Sputum Glucose and Glycemic Control in Cystic Fibrosis-Related Diabetes: A Cross-Sectional Study

Cystic fibrosis-related diabetes affects up to half of cystic fibrosis patients and is associated with increased mortality and more frequent pulmonary exacerbations. However, it is unclear to what degree good glycemic control might mitigate these risks and clinical outcomes have not previously been studied in relation to glucose from the lower airways, the site of infection and CF disease progression. We initially hypothesized that diabetic cystic fibrosis patients with glycosylated hemoglobin (HbA_(1c)) > 6.5% have worse pulmonary function, longer and more frequent exacerbations and also higher sputum glucose levels than patients with HbA_(1c) ≤ 6.5% or cystic fibrosis patients without diabetes. To test this, we analyzed spontaneously expectorated sputum samples from 88 cystic fibrosis patients. The median sputum glucose concentration was 0.70 mM (mean, 4.75 mM; range, 0-64.6 mM). Sputum glucose was not correlated with age, sex, body mass index, diabetes diagnosis, glycemic control, exacerbation frequency or length, or pulmonary function. Surprisingly, sputum glucose was highest in subjects with normal glucose tolerance, suggesting the dynamics of glycemic control, sputum glucose and pulmonary infections are more complex than previously thought. Two-year mean HbA_(1c) was positively correlated with the length of exacerbation admission (p 6.5% were hospitalized on average 6 days longer than those with HbA_(1c) ≤ 6.5% (p < 0.01). Current clinical care guidelines for cystic fibrosis-related diabetes target HbA_(1c) ≤ 7% to limit long-term microvascular damage, but more stringent glycemic control (HbA_(1c) ≤ 6.5%) may further reduce the short-term pulmonary complications

Isolation of Unknown Genes from Human Bone Marrow by Differental Screening and Single-Pass cDNA Sequences Determination

A cDNA sequencing project was initiated to characterize gene expression in human bone marrow and develop strategies to isolate novel genes. Forty-eight random cDNAs from total human bone marrow were subjected to single-pass DNA sequence analysis to determine a limited complexity of mRNAs expressed in the bone marrow. Overall, 8 cDNAs (17%) showed no similarity to known sequences. Information from DNA sequence analysis was used to develop a differential prescreen to subtract unwanted cDNAs and to enrich for unknown cDNAs. Forty-eight cDNAs that were negative with a complex probe were subject to single-pass DNA sequence determination. Of these prescreened cDNAs, the number of unknown sequences increased to 23 (48%). Unknown cDNAs were also characterized by RNA expression analysis using 25 different human leukemic cell lines. Of 13 unknown cDNAs tested, 10 were expressed in all cell types tested and 3 revealed a hematopoietic lineage-restricted expression pattern. Interestingly, while a total of only 96 bone marrow cDNAs were sequenced, 31 of these cDNAs represent sequences from unknown genes and 12 showed significant similarities to sequences in the data bases. One cDNA revealed a significant similarity to a serine/threonine-protein kinase at the amino acid level (56% identity for 123 amino acids) and may represent a previously unknown kinase. Differential screening techniques coupled with single-pass cDNA sequence analysis may prove to be a powerful and simple technique to examine developmental gene expression

Autophagy generates citrullinated peptides in human synoviocytes: a possible trigger for anti-citrullinated peptide antibodies

OBJECTIVES: Autophagy may represent a functional processing event that creates a substrate for autoreactivity. In particular, autophagy may play a role in the pathogenesis of RA, since autophagy is a key cellular event involved in the generation of citrullinated peptides, with consequent breakage of tolerance. Thus, in RA, autophagy may be the common feature in several situations (including smoking, joint injury and infection) that may drive the adaptive responses to citrullinated self-proteins. The aim of this study was the analysis, in vitro, of the role of autophagy in the generation of citrullinated peptides and, in vivo, of the relationship between autophagy and the production of anti-CCP antibodies (Abs). METHODS: For autophagy induction, fibroblast-like synoviocytes, primary fibroblasts and monocytes were stimulated with tunicamycin or rapamycin. Peptidyl arginine deiminase activity was tested by enzyme-linked immunosorbent assay, and protein citrullination was evaluated by western blotting. The main citrullinated RA candidate antigens, vimentin, α-enolase and filaggrin, were demonstrated by immunoprecipitation. The relationship between autophagy and anti-CCP Abs was analysed in 30 early-active RA patients. RESULTS: Our results demonstrated in vitro a role for autophagy in the citrullination process. Cells treated with tunicamycin or rapamycin showed peptidyl arginine deiminase 4 activation, with consequent protein citrullination. Immunoblotting and immunoprecipitation experiments, using specific Abs, identified the main citrullinated proteins: vimentin, α-enolase and filaggrin. In vivo, a significant association between levels of autophagy and anti-CCP Abs was observed in treatment-naïve early-active RA patients. CONCLUSION: These findings support the view that the processing of proteins in autophagy generates citrullinated peptides recognized by the immune system in RA

