Can [125I]-Iodocyanopindolol Label β3-Adrenoceptors in Rat Urinary Bladder?

β3-Adrenoceptors have been demonstrated to mediate urinary bladder smooth muscle relaxation but proof of their expression at the protein level has been missing because of lack of suitable antibodies or radioligands. As among various available radioligands [125I]-iodocyanopindolol ([125I]-ICYP) exhibited the smallest problems in labeling cloned human β3-adrenoceptors in previous studies, we have explored its suitability to label β3-adrenoceptors in rat urinary bladder in saturation and competition radioligand binding experiments. Rat lung was used as an internal control and exhibited all characteristics expected from this tissue with regard to β1/β2-adrenoceptor labeling. Saturation and competition binding studies with [125I]-ICYP in rat bladder yielded saturable binding sites with an affinity compatible with β3-adrenoceptors. In competition experiments various agonists and antagonists largely exhibited a profile compatible with a population consisting largely of β3-adrenoceptors. However, the binding competition properties of ICI 118,551 and SR 59,230A were not easily explained by the idea of labeling a homogeneous β3-adrenoceptor population but interpretation of the data was limited by a high degree of non-specific binding in [125I]-ICYP concentrations required to label the receptors. We conclude that [125I]-ICYP can be used to label tissue β3-adrenoceptors but results obtained with this ligand have to be interpreted with caution

Measuring cortical connectivity in Alzheimer's disease as a brain neural network pathology: Toward clinical applications

Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer’s disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior–posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138–163

Sidekick compilation with xDSL

Traditionally, compiler researchers either conduct experiments within an existing production compiler or develop their own prototype compiler; both options come with trade-offs. On one hand, prototyping in a production compiler can be cumbersome, as they are often optimized for program compilation speed at the expense of software simplicity and development speed. On the other hand, the transition from a prototype compiler to production requires significant engineering work. To bridge this gap, we introduce the concept of sidekick compiler frameworks, an approach that uses multiple frameworks that interoperate with each other by leveraging textual interchange formats and declarative descriptions of abstractions. Each such compiler framework is specialized for specific use cases, such as performance or prototyping. Abstractions are by design shared across frameworks, simplifying the transition from prototyping to production. We demonstrate this idea with xDSL, a sidekick for MLIR focused on prototyping and teaching. xDSL interoperates with MLIR through a shared textual IR and the exchange of IRs through an IR Definition Language. The benefits of sidekick compiler frameworks are evaluated by showing on three use cases how xDSL impacts their development: teaching, DSL compilation, and rewrite system prototyping. We also investigate the trade-offs that xDSL offers, and demonstrate how we simplify the transition between frameworks using the IRDL dialect. With sidekick compilation, we envision a future in which engineers minimize the cost of development by choosing a framework built for their immediate needs, and later transitioning to production with minimal overhead

»If you look in there, there really is a vast desert …«

Fortund Weiterbildungen sind – nicht nur – für das schulische Personal notwendig, um den sich stetig wandelnden Anforderungen im Beruf gerecht zu werden. Im Kontext der Inklusion fühlen sich Kollegien allgemeiner Schulen nur unzureichend auf den Umgang mit einer heterogener werdenden Schülerschaft vorbereitet (Seitz und Haas 2015). Um inklusiven Unterricht zu realisieren, bedarf es demnach unbedingt der Teilnahme an Fortbildungen (Stellbrink 2012). Eine erste Herausforderung für die Lehrkräfte besteht darin, eigene Bedarfe zu erkennen und entsprechende Angebote zu finden. Im vorliegenden Beitrag wird der Frage nachgegangen, wie das bestehende Fortbildungsangebot beurteilt wird. Die Grundlage dafür bildet die inhaltsanalytische Auswertung von Interviewdaten aus Gesprächen mit schulischen und außerschulischen Expert*innen, die im Rahmen des vom BMBF-geförderten Projektes »StiEL – Schule tatsächlich inklusiv – Evidenzbasierte Weiterbildung für Lehrkräfte und weiteres pädagogisches Personal« im Land Brandenburg erhoben wurden. Im Ergebnis zeigt sich, dass die vorliegenden Strukturen auf der Angebotsseite bisweilen als wenig transparent bzw. konsistent beurteilt werden. Hier erscheint es u.a. sinnvoll, für die Realisierung einer fortlaufenden Lehrkräfteentwicklung zentrale(re) Strukturen zu etablieren, die ein umfassendes und unmittelbar zugängliches Angebot bereitstellen.Professional development is a prerequisite for school staff members to face the continuously changing requirements in education. In the context of inclusion most teachers do not feel adequately prepared in handling certain needs of a heterogenous student body (Seitz and Haas 2015). For implementing inclusive education in school there is an unavoidable need to get teachers into appropriate measures (Stellbrink 2012). For teachers, a first challenge is to get knowledge about their personal professional needs and further on to find respective in-service training programs. The following article asks for how schools organize the partici--shy--pation of their staff members in training activities. Based on qualitative content analysis of interview data it can be shown that the present training offers do not meet the needs that are asked for. We evaluated that the related structures are seen as fairly untransparent and inconsistent. So, with a focus on realizing a continuous in-service teacher program for inclusive education it might be helpful to implement structures that center resources and expertise to provide comprehensive and coherent teacher training programs

