Hospitals as innovators in the health-care system: a literature review and research agenda

This paper aims to improve understanding of the role of hospitals in the generation of innovations. It presents a systematic and critical review of the interdisciplinary literature that addresses the links between the activities of hospitals and medical innovation. It identifies three major research streams: studies of the contribution of medical research and clinical staff to innovation, analyses of novel practices developed and diffused in hospitals, and evolutionary studies of technical change in the context of human health care. This is a highly heterogeneous body of literature, in which comprehensive theoretical frameworks are rare, and empirical studies have tended to focus on a narrow range of hospitals' innovation activities. The paper introduces and discusses a framework integrating different perspectives that can be used to analyze the functions performed by hospitals at the intersection with different partners in the health innovation system and at different stages of innovation trajectories. On the basis of current gaps in the literature, a research agenda is discussed for a relational and co-evolutionary approach to the study of hospitals as innovators.Research for this article was funded by the Research Council of Norway under the project “Synergies and tensions in innovation in the life sciences,” as well as by the South-Eastern Norway Regional Health Authority and the University of Oslo

Drug Induced Cardiotoxicity: Mechanism, Prevention and Management

Drug-induced cardiotoxicity is a major adverse effect that has been encountered for some clinically important drugs especially antineoplastic agents. This toxicity has previously led to the post-marketing withdrawal of numerous pharmacologically active drugs and limits the efficacy of other clinically useful ones. Currently, assessing the cardiotoxicity potential is a crucial parameter in drug development, and many models have been established to facilitate its prediction to avoid such toxicity. In this chapter, we will briefly discuss the mechanism of drug-induced cardiotoxicity, risk factors, how to prevent, early detection and/or management from a pharmacological and toxicological point of view

Finite Element Modeling of Binary Acoustic Fresnel Lenses

Binary acoustic Fresnel lenses (BAFLs) have recently emerged as possible replacements for spherical lenses for applications in acoustic microscopy. BAFLs are surface relief structures that are relatively easy to manufacture compared to conventional spherical lenses. While the latter requires careful grinding and polishing, the former can be easily fabricated to sub-micron dimension accuracy using existing VLSI etching technology. The term binary arises from the fact that each masking step during the lens production creates two phase levels. Therefore, a total of 2 n phase levels are created in n masking etching steps. A special case is when n = 1 (2 phase levels), which corresponds to the conventional Fresnel lens (zone plate)

Endófitos fúngicos relacionados con la maduración natural y compuestos aromáticos en frutos de especies de la orquídea del género Vanilla

