Data platforms for open life sciences-A systematic analysis of management instruments

Open data platforms are interfaces between data demand of and supply from their users. Yet, data platform providers frequently struggle to aggregate data to suit their users' needs and to establish a high intensity of data exchange in a collaborative environment. Here, using open life science data platforms as an example for a diverse data structure, we systematically categorize these platforms based on their technology intermediation and the range of domains they cover to derive general and specific success factors for their management instruments. Our qualitative content analysis is based on 39 in-depth interviews with experts employed by data platforms and external stakeholders. We thus complement peer initiatives which focus solely on data quality, by additionally highlighting the data platforms' role to enable data utilization for innovative output. Based on our analysis, we propose a clearly structured and detailed guideline for seven management instruments. This guideline helps to establish and operationalize data platforms and to best exploit the data provided. Our findings support further exploitation of the open innovation potential in the life sciences and beyond

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Spielen Statine eine Rolle als adjuvante Therapie bei Entzündung? / Do statins play a role as an adjuvant therapy in inflammation?

Despite recent advances in management of patients in intensive care units, sepsis and septic shock are the major causes of morbidity and mortality. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious material are the first-line therapy of choice. In addition, various immunomodulatory treatments have been investigated during the past decades. However, despite promising results in studies with animal models, studies in humans with antibodies against lipopolysaccharide (LPS), tumor necrosis factor and interleukin-1 have not been successful. In addition, high doses of steroids, immunoglobulins or antibodies against LPS and cytokines did not reduce mortality, probably owing to timing and dosage of these drugs. Prophylactic administration of immunomodulatory drugs cannot be recommended due to severe adverse effects. However, owing to pleiotropic effects of statins this class of cholesterol lowering drugs has been suggested to be beneficial as adjuvant therapy for sepsis. The present review summarizes the pathophysiology of sepsis as well as experimental and clinical evidence for the use of statins in sepsis.Trotz der Fortschritte der Medizin stellen schwere Entzündungsreaktionen wie die Sepsis eine wesentliche Ursache für Mortalität und Morbidität auf Intensivstationen dar. Zur kausalen Therapie gehört neben der Beseitigung der auslösenden Ursache durch chirurgische Maßnahmen vor allem eine effektive Antibiose. Weiterhin werden supportive Maßnahmen wie Kreislaufunterstützung, Nierenersatztherapie, Therapie von Gerinnungsstörungen und metabolischer Entgleisung zur Therapie eingesetzt. Darüber hinaus wurde in den vergangenen Jahren eine Vielzahl von immunomodulatorischen Therapien untersucht. Hierzu gehören neutralisierende Antikörper gegen Endotoxin oder proinflam-matorische Zytokine, Kortison, Immunglobuline und spezifische Gerinnungsinhibitoren. Neuere Studien weisen darauf hin, dass Statine (HMG-CoA-Reduktase-Inhibitoren) antientzündliche Wirkung haben und eine andauernde Statintherapie mit verminderter Inzidenz bakterieller Infektionen assoziiert ist. Aus diesem Grund wurden Statine als neue adjuvante Therpaie bei schweren Entzündungen und Sepsis vorgeschlagen. Im Gegensatz zu anderen antientzündlichen Therapien wäre hier auch ein prophylaktischer Einsatz bei Hochrisikopatienten, zum Beispiel vor elektiven chirurgischen Eingriffen, möglich. In der vorliegenden Arbeit sind die pathophysiologischen Grundlagen der Sepsis sowie die experimentelle Hintergründe und die ersten klinischen Daten zum Einsatz der Statine bei Sepsis zusammengefasst

Physicians' communication of risks from non-steroidal anti-inflammatory drugs and attitude towards providing adverse drug reaction information to patients

Rationale aims and objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for orthopaedic conditions, therefore this study aimed to explore orthopaedic physicians’ perceptions of their role in NSAID-risk communication, their attitudes towards the necessity of informing patients about adverse drug reactions (ADR), and factors associated with these. Methods Self-administered questionnaires were mailed to all 206 orthopaedic physicians working at hospitals in Northeastern Thailand. Attitudes were assessed using 17 statements and total scores classed as poor, moderate and good attitude. Results: Sixty-six questionnaires were returned (32.04%). The responses showed that 75% of physicians claimed to communicate NSAID ADR information, more frequently about gastrointestinal (GI) complications, than about renal and cardiovascular (CVS) complications. ADR management (36%) and monitoring (30%) were not frequently communicated. The time spent with patients was associated with provision of ADR and monitoring advice. Renal function was the risk factor of greatest concern for prescribing any NSAID, followed by history of GI complications, and allergy for non-selective NSAIDs, and history of CVS diseases and age for selective COX-2 NSAIDs. Most physicians (41) had moderate attitude towards providing information and 24 good attitude. Fewer physicians working in tertiary hospitals than general and community hospital physicians considered that time limitations prevented counseling and that patient information leaflets offered easily accessible information. Additionally, more physicians who did not inform patients about ADRs agreed that ADR communication can lead to anxiety and discontinuing treatment. Conclusion: The study indicates that, although orthopaedic physicians had positive attitudes towards providing ADR information to patients, improvement is needed in communicating NSAID risk information

