Kidney Injury after Cardiac Surgery: Prevention-Associated Cost Reduction.

INTRODUCTION: Cardiac surgery may induce acute kidney injury and the need for renal replacement therapy. It is also associated with higher hospital costs, morbidity and mortality. The aims of this study were to investigate predictors of cardiac surgery associated acute kidney injury in our population and to determine the burden of acute kidney injury in elective cardiac surgery, evaluating the potential cost effectiveness of preventing it through the application of the Kidney Disease: Improving Global Outcomes bundle of care to high-risk patient groups identified by the [TIMP-2]x[IGFBP7] used as a screening test. MATERIAL AND METHODS: In a University Hospital single-center retrospective cohort study we analyzed a consecutive sample of adults who underwent elective cardiac surgery between January and March 2015. A total of 276 patients were admitted during the study period. Data from all patients was analyzed until hospital discharge or the patient's death. The economic analysis was performed from the hospital costs' perspective. RESULTS: Cardiac surgery associated acute kidney injury occurred in 86 patients (31%). After adjustment, higher preoperative serum creatinine (mg/L, ORadj = 1.09; 95% CI: 1.01 - 1.17), lower preoperative hemoglobin (g/dL, ORadj = 0.79; 95% CI: 0.67 - 0.94), chronic systemic hypertension (ORadj = 5.00; 95% CI: 1.67 - 15.02), an increase in cardiopulmonary bypass time (min, ORadj = 1.01; 95% CI: 1.00 - 1.01) and perioperative use of sodium nitroprusside (ORadj = 6.33; 95% CI: 1.80 - 22.28) remained significantly associated with cardiac surgery related acute kidney injury. The expected cumulative surplus cost for the hospital linked with cardiac surgery associated acute kidney injury (86 patients) was €120 695.84. Based on a median absolute risk reduction of 16.6%, by dosing kidney damage biomarkers in every patient and using preventive measures in high-risk patients, we would expect a break-even point upon screening 78 patients, which would translate, in our patient cohort, into an overall cost benefit of €7145. CONCLUSION: Preoperative hemoglobin, serum creatinine, systemic hypertension, cardiopulmonary bypass time and perioperative use of sodium nitroprusside were independent predictors of cardiac surgery associated acute kidney injury. Our cost-effectiveness modelling suggests that the use of kidney structural damage biomarkers combined with an early prevention strategy could be associated with potential cost savings.

Cell Bank Origin of MDCK Parental Cells Shapes Adaptation to Serum-Free Suspension Culture and Canine Adenoviral Vector Production.

Phenotypic variation in cultured mammalian cell lines is known to be induced by passaging and culture conditions. Yet, the effect these variations have on the production of viral vectors has been overlooked. In this work we evaluated the impact of using Madin-Darby canine kidney (MDCK) parental cells from American Type Culture Collection (ATCC) or European Collection of Authenticated Cell Cultures (ECACC) cell bank repositories in both adherent and suspension cultures for the production of canine adenoviral vectors type 2 (CAV-2). To further explore the differences between cells, we conducted whole-genome transcriptome analysis. ECACC's MDCK showed to be a less heterogeneous population, more difficult to adapt to suspension and serum-free culture conditions, but more permissive to CAV-2 replication progression, enabling higher yields. Transcriptome data indicated that this increased permissiveness is due to a general down-regulation of biological networks of innate immunity in ECACC cells, including apoptosis and death receptor signaling, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling, toll-like receptors signaling and the canonical pathway of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. These results show the impact of MDCK source on the outcome of viral-based production processes further elucidating transcriptome signatures underlying enhanced adenoviral replication. Following functional validation, the genes and networks identified herein can be targeted in future engineering approaches aiming at improving the production of CAV-2 gene therapy vectors.

Year-Long Rhinovirus Infection is Influenced by Atmospheric Conditions, Outdoor Air Virus Presence, and Immune System-Related Genetic Polymorphisms.

Rhinovirus is a common picornavirus with over 150 serotypes and three species, which is responsible for half of the human common cold cases. In people with chronic respiratory conditions and elders, it may also cause life-threatening diseases. Transmission routes are not definitively established but may involve direct human-to-human and indirect transmission (surfaces and aerosols based). In the present study, year-long presence of virus was tested by qPCR in the nostrils of young healthy volunteers and indoor and outdoor air samples. Results were correlated to atmospheric conditions (meteorological and air quality parameters) and voluntaries immune system-related genetic polymorphisms (TOLLIP rs5743899, IL6 rs1800795, IL1B rs16944, TNFA rs1800629) typed by PCR-RFLP. Nasal samples showed increased frequency and viral titers of Rhinovirus in spring and autumn. No indoor air samples tested positive for Rhinovirus, whereas outdoor air samples tested positive in late autumn. Sun radiation, atmospheric SO2, and benzene levels correlated with nostrils Rhinovirus detection. Both IL6 and TOLLIP polymorphisms but not TNFA or IL1B influenced Rhinovirus detection in the nostrils of voluntaries. Taken together, the results indicate that Rhinovirus circulation is determined by environmental conditions (weather, air-borne virus, and air pollution) and genetically encoded individual variation in immunity.

Giant cell arteritis: Current treatment and management.

Glucocorticoids remain the cornerstone of medical therapy in giant cell arteritis (GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Imaging techniques (e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with large-vessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.