An Analytical Framework for Miles and Snow Typology and Dynamic Capabilities

The literature on dynamic capabilities is confusing, full of overlapping definitions, and contradictions. The theoretical and practical importance of developing and applying dynamic capabilities to sustain competitive advantage in complex external environment is central in studies about strategy nowadays. In this paper, we offer a definition of dynamic capabilities under two aspects: first, it refers to the shifting character of the environment; second, it emphasizes the key role of strategic management in appropriately adapting, integrating, and re-configuring internal and external organizational skills, resources, and functional competences towards a changing environment. This paper aims to clarify the concept of dynamic capabilities, propose an analytical framework that connects this “new” concept to a well known and recognized generic strategic model (Miles and Snow, 1978) and to the concept of sustainable competitive advantage and evolutionary fit. DOI:10.5585/riae.v13i1.193

Strategic Choice and Relational Dynamic Capabilities in a Brazilian Hotel Chain

The aim of this paper was to propose integration between two concepts: strategic choice and relational dynamic capability. For this purpose, the context of hotel business sector was chosen, due to its intensity and a need for formal and informal relationships. The research was divided in two stages: a survey, with a sample of 117 hotels in the State of Paraná and a case study. According to the findings, strategic typology determines a set of choices and behaviors resulting in different relationships. The aim of this paper was to propose integration between two concepts: strategic choice and relational dynamic capability. For this purpose, the context of hotel business sector was chosen, due to its intensity and a need for formal and informal relationships. The research was divided in two stages: a survey, with a sample of 117 hotels in the State of Paraná and a case study. According to the findings, strategic typology determines a set of choices and behaviors resulting in different relationships

Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum

Effective treatment for chronic infections is undermined by a significant gap in understanding of the physiological state of pathogens at the site of infection. Chronic pulmonary infections are responsible for the morbidity and mortality of millions of immunocompromised individuals worldwide, yet drugs that are successful in laboratory culture are far less effective against pathogen populations persisting in vivo. Laboratory models, upon which preclinical development of new drugs is based, can only replicate host conditions when we understand the metabolic state of the pathogens and the degree of heterogeneity within the population. In this study, we measured the anabolic activity of the pathogen Staphylococcus aureus directly in the sputum of pediatric patients with cystic fibrosis (CF), by combining the high sensitivity of isotope ratio mass spectrometry with a heavy water labeling approach to capture the full range of in situ growth rates. Our results reveal S. aureus generation times with a median of 2.1 d, with extensive growth rate heterogeneity at the single-cell level. These growth rates are far below the detection limit of previous estimates of CF pathogen growth rates, and the rates are slowest in acutely sick patients undergoing pulmonary exacerbations; nevertheless, they are accessible to experimental replication within laboratory models. Treatment regimens that include specific antibiotics (vancomycin, piperacillin/tazobactam, tobramycin) further appear to correlate with slow growth of S. aureus on average, but follow-up longitudinal studies must be performed to determine whether this effect holds for individual patients

Sustainability indicators in the agroforestry systems of family farmers in the district of Tomé-Açu, Pará

The aim of this article was to evaluate, using sustainability indicators, agroforestry systems (AFS) on the properties of family farmers in the district of Tomé-Açu, Pará, arising from the transition processes of different production systems. Eight AFS, three areas of secondary vegetation, and three conventional systems were evaluated. Direct observation was used to evaluate the sustainability indicators, assigning a value from 1 to 10 to each indicator (1 - undesirable; 5 - moderate and 10 - ideal). The mean value of the indicators was determined for each system under evaluation. The areas under conventional systems had the lowest value, of 0.25 for the crop-health indicators and 1.32 for soil quality, which suggests the need for proper management to prevent environmental problems in areas of pasture, cleared land and monocropped black pepper. The highest values of 4.1 for the crop-health indicators and 6.99 for soil quality, were obtained in the areas of secondary vegetation, and values of 3.0 for crop health and 6.1 for soil quality in the areas of AFS-BP, emphasising the role of secondary vegetation and agroforestry systems in recovering the productive potential of agrosystems. It can be concluded that the use of a simple technique (radar charts) together with statistical methods show that secondary vegetation, agroforestry and conventional systems differ; however, secondary vegetation and AFS are more sustainable, as they showed better results for each of the indicators under evaluation compared to the conventional systems