The biotic interaction between plants and endophytic fungi strengthens the adaptive capacity of the hosts against environmental disturbances, and confers nutrition and protection benefits to the associated microorganisms. Studies associated with endophytic fungi report their presence in the greatest diversity of existing plants. In hosts such as Cannabis, the interaction with endophytic fungi favors the production of secondary metabolites and phytohormones that participate in obtaining organoleptic properties such as flavors and aromas. However, the research carried out in the Vanilla genus is scarce, making it difficult to understand the functions that these microorganisms can perform for the benefit of the host. In relation to Vanilla, the fruits of species within the aromatic clade are distinguished by the presence of aromatic compounds, which increase their content during ripening. Some studies have shown that in the fruits of this orchid there are endophytic fungi possibly associated with the ripening process that is accelerated by curing, but few of these studies have evaluated the activity of these fungi related to the natural ripening of the fruit. In this review, scientific literature related to the knowledge of fungal endophyte communities and their possible contribution to the ripening and production of aromatic compounds in vanilla fruits is compiled. Research opportunities are identified to develop future studies on the role of fungal microorganisms in obtaining metabolites and aromatic precursors from the fruits of Vanilla species, both in wild conditions and in commercial crops.La interacción biótica entre plantas y hongos endófitos fortalece la capacidad adaptativa de los hospederos frente a perturbaciones del ambiente, y confiere a los microorganismos asociados beneficios de nutrición y protección. Estudios asociados a hongos endófitos reportan su presencia en la mayor diversidad de plantas existentes. En diferentes plantas hospederas,  la interacción con hongos endófitos favorece la producción de metabolitos secundarios y fitohormonas que participan en la obtención de propiedades organolépticas como los sabores y los aromas. Sin embargo, las investigaciones desarrolladas en el género Vanilla son escasas, dificultando el entendimiento de las funciones que pueden desempeñar estos microorganismos en beneficio del hospedero. Con relación a Vanilla, los frutos de especies dentro del clado aromático se distinguen por la presencia de compuestos aromáticos, que aumentan su contenido durante la maduración. Algunos estudios, han demostrado que en los frutos de esta orquídea existen hongos endófitos posiblemente asociados al proceso de maduración que se acelera mediante el curado, pero pocos de estos estudios, han evaluado la actividad de dichos hongos relacionados con la maduración del fruto de forma natural. En esta revisión se recopila literatura científica relacionada con el conocimiento de las comunidades de endófitos fúngicos y su posible aporte en la maduración y producción de compuestos aromáticos en los frutos de vainilla. Se identifican oportunidades de investigación para desarrollar futuros estudios sobre el papel de los microorganismos fungosos para la obtención de metabolitos y precursores aromáticos de los frutos en especies de Vanilla, tanto en condiciones silvestres como en cultivos comerciales

ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells

ATP is well known for its role as an intracellular energy source. However, there is increasing awareness of its role as an extracellular messenger molecule (Burnstock, 1997). Although evidence for the presence of receptors for extracellular ATP on skeletal myoblasts was first published in 1983 (Kolb and Wakelam), their physiological function has remained unclear. In this paper we used primary cultures of rat skeletal muscle satellite cells to investigate the role of purinergic signaling in muscle formation. Using immunocytochemistry, RT-PCR, and electrophysiology, we demonstrate that the ionotropic P2X5 receptor is present on satellite cells and that activation of a P2X receptor inhibits proliferation, stimulates expression of markers of muscle cell differentiation, including myogenin, p21, and myosin heavy chain, and increases the rate of myotube formation. Furthermore, we demonstrate that ATP application results in a significant and rapid increase in the phosphorylation of MAPKs, particularly p38, and that inhibition of p38 activity can prevent the effect of ATP on cell number. These results not only demonstrate the existence of a novel regulator of skeletal muscle differentiation, namely ATP, but also a new role for ionotropic P2X receptors in the control of cell fate

Impact of plant genotype and plant habitat in shaping bacterial pathobiome: a comparative study in olive tree

Plant-inhabiting microorganisms interact directly with each other affecting disease progression. However, the role of host plant and plant habitat in shaping pathobiome composition and their implication for host susceptibility/resistance to a particular disease are currently unknown. For the elucidation of these questions, both epiphytic and endophytic bacterial communities, present in asymptomatic and symptomatic twigs from olive cultivars displaying different susceptibilities to olive knot (OK) disease, were investigated using culturing methods. OK disease was the main driver of the bacterial community, causing changes on their diversity, abundance and composition. OK disease effect was most notorious on OK-susceptible cultivar and when considering the endophytic communities. Plant habitat (epiphytes vs. endophytes) also contributed to the bacterial community assembling, in particular on symptomatic twigs (knots) of OK-susceptible cultivar. In contrast, host cultivar had little effect on the bacterial community composition, but OK-symptomatic twigs (knots) revealed to be more affected by this driver. Overall, the pathobiome seems to result from an intricate interaction between the pathogen, the resident bacteria, and the plant host. Specific bacterial genera were associated to the presence or absence of OK disease in each cultivar. Their ability to trigger and/or suppress disease should be studied in the future.The authors are grateful to the FEDER and Foundation for Science and Technology (FCT, Portugal) under Programme PT2020 for financial support to CIMO (UIDB/00690/2020) and BioISI (UID/MULTI/04046/2013), as well as the Horizon 2020, the European Union's Framework Programme for Research and Innovation, for financial support the project PRIMA/0002/2018 INTOMED -Innovative tools to combat crop pests in the Mediterranean. D. Mina thanks FCT, POPH-QREN and FSE for SFRH-BD-105341/2014 grant