FTY720 treatment in the convalescence period improves functional recovery and reduces reactive astrogliosis in photothrombotic stroke

Background: The Sphingosine-1-phosphate (S1P) signaling pathway is known to influence pathophysiological processes within the brain and the synthetic S1P analog FTY720 has been shown to provide neuroprotection in experimental models of acute stroke. However, the effects of a manipulation of S1P signaling at later time points after experimental stroke have not yet been investigated. We examined whether a relatively late initiation of a FTY720 treatment has a positive effect on long-term neurological outcome with a focus on reactive astrogliosis, synapses and neurotrophic factors. Methods: We induced photothrombotic stroke (PT) in adult C57BL/6J mice and allowed them to recover for three days. Starting on post-stroke day 3, mice were treated with FTY720 (1 mg/kg b.i.d.) for 5 days. Behavioral outcome was observed until day 31 after photothrombosis and periinfarct cortical tissue was analyzed using tandem mass-spectrometry, TaqMan®analysis and immunofluorescence. Results: FTY720 treatment results in a significantly better functional outcome persisting up to day 31 after PT. This is accompanied by a significant decrease in reactive astrogliosis and larger post-synaptic densities as well as changes in the expression of vascular endothelial growth factor α (VEGF α). Within the periinfarct cortex, S1P is significantly increased compared to healthy brain tissue. Conclusion: Besides its known neuroprotective effects in the acute phase of experimental stroke, the initiation of FTY720 treatment in the convalescence period has a positive impact on long-term functional outcome, probably mediated through reduced astrogliosis, a modulation in synaptic morphology and an increased expression of neurotrophic factors

Competitive Edible Mushroom Production from Nonconventional Waste Biomass

Worldwide, there is an increase in acreage dedicated to the competitive production of fruits, vegetables, flowers, and palms crops as productive diversification for food, feed, fiber, and fuels. However, in developing countries, there is malnutrition by an inadequate diet caused by deficiency in quality or quantity of food. Therefore, options are needed for the production of foods, mainly of high protein content such as edible mushroom from by‐products. In Veracruz, Mexico, there is a large megadiversity of wastes derived from endemic plants, fruits, legumes, pods, leaves, straws, and flowers that are generated in a large amount and are disposed off through open‐field burning without a specific use. The objective was to evaluate the potential of 30 nonconventional by‐products and wastes for the production of low‐cost oyster mushrooms Pleurotus ostreatus. Biological efficiency (BE) varied from 17.65 to 180% and at least the 60% of the evaluated substrates (BE greater than 50%) are viable for the production of mushroom Pleurotus especially in view of its low contamination in trials and abundance and availability and diversity throughout the agricultural year as wastes. Besides, the spent substrates were converted into organic manure compost, vermicompost and bocashi to close the cycle for new food production

Invasive candidiasis: comparison of management choices by infectious disease and critical care specialists

Objective: To compare the management of invasive candidiasis between infectious disease and critical care specialists. Design and setting: Clinical case scenarios of invasive candidiasis were presented during interactive sessions at national specialty meetings. Participants responded to questions using an anonymous electronic voting system. Patients and participants: Sixty-five infectious disease and 51 critical care physicians in Switzerland. Results: Critical care specialists were more likely to ask advice from a colleague with expertise in the field of fungal infections to treat Candida glabrata (19.5% vs. 3.5%) and C. krusei (36.4% vs. 3.3%) candidemia. Most participants reported that they would change or remove a central venous catheter in the presence of candidemia, but 77.1% of critical care specialists would start concomitant antifungal treatment, compared to only 50% of infectious disease specialists. Similarly, more critical care specialists would start antifungal prophylaxis when Candida spp. are isolated from the peritonal fluid at time of surgery for peritonitis resulting from bowel perforation (22.2% vs. 7.2%). The two groups equally considered Candida spp. as pathogens in tertiary peritonitis, but critical care specialists would more frequently use amphotericin B than fluconazole, caspofungin, or voriconazole. In mechanically ventilated patients the isolation of 104 Candida spp. from a bronchoalveolar lavage was considered a colonizing organism by 94.9% of infectious disease, compared to 46.8% of critical care specialists, with a marked difference in the use of antifungal agents (5.1% vs. 51%). Conclusions: These data highlight differences between management approaches for candidiasis in two groups of specialists, particularly in the reported use of antifungal

Epidemiology of Candidemia in Swiss Tertiary Care Hospitals: Secular Trends, 1991-2000

Candida species are among the most common bloodstream pathogens in the United States, where the emergence of azole-resistant Candida glabrata and Candida krusei are major concerns. Recent comprehensive longitudinal data from Europe are lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17 university and university-affiliated hospitals representing 79% of all tertiary care hospital beds in Switzerland. The number of transplantations and bloodstream infections increased significantly (P < .001). A total of 1137 episodes of candidemia were observed: Candida species ranked seventh among etiologic agents (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a 10-year period. C. albicans remained the predominant Candida species recovered (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei remained rare (2%). Fluconazole consumption increased significantly (P < .001). Despite increasing high-risk activities, the incidence of candidemia remained unchanged, and no shift to resistant species occurre