The intracellular Ig fold: a robust protein scaffold for the engineering of molecular recognition

Protein scaffolds that support molecular recognition have multiple applications in biotechnology. Thus, protein frames with robust structural cores but adaptable surface loops are in continued demand. Recently, notable progress has been made in the characterization of Ig domains of intracellular origin—in particular, modular components of the titin myofilament. These Ig belong to the I(intermediate)-type, are remarkably stable, highly soluble and undemanding to produce in the cytoplasm of Escherichia coli. Using the Z1 domain from titin as representative, we show that the I-Ig fold tolerates the drastic diversification of its CD loop, constituting an effective peptide display system. We examine the stability of CD-loop-grafted Z1-peptide chimeras using differential scanning fluorimetry, Fourier transform infrared spectroscopy and nuclear magnetic resonance and demonstrate that the introduction of bioreactive affinity binders in this position does not compromise the structural integrity of the domain. Further, the binding efficiency of the exogenous peptide sequences in Z1 is analyzed using pull-down assays and isothermal titration calorimetry. We show that an internally grafted, affinity FLAG tag is functional within the context of the fold, interacting with the anti-FLAG M2 antibody in solution and in affinity gel. Together, these data reveal the potential of the intracellular Ig scaffold for targeted functionalizatio

Factors associated with nurses' positive attitudes towards families' involvement in nursing care: a scoping review

Aim: to map the factors associated with nurses’ positive attitudes towards families’ involvement in nursing care and to identify any existing gaps in knowledge. Background: several tools have been proposed to assess the attitudes, beliefs and practices of nurses towards families in different care contexts. However, there is a knowledge gap on how the results of these tools can identify the factors that are associated with more positive attitudes of nurses. Design: a scoping review based on the steps proposed by the Joanna Briggs Institute. Methods: three independent reviewers searched the databases: PUBMED/Medline; LILACS; Virtual Health Library; PsycInfo; Google Scholar; SCOPUS and CINAHL, from 2006 to August 2021, guided by the question: what are the factors associated with nurses’ positive attitudes towards families´ involvement in nursing care, in studies that used one or both of the following two scales ‘Families’ Importance in Nursing Care- Nurses’ Attitudes’ and ‘Family Nursing Practice Scale’? This review was conducted in accordance with PRISMA-ScR. Results: twenty-six primary studies were identified, in which 9,620 nurses participated. Positive attitudes were associated with three types of variables: (a) personal— longer working career (42.3%) and older age (26.9%); (b) educational—higher level of academic education (30.8%) and family nursing education (23.0%); and (c) workplace— working in primary health care and/or outpatient clinics (34.6%) or in a unit with philosophy/approach to families (23.0%). Conclusions: personal variables such as age and time of service are non-modifiable aspects, but educational and workplace variables are subject to intervention to improve nurses’ attitudes towards families’ involvement in nursing care. Continuing development programmes about family care can constitute important strategies to improve positive attitudes of nurses towards families in practice. Relevance to clinical practice: recognising the characteristics associated with nurses´ positive attitudes towards families may enable the development of tailored interventions that promote family-focused care

La equidad en el gasto público en salud

El objetivo de esta investigación es abordar el tema de la "equidad" en el acceso a bienes y servicios de salud provistos por el sector público en la provincia de Buenos Aires, como una medida de su desempeño y, en línea con la temática planteada emprender el análisis de desigualdad en la distribución del gasto público en salud.Departamento de Economí

The inclusion of primary health care evaluation at the State level of the Brazilian National Health System by way of participatory teaching, learning and working practices

OBJETIVOS: desenvolver uma metodologia de intervenção e aplicá-la às equipes das Secretarias Estaduais de Saúde (SES) objetivando incorporar a prática de monitoramento e avaliação da atenção básica através de processo de capacitação e realização de atividade real de planejamento e programação em saúde. MÉTODOS: foi desenvolvido um processo de ensino-aprendizagem-trabalho que incorporou ao processo de capacitação uma atividade de planejamento em saúde. A qualidade dos dois processos é assegurada através do estabelecimento de princípios e critérios para a organização da capacitação, para a elaboração da proposta metodológica de monitoramento e avaliação e para a condução didático-pedagógica do curso. RESULTADOS: a metodologia foi aplicada nos Estados de Mato Grosso do Sul (MS), Tocantins (TO) e Amazonas (AM), respeitando as particularidades locais em termos de organização da SES e da qualificação e capacidade dos técnicos responsáveis pela atenção básica. Foram produzidas propostas metodológicas estruturalmente semelhantes, mas diferentes nas suas prioridades e propostas de desenvolvimento. Dois anos após o término da intervenção, efeitos desse trabalho ainda estão sendo identificados. CONCLUSÕES: os resultados obtidos em MS, TO e AM revelam a capacidade que a abordagem baseada na tríade ensino-aprendizagem-trabalho possui para a institucionalização de novas práticas de trabalho nos serviços de saúde.OBJECTIVES: to develop an intervention methodology and apply it to the State Health Department teams, as a way of introducing monitoring and evaluation of primary health care by way of training and carrying out a real health planning activity. METHODS: learning and working practices were developed that included training and a health planning activity. The quality of both of these processes was ensured by establishing the principles and criteria for organizing training, drawing up a monitoring and evaluation methodology proposal and teaching practices. RESULTS: the methodology was applied in the Brazilian States of Mato Grosso do Sul (MS), Tocantins (TO) and Amazonas (AM), paying due respect to the specific features of each locality's State Health Department and the qualifications and training of technical staff responsible for primary health care. Methodological proposals were drawn up that were structurally similar but had differing priorities and development proposals. Two years after conclusion of this intervention, the effects could still be identified. CONCLUSIONS: the results obtained in MS, TO and AM reveal the capacity of an approach based on teaching, learning and work to introduce new working practices in health services throughout the institution

