruited from outpatient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO. ACO was defined by a history of smoking >10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis.
In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median interquartile range) of IL-5 were higher in asthma patients than in COPD patients (2.09 0.61-3.57 vs 1.11 0.12-2.42 pg/mL, respectively;
=0.03), and IL-8 levels (median interquartile range) were higher in COPD patients than in asthma patients (9.45 6.61-13.12 vs 7.03 4.69-10.44 pg/mL, respectively;
<0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions.
Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions.
Diabetes mellitus is a chronic metabolic disorder, being globally one of the most deadly diseases. This disease requires continually monitoring of the body's glucose levels. There are different types ...of sensors for measuring glucose, most of them invasive to the patient. Fiber optic sensors have been proven to have advantages compared to conventional sensors and they have great potential for various applications, especially in the biomedical area. Compared to other sensors, they are smaller, easy to handle, mostly non-invasive, thus leading to a lower risk of infection, high precision, well correlated and inexpensive. The objective of this review article is to compare different types of fiber optic sensors made with different experimental techniques applied to biomedicine, especially for glucose sensing. Observations are made on the way of elaboration, as well as the advantages and disadvantages that each one could have in real applications.
Recent advancements on the fabrication of organic micro- and nanostructures have permitted the strong collective light–matter coupling regime to be reached with molecular materials. Pioneering works ...in this direction have shown the effects of this regime in the excited state reactivity of molecular systems and at the same time have opened up the question of whether it is possible to introduce any modifications in the electronic ground energy landscape which could affect chemical thermodynamics and/or kinetics. In this work, we use a model system of many molecules coupled to a surface-plasmon field to gain insight on the key parameters which govern the modifications of the ground-state potential energy surface. Our findings confirm that the energetic changes per molecule are determined by effects that are essentially on the order of single-molecule light–matter couplings, in contrast with those of the electronically excited states, for which energetic corrections are of a collective nature. Hence the prospects of ultrastrong coupling to change ground-state chemical reactions for the parameters studied in this model are limited. Still, we reveal some intriguing quantum-coherent effects associated with pathways of concerted reactions, where two or more molecules undergo reactions simultaneously and which can be of relevance in low-barrier reactions. Finally, we also explore modifications to nonadiabatic dynamics and conclude that, for our particular model, the presence of a large number of dark states yields negligible effects. Our study reveals new possibilities as well as limitations for the emerging field of polariton chemistry.
O objetivo do presente estudo foi de caracterizar a trajetória evolutiva do Brasil durante a participação dos Jogos Paralímpicos de Verão entre 1976-2020 e comparar com os países mais bem ranqueados ...nos Jogos Paralímpicos Rio 2016, buscando relacionar com o contexto histórico-político nacional e o plano estratégico do Comitê Paralímpico Brasileiro nos diferentes ciclos Paralímpicos. Até os Jogos Paralímpicos realizados em 2020, a delegação brasileira foi representada por um total de 774 atletas, sendo 251 medalhistas (70,9% homens; 29,1% mulheres) em 17 diferentes modalidades, quatro coletivas e treze individuais. Com relação ao tipo de deficiência, 64,9% dos atletas medalhistas apresentam deficiência física, 32,3% correspondem à deficiência visual e 2,8%, deficiência intelectual. Durante o período analisado, o Brasil conquistou 373 medalhas em participações, sendo 109 de ouro (29,2%), 132 de prata (35,4%) e 132 de bronze (35,4%). A modo conclusão, é possível destacar o avanço nas políticas públicas, plano estratégico e investimentos que favoreceram que nos últimos quatro ciclos paralímpicos, o Brasil pudesse se consolidar entre as 10 maiores potências mundiais paralímpicas, conquistando o maior número de medalhas em 2016 e o terceiro lugar no crescimento acumulado (3,2%) nos Jogos Paralímpicos de Verão entre 1988-2020, sendo superado apenas por China e Ucrânia.
Dendrimers up to the fourth generation were successfully prepared via the divergent growth strategy using a combination of thiol-ene “click” chemistry and traditional esterification reactions. The ...thiol-ene reactions were conducted under solvent-free, ambient conditions at room temperature by irradiating with UV light. The fourth-generation dendrimers were subsequently functionalized with carboxylic acid, pyrene, and Fmoc-protected cysteine moieties via thiol-ene reactions.
The genomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) worldwide are publicly available and are derived from studies due to the increase in the number of cases. The ...importance of study of mutations is related to the possible virulence and diagnosis of SARS‐CoV‐2. To identify circulating mutations present in SARS‐CoV‐2 genomic sequences in Mexico, Belize, and Guatemala to find out if the same strain spread to the south, and analyze the specificity of the primers used for diagnosis in these samples. Twenty three complete SARS‐CoV‐2 genomic sequences, available in the GISAID database from May 8 to September 11, 2020 were analyzed and aligned versus the genomic sequence reported in Wuhan, China (NC_045512.2), using Clustal Omega. Open reading frames were translated using the ExPASy Translate Tool and UCSF Chimera (v.1.12) for amino acid substitutions analysis. Finally, the sequences were aligned versus primers used in the diagnosis of COVID‐19. One hundred and eighty seven distinct variants were identified, of which 102 are missense, 66 synonymous and 19 noncoding. P4715L and P5828L substitutions in replicase polyprotein were found, as well as D614G in spike protein and L84S in ORF8 in Mexico, Belize, and Guatemala. The primers design by CDC of United States showed a positive E value. The genomic sequences of SARS‐CoV‐2 in Mexico, Belize, and Guatemala present similar mutations related to a virulent strain of greater infectivity, which could mean a greater capacity for inclusion in the host genome and be related to an increased spread of the virus in these countries, furthermore, its diagnosis would be affected.
Levels of variability and rates of adaptive evolution may be affected by hitchhiking, the effect of selection on evolution at linked sites. Hitchhiking can be caused either by "selective sweeps" or ...by background selection, involving the spread of new favorable alleles or the elimination of deleterious mutations, respectively. Recent analyses of population genomic data have fitted models where both these processes act simultaneously, to infer the parameters of selection. Here, we investigate the consequences of relaxing a key assumption of some of these studies, that the time occupied by a selective sweep is negligible compared with the neutral coalescent time. We derive a new expression for the expected level of neutral variability in the presence of recurrent selective sweeps and background selection. We also derive approximate integral expressions for the effects of recurrent selective sweeps. The accuracy of the theoretical predictions was tested against multilocus simulations, with selection, recombination, and mutation parameters that are realistic for
In the presence of crossing over, there is approximate agreement between the theoretical and simulation results. We show that the observed relationships between the rate of crossing over, and the level of synonymous site diversity and rate of adaptive evolution in
are probably mainly caused by background selection, whereas selective sweeps and population size changes are needed to produce the observed distortions of the site frequency spectrum.
Proteins are constantly undergoing folding and unfolding transitions, with rates that determine their homeostasis in vivo and modulate their biological function. The ability to optimize these rates ...without affecting overall native stability is hence highly desirable for protein engineering and design. The great challenge is, however, that mutations generally affect folding and unfolding rates with inversely complementary fractions of the net free energy change they inflict on the native state. Here we address this challenge by targeting the folding transition state (FTS) of chymotrypsin inhibitor 2 (CI2), a very slow and stable two‐state folding protein with an FTS known to be refractory to change by mutation. We first discovered that the CI2's FTS is energetically taxed by the desolvation of several, highly conserved, charges that form a buried salt bridge network in the native structure. Based on these findings, we designed a CI2 variant that bears just four mutations and aims to selectively stabilize the FTS. This variant has >250‐fold faster rates in both directions and hence identical native stability, demonstrating the success of our FTS‐centric design strategy. With an optimized FTS, CI2 also becomes 250‐fold more sensitive to proteolytic degradation by its natural substrate chymotrypsin, and completely loses its activity as inhibitor. These results indicate that CI2 has been selected through evolution to have a very unstable FTS in order to attain the kinetic stability needed to effectively function as protease inhibitor. Moreover, the CI2 case showcases that protein (un)folding rates can critically pivot around a few key residues‐interactions, which can strongly modify the general effects of known structural factors such as domain size and fold topology. From a practical standpoint, our results suggest that future efforts should perhaps focus on identifying such critical residues‐interactions in proteins as best strategy to significantly improve our ability to predict and engineer protein (un)folding rates.
Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. ...The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3–6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3′-dione were found altered in PRE, and their levels returned to those of a baseline control group 3–6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.
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