Markers of small airway involvement and asthma control in moderate-to-severe asthmatic patients

SUMMARY Background: Involvement of small airways has been hypothesized to be responsible of poor asthma control in subgroups of patients, also due to the difficulty of inhaled drugs to reach peripheral airways. Aim: To evaluate in a sample of moderate-severe asthmatic patients under treatment with inhaled corticosteroid/long acting beta2-agonist (ICS/LABA) combinations, the relationship between asthma control, as assessed by traditional clinical, functional and biological findings, and some measurements of small airway involvement. Patients and methods: 31 asthmatic patients regularly treated with ICS/LABA combinations were evaluated for the level of asthma control according to GINA guidelines, by a 4-month period of diary card and peak expiratory flow (PEF) monitoring, FEV1 and exacerbation rate; sputum eosinophils and fractional exhaled nitric oxide (eNO50) were also measured. Small airway involvement was assessed by single breath nitrogen washout (CV, ΔN2%), alveolo-arterial O2 and arterial-alveolar CO2 gradients (AaDO2, aADCO2), and alveolar concentration of nitric oxide (CalvNO). Results: According to GINA guidelines, patients were defined as well controlled (N=10), partly controlled (N=11) and not controlled (N=10). No significant difference was observed among the groups as regards markers of small airway involvement, as well as for biomarkers. When well controlled and partly controlled were considered together, not controlled patients showed a significantly higher AaDO2 difference. A significant correlation was observed between AaDO2 and FEV1 %pred, sputum eosinophil percentage, and rescue medication use. Conclusions: Small airway involvement as assessed by AaDO2 may be observed in clinically not controlled moderate-severe asthmatics under ICS/LABA combination treatment, despite a not significant difference in FEV1 and airway biomarkers

Foreword

The Articles and Comments in this Volume cover a wide range of topics. Appropriately, each one uses a tiered attack on an international legal issue, making the authors\u27 expressed arguments tremendously strong. These articles represent the kind of international thinking that is and will be required of our intellectuals in the upcoming decades. I hope that the fresh, new ideas and original legal analysis of each piece in this Volume increase the number of levels and broaden the bandwidth in which we discuss every international legal issue to come

The Myth of the Full Ride : Cheating Our Collegiate Athletes and the Need for Additional NCAA Scholarship-Limit Reform

The National Collegiate Athletic Association should amend Bylaw 15.1 and allow institutions to award athletic scholarship monies up to the institutionally set, estimated cost of attendance. NCAA Bylaw 15.1 limits an individual student-athlete’s athletic scholarships and other financial aid based on athletic ability to the value of a full grant-in-aid. The individual student-athlete scholarship limit is an arbitrary price cap and an unreasonable restraint of trade in violation of section 1 of the Sherman Act because it prevents student-athletes from receiving financial aid up to the institutionally set, estimated cost of attendance, which includes the additional expenses an institution deems necessary to meet the cost of living at the school. Setting the permissible athletic scholarship limit at the institutionally set, estimated cost of attendance is a less restrictive alternative that still protects the pro-competitive virtues the NCAA has frequently proffered in support of its price cap. The NCAA has settled previous antitrust complaints brought by student-athletes alleging that athletic scholarship limits were unreasonable restraints of trade. And recently, the NCAA recognized that settlement was not enough to fulfill the NCAA’s educational mission and preserve the rights of student-athletes in Division I programs. But instead of retiring the deficient limit, the NCAA designated a new, arbitrary cap. However, the NCAA suspended implementation of this change so the Division I Board of Directors could reconsider the amendment. In reconsidering the amendment, and in light of the recent settlement in the White v. NCAA lawsuit, the NCAA should fully liberalize Bylaw 15.1 and allow institutions to award athletic scholarship monies up to the institutionally set, estimated cost of attendance. This is the only way to ensure that all future Division I student-athletes will not be financially disadvantaged even with the hard work these athletes perform for their institutions’ athletic programs; further, anything less is an unreasonable restraint of trade

L'accompagnamento nell'ultimo tratto di vita. Una riflessione etica a partire dal pensiero di Cicely Saunders

ItA partire dalle riflessioni di Cicely Saunders sul "morire" scopo del presente contributo è interrogare le difficoltà e le sfide che l'ultima parte della vita pone al pensiero al fine di delineare le modalità di un accompagnamento degno della e alla persona umana.EnStarting from Cicely Saunders' reflections on "dying", the purpose of this contribution is to question the troubles and challenges that the last part of life poses to thought in order to outline the ways of an accompaniment worthy of and to the human person

Estudo etnográfico no Festival de Percussão São Batuque 2015: os Toques do Terreiro nas oficinas de Gabi Guedes e Pai Carlos de Oxóssi

Esta comunicação apresenta o estudo etnográfico realizado em duas oficinas sobre o tema “Toques do Terreiro” realizadas no Festival Internacional de Percussão São Batuque 2015 em Brasília – DF. Através dos percussionistas e mestres tocadores do Candomblé de Ketu-Nagô, os ogãs Gabi Guedes e Pai Carlos de Oxóssi, foram abordados os aspectos musicais e a compreensão de alguns dos contextos religiosos empregados aos toques utilizados nos terreiros e rituais do Candomblé de Keto. Com o objetivo principal de iniciar os estudos etnográficos por meio dos primeiros contatos com os músicos dos terreiros, o presente trabalho realizado identificou que em dois diferentes locais, a Universidade de Brasília e a Casa de Cultura do Varjão, foram observadas diferentes metodologias de ensino-aprendizagem sobre o mesmo conteúdo, resultantes das diferentes faixas etárias e locais de realização das oficinas; e que estas metodologias possibilitaram aos participantes obterem duas formas de experiência: aural ou oral. Em um festival que objetivava fortalecer a cultura afro-brasileira e trazer para o público um resgate da identidade cultural nacional, muitos jovens foram beneficiados nestas oficinas por terem a oportunidade de adquirir novas experiências, vivenciando expressões culturais das quais não pertencem e que não tiveram contato anteriormente. Dessa forma, esta pesquisa descreve como foram realizados os trabalhos nas diferentes oficinas e apresenta as semelhanças, diferenças e conclusões obtidas através deste estudo etnográfico

Understanding the mechanism of recognition of gab2 by the N-SH2 domain of SHP2

Gab2 is a scaffold protein with a crucial role in colocalizing signaling proteins and it is involved in the regulation of several important molecular pathways. SHP2 is a protein phosphatase that binds, through its two SH2 domains, specific consensus sequences presenting a phosphorylated tyrosine located on the disordered tail of Gab2. To shed light on the details of such a fundamental interaction for the physiology of the cell, we present a complete mutational analysis of the kinetics of binding between the N-SH2 domain of SHP2 and a peptide mimicking a specific region of Gab2. By analyzing kinetic data, we determined structural features of the transition state of the N-SH2 domain binding to Gab2, highlighting a remarkable cooperativity of the binding reaction. Furthermore, comparison of these data with ones previously obtained for another SH2 domain suggests the presence of underlying general features characterizing the binding process of SH2 domains. Data are discussed under the light of previous works on SH2 domains

The kinetics of folding of the NSH2 domain from p85

SH2 domains are protein domains that mediate protein-protein interaction through the recognition and binding of specific sequences containing phosphorylated tyrosines. The p85 protein is the regulatory subunit of the heterodimeric enzyme PI3K, an important enzyme involved in several molecular pathways. In this work we characterize the folding kinetics of the NSH2 domain of p85. Our data clearly reveal peculiar folding kinetics, characterized by an apparent mismatch between the observed folding and unfolding kinetics. Taking advantage of double mixing stopped flow experiments and site directed mutagenesis we demonstrate that such behavior is due to the cis/trans isomerization of the peptide bond between D73 and P74, being in a cis conformation in the native protein. Our data are discussed in comparison with previous works on the folding of other SH2 domains

Experimental characterization of the interaction between the n-terminal sh3 domain of crkl and c3g

Crkl is a protein involved in the onset of several cancer pathologies that exerts its function only through its protein–protein interaction domains, a SH2 domain and two SH3 domains. SH3 domains are small protein interaction modules that mediate the binding and recognition of proline-rich sequences. One of the main physiological interactors of Crkl is C3G (also known as RAPGEF1), an interaction with key implications in regulating cellular growth and differentiation, cell morphogenesis and adhesion processes. Thus, understanding the interaction between Crkl and C3G is fundamental to gaining information about the molecular determinants of the several cancer pathologies in which these proteins are involved. In this paper, through a combination of fast kinetics at different experimental conditions and site-directed mutagenesis, we characterize the binding reaction between the N-SH3 domain of Crkl and a peptide mimicking a specific portion of C3G. Our results show a clear effect of pH on the stability of the complex, due to the protonation of negatively charged residues in the binding pocket of N-SH3. Our results are discussed under the light of previous work on SH3 domains