Asteroid target selection for the new Rosetta mission baseline: 21 Lutetia and 2867 Steins

Reproduced with permission. Copyright ESO. Article published by EDP Sciences and available at http://www.aanda.org.International audienceThe new Rosetta mission baseline to the comet 67P/Churyumov-Gerasimenko includes two asteroid fly-bys. To help in target selection we studied all the candidates of all the possible scenarios. Observations have been carried out at ESO-NTT (La Silla, Chile), TNG (Canaries), and NASA-IRTF (Hawaii) telescopes, in order to determine the taxonomy of all the candidates. The asteroid targets were chosen after the spacecraft interplanetary orbit insertion manoeuvre, when the available total amount of ΔV was known. On the basis of our analysis and the available of ΔV, we recommended to the ESA ScienceWorking Group the asteroids 21 Lutetia and 2867 Steins as targets for the Rosetta mission. The nature of Lutetia is still controversial. Lutetia's spectral properties may be consistent with a composition similar to carbonaceous chondrite meteorites. The spectral properties of Steins suggest a more extensive thermal history. Steins may have a composition similar to relatively rare enstatite chondrite/achondrite meteorites

analysis of pro arrhythmic effects induced by different routes of administration of bone marrow stem cells

There has been repeated concern that intramyocardial (i.m.) delivery of cells could cause ventricular arrhythmias. The aim of the study was to evaluate the pro-arrhythmic effects of bone marrow stem cell (BMSC) injection and compare different routes of administration. An ischemia reperfusion injury was induced in New Zealand rabbits by temporal ligation of anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection. We compared different routes of BMSC injections, intramyocardial (i.m.) versus intravenous (i.v.) administration of cells. A control group was treated with i.m. injections of saline. The hourly number of supra- and ventricular premature contractions (VPCs), QT interval time and QTc time were recorded and calculated. At Day 7 after cell injections, VPCs were more frequent in the groups treated with i.m. BMSCs and i.m. saline compared with i.v. BMSCs (132 ±19; 54±14 and 34±9, respectively; P<0.01 within groups), whereas at Day 21 the number of VPCs was higher in the 2 groups treated with either i.m. or i.v. BMSCs compared with saline (96±23; 52±19 and 25±20, respectively; P<0.001 within groups). QTc time interval was prolonged during ischemia, and recovered in control and in the group treated with i.v. cells, whereas it remained longer in rabbits treated with i.m. BMSCs. These findings show that i.m. BMSC injections induced a high number of pre-arrhythmic events suggesting changes in cardiac electrophysiological properties. The i.v. administration of cells resulted in lower VPC beats and in a temporary QT prolongation. These results suggest that the combination of BMS cells and i.m. injections induced an electrical remodeling that contributed to the development of arrhythmias

Untargeted metabolomics to go beyond the canonical effect of acetylsalicylic acid