Epiphytic and endophytic bacteria on olive tree phyllosphere: Exploring tissue and cultivar effect

Variation on bacterial communities living in the phyllosphere as epiphytes and endophytes has been attributed to plant host effects. However, there is contradictory or inconclusive evidence regarding the effect of plant genetics (below the species' level) and of plant tissue type on phyllosphere bacterial community assembly, in particular when epiphytes and endophytes are considered simultaneously. Here, both surface and internal bacterial communities of two olive (Olea europaea) cultivars were evaluated in twigs and leaves by molecular identification of cultivable isolates, with an attempt to answer these questions. Overall,Proteobacteria,ActinobacteriaandFirmicuteswere the dominant phyla, being epiphytes more diverse and abundant than endophytes. Host genotype (at cultivar level) had a structuring effect on the composition of bacterial communities and, in a similar way, for both epiphytes and endophytes. Plant organ (leaf vs. twig) control of the bacterial communities was less evident when compared with plant genotype and with a greater influence on epiphytic than on endophytic community structure. Each olive genotype/plant organ was apparently selective towards specific bacterial operational taxonomic units (OTUs), which may lead to specific feedbacks on fitness of plant genotypes. Bacterial recruitment was observed to happen mainly within epiphytes than in endophytes and in leaves as compared with twigs. Such host specificity suggested that the benefits derived from the plant-bacteria interaction should be considered at genetic levels below the species.The authors are grateful to the FEDER and Foundation for Science and Technology (FCT, Portugal) under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2019) and BioISI (UID/MULTI/04046/2013), as well as the Horizon 2020, the European Union’s Framework Programme for Research and Innovation, for financial support the project PRIMA/0002/2018 INTOMED—Innovative tools to combat crop pests in the Mediterranean. D. Mina thanks FCT, POPH-QREN and FSE for SFRH-BD-105341/2014 grant

Biological control of Pseudomonas savastanoi pv. savastanoi by two bacterial isolated from olive tree phyllosphere

Olive knot disease, caused by the bacterium Pseudomonas savastanoi pv. savastanoi (Psv), has been responsible for high economical crop losses in olive orchards, especially in Mediterranean countries. Olive knot cannot be eradicated once it is established in an orchard, and therefore its control is based on preventive measures. Laboratory experiments previously performed by us have showed the capacity of some bacterial species, isolated from olive tree phyllosphere, to inhibited Psv growth. In the present work, the two most promising bacterial isolates (i.e. Frondihabitans sp. and Paenibacillus sp.) were evaluated for the control of Psv in olive plantlets (Olea europaea L.) under greenhouse conditions, to predict their effect in a more natural condition. In pot experiments, two-year-old olive plants cv. Cobrançosa were inoculated with the antagonistic bacteria and Psv individually or in combination. Inoculations were performed in wounds previously made in three different sites of the main stem. Thirty replicate plants were used per strain. The plants were observed for symptom development and the number of bacteria on the inoculation sites was periodically evaluated, for up to 120 days after inoculation. To quantify the reduction of symptom expression, knots were excised from stems and their weights were compared between treatments. Inoculation with Psv resulted in the formation of knots with significantly higher weight values compared to plants inoculated simultaneously with Psv and antagonistic bacteria. Both tested bacterial also showed the capacity to reduce the amount of Psv in the inoculation sites, suggesting their effectiveness in controlling the multiplication of the pathogen. Data presented here demonstrate for the first time the potential of these bacteria for suppression of olive knot, and these two species should be considered in the future as potential biocontrol agents against Psv.info:eu-repo/semantics/publishedVersio