The Pressor Response to Concurrent Stimulation of the Mesencephalic Locomotor Region and Peripheral Sensory Afferents Is Attenuated in Normotensive but Not Hypertensive Rats

Central command (CC) and the exercise pressor reflex (EPR) regulate blood pressure during exercise. We previously demonstrated that experimental stimulation of the CC and EPR pathways independently contribute to the exaggerated pressor response to exercise in hypertension. It is known that CC and EPR modify one another functionally. Whether their interactive relationship is altered in hypertension, contributing to the generation of this potentiated blood pressure response, remains unknown. To address this issue, the pressor response to activation of the CC pathway with and without concurrent stimulation of the EPR pathway, and vice versa, was examined in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. In decerebrated, paralyzed animals, activation of the CC pathway was evoked by electrical stimulation of the mesencephalic locomotor region (MLR; 20–50 μA in 10-μA steps). Electrical stimulation of the sciatic nerve (SN, 3, 5, and 10 × motor threshold; MT) was used to activate hindlimb afferents known to carry EPR sensory information. In both WKY and SHR, the algebraic sum of the pressor responses to individual stimulation of the MLR and SN were greater than when both inputs were stimulated simultaneously. Although the blood pressure response to a constant level of SN stimulation was not significantly affected by concurrent MLR stimulation at variable intensities, the pressor response to a constant level of MLR simulation was significantly attenuated by concurrent SN stimulation in WKY but not in SHR. These findings suggest the interactive relationship between CC and the EPR is inhibitory in nature in both WKY and SHR. However, the neural occlusion between these central and peripheral pressor mechanisms is attenuated in hypertension

Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations

Ischemic heart disease (IHD) is the leading cause of death worldwide. Novel cardioprotective strategies are therefore required to improve clinical outcomes in patients with IHD. Although a large number of novel cardioprotective strategies have been discovered in the research laboratory, their translation to the clinical setting has been largely disappointing. The reason for this failure can be attributed to a number of factors including the inadequacy of the animal ischemia–reperfusion injury models used in the preclinical cardioprotection studies and the inappropriate design and execution of the clinical cardioprotection studies. This important issue was the main topic of discussion of the UCL-Hatter Cardiovascular Institute 6th International Cardioprotection Workshop, the outcome of which has been published in this article as the “Hatter Workshop Recommendations”. These have been proposed to provide guidance on the design and execution of both preclinical and clinical cardioprotection studies in order to facilitate the translation of future novel cardioprotective strategies for patient benefit

Mastering the Hard Stuff: The History of College Concrete-Canoe Races and the Growth of Engineering Competition Culture

This article details the history of college engineering competitions, originating with student concrete-canoe racing in the 1970s, through today’s multi-million-dollar international multiplicity of challenges. Despite initial differences between engineering educators and industry supporters over the ultimate purpose of undergraduate competitions, these events thrived because they evolved to suit many needs of students, professors, schools, corporations, professional associations, and the engineering profession itself. The twenty-first-century proliferation of university-level competitions in turn encouraged a trickling-down of technical contests to elementary-age children and high schools, fostering the institutionalization of what might be called a competition culture in engineering

Introducing EDEN ISS - A European project on advancing plant cultivation technologies and operations

Plant cultivation in large-scale closed environments is challenging and several key technologies necessary for space-based plant production are not yet space-qualified or remain in early stages of development. The EDEN ISS project foresees development and demonstration of higher plant cultivation technologies, suitable for future deployment on the International Space Station and from a long-term perspective, within Moon and Mars habitats. The EDEN ISS consortium will design and test essential plant cultivation technologies using an International Standard Payload Rack form factor cultivation system for potential testing on-board the International Space Station. Furthermore, a Future Exploration Greenhouse will be designed with respect to future planetary bio-regenerative life support system deployments. The technologies will be tested in a laboratory environment as well as at the highly-isolated German Antarctic Neumayer Station III. A small and mobile container-sized test facility will be built in order to provide realistic mass flow relationships. In addition to technology development and validation, food safety and plant handling procedures will be developed. This paper describes the goals and objectives of EDEN ISS and the different project phases and milestones. Furthermore, the project consortium will be introduced and the role of each partner within the project is explained

Comparing comorbidity measures for predicting mortality and hospitalization in three population-based cohorts

<p>Abstract</p> <p>Background</p> <p>Multiple comorbidity measures have been developed for risk-adjustment in studies using administrative data, but it is unclear which measure is optimal for specific outcomes and if the measures are equally valid in different populations. This research examined the predictive performance of five comorbidity measures in three population-based cohorts.</p> <p>Methods</p> <p>Administrative data from the province of Saskatchewan, Canada, were used to create the cohorts. The general population cohort included all Saskatchewan residents 20+ years, the diabetes cohort included individuals 20+ years with a diabetes diagnosis in hospital and/or physician data, and the osteoporosis cohort included individuals 50+ years with diagnosed or treated osteoporosis. Five comorbidity measures based on health services utilization, number of different diagnoses, and prescription drugs over one year were defined. Predictive performance was assessed for death and hospitalization outcomes using measures of discrimination (<it>c</it>-statistic) and calibration (Brier score) for multiple logistic regression models.</p> <p>Results</p> <p>The comorbidity measures with optimal performance were the same in the general population (<it>n </it>= 662,423), diabetes (<it>n </it>= 41,925), and osteoporosis (<it>n </it>= 28,068) cohorts. For mortality, the Elixhauser index resulted in the highest <it>c</it>-statistic and lowest Brier score, followed by the Charlson index. For hospitalization, the number of diagnoses had the best predictive performance. Consistent results were obtained when we restricted attention to the population 65+ years in each cohort.</p> <p>Conclusions</p> <p>The optimal comorbidity measure depends on the health outcome and not on the disease characteristics of the study population.</p

A Screening Pipeline for Antiparasitic Agents Targeting Cryptosporidium Inosine Monophosphate Dehydrogenase

Persistent diarrhea is a leading cause of illness and death among impoverished children, and a growing share of this disease burden can be attributed to the parasite Cryptosporidium. There are no vaccines to prevent Cryptosporidium infection, and the treatment options are limited and unreliable. Critically, no effective treatment exists for children or adults suffering from AIDS. Cryptosporidium presents many technical obstacles for drug discovery; perhaps the most important roadblock is the difficulty of monitoring drug action. Here we have developed a set of methods to accelerate the drug discovery process for cryptosporidiosis. We exploit the opportunities for experimental manipulation in the related parasite Toxoplasma to genetically engineer a Cryptosporidium model. This new model parasite mirrors the metabolism of Cryptosporidium for a particularly promising drug target that supplies the building blocks for DNA and RNA. Drug effectiveness can be assayed through simple fluorescence measurements for many candidates. Using this assay as an initial filter, and adapting other assays to a high throughput format, we identify several novel chemical compounds that exhibit markedly improved anti-cryptosporidial activity and excellent selectivity