Contribuições da gestão de recursos humanos para a criatividade e inovação organizacional / Contributions of human resources management to organizational creativity and innovation

Inovar é, hoje, um imperativo para as organizações. Desse modo, é importante promover a criatividade dos colaboradores e apoiar o processo que a transforma em inovação. O objetivo desta pesquisa foi compreender como a Gestão de Recursos Humanos (GRH) pode promover um ambiente de trabalho propício à criatividade, na perspectiva dos colaboradores. Para isso, realizou-se um estudo de caso exploratório em uma empresa portuguesa de médio porte da área das Tecnologias de Informação (TI). Recorreu-se a diferentes fontes de análise, como observação participante, documentos organizacionais e entrevistas. Os dados resultantes dessas fontes foram analisados e organizados com ajuda da template analysis. Os resultados revelaram que, para as chefias e colaborador entrevistados, a criatividade na organização pode ser promovida por meio da existência de suporte para as novas ideias, tolerância ao erro, autonomia, liberdade para que os colaboradores exerçam suas funções e debates para a partilha de ideias. A GRH pode criar condições, por meio das suas práticas (p. ex., formação, avaliação de desempenho, recrutamento e seleção), para a promoção da criatividade e inovação organizacional.

Innovation is a key factor to organizations' competitiveness. To achieve that, it is important to promote creativity among employees and support the transformational process from creativity to innovation. The main objective of this research was to understand how Human Resource Management (HRM) can promote a work environment favorable to creativity, from the perspective of the employees. A case study was carried out on a medium-sized Portuguese information technology (IT) enterprise. Various research techniques were used to collect data, including observation, document analysis, and interviews. Data were organized and analyzed using a template analysis. The results revealed that, for the respondents (managers and employee), creativity within the organization can be promoted by the existence of support for new ideas, error tolerance, autonomy, freedom for employees to perform their tasks, and discussions to share ideas. HRM can create conditions, through their practices (e.g., training, performance evaluation, recruitment, and selection), to promote organizational creativity and innovation.

Contribuições da gestão de recursos humanos para a criatividade e inovação organizacional / Contributions of human resources management to organizational creativity and innovation

Inovar é, hoje, um imperativo para as organizações. Desse modo, é importante promover a criatividade dos colaboradores e apoiar o processo que a transforma em inovação. O objetivo desta pesquisa foi compreender como a Gestão de Recursos Humanos (GRH) pode promover um ambiente de trabalho propício à criatividade, na perspectiva dos colaboradores. Para isso, realizou-se um estudo de caso exploratório em uma empresa portuguesa de médio porte da área das Tecnologias de Informação (TI). Recorreu-se a diferentes fontes de análise, como observação participante, documentos organizacionais e entrevistas. Os dados resultantes dessas fontes foram analisados e organizados com ajuda da template analysis. Os resultados revelaram que, para as chefias e colaborador entrevistados, a criatividade na organização pode ser promovida por meio da existência de suporte para as novas ideias, tolerância ao erro, autonomia, liberdade para que os colaboradores exerçam suas funções e debates para a partilha de ideias. A GRH pode criar condições, por meio das suas práticas (p. ex., formação, avaliação de desempenho, recrutamento e seleção), para a promoção da criatividade e inovação organizacional.(AU)

Innovation is a key factor to organizations' competitiveness. To achieve that, it is important to promote creativity among employees and support the transformational process from creativity to innovation. The main objective of this research was to understand how Human Resource Management (HRM) can promote a work environment favorable to creativity, from the perspective of the employees. A case study was carried out on a medium-sized Portuguese information technology (IT) enterprise. Various research techniques were used to collect data, including observation, document analysis, and interviews. Data were organized and analyzed using a template analysis. The results revealed that, for the respondents (managers and employee), creativity within the organization can be promoted by the existence of support for new ideas, error tolerance, autonomy, freedom for employees to perform their tasks, and discussions to share ideas. HRM can create conditions, through their practices (e.g., training, performance evaluation, recruitment, and selection), to promote organizational creativity and innovation.(AU)

Stabilization of gammaretroviral and lentiviral vectors: from production to gene transfer.

BACKGROUND: The low stability of gammaretroviral and lentiviral vectors affects their production, making high quality clinical preparations a difficult goal to achieve. Recently, our laboratory has shown that the main inactivation mechanism for both these vectors is the loss of their capacity to perform reverse transcription. The present study aimed to increase the stability of gammaretroviral and lentiviral at 37 degrees C and at 4 degrees C. METHODS: Inactivation studies were performed with gammaretroviral and lentiviral vectors at 37 and 4 degrees C, with and without several stabilizing compounds. The residual viral infectivity and reverse transcription capacity of these samples were tested. RESULTS: The results obtained demonstrate that it is possible to increase the stability of reverse transcription and the infectivity stability of purified gammaretroviral vectors by adding recombinant human albumin (rHSA) to the storage buffer, both at 37 degrees C and at 4 degrees C. For lentiviral vectors, it was observed that further protection was needed. This was achieved by adding lipids to the storage buffer, using a mixture of lipoproteins and rHSA. The difference of stabilization between gammaretroviral and lentiviral vectors was validated by performing stabilization tests with vectors possessing different envelope proteins and produced by different cell lines. CONCLUSIONS: The presented study reveals that it is possible to increase the half-life of purified gammaretroviral and lentiviral vectors at 37 degrees C and at 4 degrees C, but the two vectors have different stabilization requirements: for retroviral vectors, the addition of rHSA is enough and, for lentiviral vectors, it is necessary to add both lipoproteins and rHSA. The increase of the stability of the reverse transcription process was shown to have a high impact with respect to the increase of the stability of infectivity.