O processo de terceirização de serviços hoteleiros: Motivações e fundamentos teóricos

This study discusses the process of outsourcing in hotels. The aim of this study was to determine why the hotels outsource their services and activities, and how the outsourcing process occurs in hotels in Curitiba, in the perspective of dynamic capabilities. Specifically we took as basis the theoretical model of Teece (2007) of the microfoundations of dynamic capabilities, in which the author proposes that the exploitation of organizational boundaries and coespecialization are part of the dynamic capability of organizations. Regarding the analysis, we used the technique of analyzing the content of categorical six hotels. The results show that the decisions of outsourcing were primarily motivated by financial reasons, such as the possibility of reducing costs and improving performance financier. In relation to the outsourcing decision process, it was observed that formalized processes are adopted especially by hotels that belong to chains. Independent hotels adopt more informal processes in the outsourcing decision.Este estudio analiza el proceso de externalización en los hoteles. El objetivo de este estudio fue determinar por qué los hoteles externalizar sus servicios y actividades, y cómo el proceso de externalización se produce en los hoteles en Curitiba, en la perspectiva de las capacidades dinámicas. En concreto, se tomó como base el modelo teórico de Teece (2007) de los microfundamentos de las capacidades dinámicas, en las que el autor propone que la explotación de los límites de la organización y coespecialization son parte de la capacidad dinámica de las organizaciones. En cuanto al análisis, se utilizó la técnica de análisis del contenido de categóricos seis hoteles. Los resultados muestran que las decisiones de externalización fueron motivados principalmente por razones financieras, tales como la posibilidad de reducir los costos y mejorar el rendimiento financiero. En relación con el proceso de toma externa, se observó que se adoptó procesos formalizados especialmente por hoteles que pertenecen a cadenas. Hoteles Independent adoptar procesos más informales en la decisión de outsourcing.Este estudo discute o processo de terceirização em hotéis. O objetivo deste estudo foi verificar por que os hotéis terceirizam seus serviços e atividades, e como ocorre o processo de terceirização nos hotéis em Curitiba, na perspectiva das capacidades dinâmicas. Especificamente tomou-se como base o modelo teórico de Teece (2007) das microfundações das capacidades dinâmicas, na qual o autor propõe que a exploração dos limites organizacionais e a coespecialização fazem parte da capacidade dinâmica das organizações. Quanto à análise, utilizou-se a técnica da análise de conteúdo do tipo categorial em seis hotéis. Os resultados mostram que as decisões das terceirizações foram motivadas principalmente por razões financeiras, tais como a possibilidade de redução de custos e a melhoria do desempenho financeiro.Com relação ao processo de decisão da terceirização, observou-se que processos formalizados são adotados especialmente por hotéis pertencentes a redes. Hotéis independentes adotam processos mais informais na decisão da terceirização

Solute Transporter OCTN1/Slc22a4 Affects Disease Severity and Response to Infliximab in Experimental Colitis: Role of Gut Microbiota and Immune Modulation

Background Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis.Methods A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively.Results Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells.Conclusions Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies.In this article, we evaluated the role of OCTN1, an organic cation transporter, in modifying gut microbiota and immune T cell populations, as well as its effects on experimental colitis and the response to infliximab treatment

Desenvolvimento de preparações com adição de pescado e aproveitamento integral de alimentos para a alimentação escolar

Na alimentação escolar existem ainda poucas preparações que utiliza a Carne Mecanicamente Separada (CMS) de pescado e o aproveitamento integral de alimentos. Diante disso, o objetivo do presente artigo foi elaborar preparações acrescidas de CMS de pescado juntamente com o aproveitamento integral de alimentos para serem inseridas na alimentação escolar. Foram elaboradas fichas técnicas de preparo das receitas, a fim de obter informações sobre custo e rendimento das preparações desenvolvidas. A posteriori, foram realizadas análises direta, com amostras em triplicata, e indireta, nos quais os dados obtidos em laboratório foram comparados àqueles obtidos por meio das tabelas de composição utilizadas: FRANCO (2007), TACO (2011) e IBGE (2011). Os resultados mostraram que houve divergência entre os indicadores obtidos por meio da análise direta e aqueles da análise indireta, demonstrando também que as preparações desenvolvidas são viáveis do ponto de vista nutricional para serem inseridas na alimentação escolar