15openInternationalItalian coauthor/editorGiven to its ability to irreversibly acetylate the platelet cyclooxygenase-1 enzyme, acetylsalicylic acid (ASA) is successfully employed for the prevention of cardiovascular disease. Recently, an antitumoral effect of ASA in colorectal cancer has been increasingly documented. However, the molecular and metabolic mechanisms by which ASA exerts such effect is largely unknown. Using a new, untargeted liquid chromatography–mass spectrometry approach, we have analyzed urine samples from seven healthy participants that each ingested 100 mg of ASA once daily for 1 week. Of the 2007 features detected, 25 metabolites differing after ASA ingestion (nominal p 1) were identified, and pathway analysis revealed low levels of glutamine and of metabolites involved in histidine and purine metabolisms. Likewise, consistent with an altered fatty acid β-oxidation process, a decrease in several short- and medium-chain acyl-carnitines was observed. An abnormal β-oxidation and a lower than normal glutamine availability suggests reduced synthesis of acetyl-Co-A, as they are events linked to one another and experimentally related to ASA antiproliferative effects. While giving an example of how untargeted metabolomics allows us to explore new clinical applications of drugs, the present data provide a direction to be pursued to test the therapeutic effects of ASA—e.g., the antitumoral effect—beyond cardiovascular protectionopenDi Minno, Alessandro; Porro, Benedetta; Turnu, Linda; Manega, Chiara Maria; Eligini, Sonia; Barbieri, Simone; Chiesa, Mattia; Poggio, Paolo; Squellerio, Isabella; Anesi, Andrea; Fiorelli, Susanna; Caruso, Donatella; Veglia, Fabrizio; Cavalca, Viviana; Tremoli, ElenaDi Minno, A.; Porro, B.; Turnu, L.; Manega, C.M.; Eligini, S.; Barbieri, S.; Chiesa, M.; Poggio, P.; Squellerio, I.; Anesi, A.; Fiorelli, S.; Caruso, D.; Veglia, F.; Cavalca, V.; Tremoli, E

Experience of women in labor with the use of flowers essences / Vivência de mulheres em trabalho de parto com o uso de essências florais

OBJETIVO: O estudo descreve a vivencia de mulheres submetidas ao uso de essências florais como terapia não farmacológica para o alivio da dor e ansiedade durante o trabalho de parto. MÉTODOS: Pesquisa descritiva exploratória, de conteúdo qualitativo, realizada com 30 parturientes, em um centro de parto normal público, intra-hospitalar da cidade de São Paulo. RESULTADOS: Constatou-se que os efeitos da terapia floral, atuaram em sinergia, na redução dos sintomas de estresse-medo-tensão, além do aumento do bem-estar emocional proporcionando às parturientes a oportunidade de protagonizar o seu próprio trabalho de parto e parto. CONCLUSÃO: Conclui-se que o uso da essência floral, no trabalho de parto, proporcionou calma, relaxamento, concentração e coragem às mulheres, emoções estas que possibilitaram melhor controle da dor e da ansiedade

Experience of women in labor with the use of flowers essences / Vivência de mulheres em trabalho de parto com o uso de essências florais

OBJETIVO: O estudo descreve a vivencia de mulheres submetidas ao uso de essências florais como terapia não farmacológica para o alivio da dor e ansiedade durante o trabalho de parto. MÉTODOS: Pesquisa descritiva exploratória, de conteúdo qualitativo, realizada com 30 parturientes, em um centro de parto normal público, intra-hospitalar da cidade de São Paulo. RESULTADOS: Constatou-se que os efeitos da terapia floral, atuaram em sinergia, na redução dos sintomas de estresse-medo-tensão, além do aumento do bem-estar emocional proporcionando às parturientes a oportunidade de protagonizar o seu próprio trabalho de parto e parto. CONCLUSÃO: Conclui-se que o uso da essência floral, no trabalho de parto, proporcionou calma, relaxamento, concentração e coragem às mulheres, emoções estas que possibilitaram melhor controle da dor e da ansiedade

Left atrial size is a potent predictor of mortality in mitral regurgitation due to flail leaflets results from a large international multicenter study

Background-Left atrium (LA) enlargement is common in organic mitral regurgitation (MR) and is an emerging prognostic indicator. However, outcome implications of LA enlargement have not been analyzed in the context of routine clinical practice and in a multicenter study. Methods and Results-The Mitral Regurgitation International DAtabase (MIDA) registry enrolls patients with organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US and European centers. We investigated the relation between LA diameter and mortality under medical treatment and after mitral surgery in 788 patients in sinus rhythm (64±12 years; median LA, 48 [43 to 52] mm). LA diameter was independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04 to 1.12] per 1 mm increment). Compared with patients with LA<55 mm, those with LA â¥55 mm had lower 8-year overall survival (P<0.001). LA â¥55 mm independently predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The association of LA â¥55 mm and mortality was consistent in subgroups. Similar excess mortality associated with LA â¥55 mm was observed in asymptomatic and symptomatic patients (P for interaction, 0.77). In patients who underwent mitral surgery, LA â¥55 mm had no impact on postoperative outcome (P<0.20). Mitral surgery was associated with greater survival benefit in patients with LA â¥55 mm compared with LA <55 mm (P for interaction, 0.008). Conclusions-In MR caused by flail leaflets, LA diameter â¥55 mm is associated with increased mortality under medical treatment, independent of the presence of symptoms or left ventricular dysfunction. © 2011 American Heart Association, Inc