Effect of market orientation, network capability and entrepreneurial orientation on international performance of small and medium enterprises (SMEs)

ABSTRACT: This study contributes to literature on the internationalization of SMEs by analysing the influence of International Market Orientation, Network Capability, and International Entrepreneurial Orientation on the International Performance of this kind of businesses. Particularly, both the direct effects of explanatory variables of international Performance and interdependence relations between them are analysed. Results obtained from a sample of 161 Mexican SMEs using SEM-PLS analysis show that the International Performance of this kind of businesses is favourably influenced by their Network Capability and International Entrepreneurial Orientation, but not by their International Market Orientation. Similarly, it is verified that interdependence relations exist among the explanatory variables of International Performance of SMEs, where positive impact of International Entrepreneurial Orientation is observed on Network Capability and the International Market Orientation of SMEs

cGMP-Dependent Protein Kinase I Is Crucial for Angiogenesis and Postnatal Vasculogenesis

Background Endothelium-derived nitric oxide plays an important role for the bone marrow microenvironment. Since several important effects of nitric oxide are mediated by cGMP-dependent pathways, we investigated the role of the cGMP downstream effector cGMP-dependent protein kinase I (cGKI) on postnatal neovascularization. Methodology/Principal Findings In a disc neovascularization model, cGKI -/- mice showed an impaired neovascularization as compared to their wild-type (WT) littermates. Infusion of WT, but not cGKI -/- bone marrow progenitors rescued the impaired ingrowth of new vessels in cGKI-deficient mice. Bone marrow progenitors from cGKI -/- mice showed reduced proliferation and survival rates. In addition, we used cGKI alpha leucine zipper mutant (LZM) mice as model for cGKI deficiency. LZM mice harbor a mutation in the cGKI alpha leucine zipper that prevents interaction with downstream signaling molecules. Consistently, LZM mice exhibited reduced numbers of vasculogenic progenitors and impaired neovascularization following hindlimb ischemia compared to WT mice. Conclusions/Significance Our findings demonstrate that the cGMP-cGKI pathway is critical for postnatal neovascularization and establish a new role for cGKI in vasculogenesis, which is mediated by bone marrow-derived progenitors

NOX2, p22phox and p47phox are targeted to the nuclear pore complex in ischemic cardiomyocytes colocalizing with local reactive oxygen species.

BACKGROUND: NADPH oxidases play an essential role in reactive oxygen species (ROS)-based signaling in the heart. Previously, we have demonstrated that (peri)nuclear expression of the catalytic NADPH oxidase subunit NOX2 in stressed cardiomyocytes, e.g. under ischemia or high concentrations of homocysteine, is an important step in the induction of apoptosis in these cells. Here this ischemia-induced nuclear targeting and activation of NOX2 was specified in cardiomyocytes. METHODS: The effect of ischemia, mimicked by metabolic inhibition, on nuclear localization of NOX2 and the NADPH oxidase subunits p22(phox) and p47(phox), was analyzed in rat neonatal cardiomyoblasts (H9c2 cells) using Western blot, immuno-electron microscopy and digital-imaging microscopy. RESULTS: NOX2 expression significantly increased in nuclear fractions of ischemic H9c2 cells. In addition, in these cells NOX2 was found to colocalize in the nuclear envelope with nuclear pore complexes, p22(phox), p47(phox) and nitrotyrosine residues, a marker for the generation of ROS. Inhibition of NADPH oxidase activity, with apocynin and DPI, significantly reduced (peri)nuclear expression of nitrotyrosine. CONCLUSION: We for the first time show that NOX2, p22(phox) and p47(phox) are targeted to and produce ROS at the nuclear pore complex in ischemic cardiomyocytes

Cilostazol Activates Function of Bone Marrow-Derived Endothelial Progenitor Cell for Re-endothelialization in a Carotid Balloon Injury Model

BACKGROUND: Cilostazol(CLZ) has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM)-derived endothelial progenitor cell (EPC) contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for endothelial regeneration, which is a key event for preventing atherosclerosis or restenosis after vascular intervention

Interpreting EEG alpha activity

Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes ‘alpha activity’ or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha “auto-rhythmicity” indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference