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Binocular Vision: Joining Up the Eyes. - Current biology : CB
To provide a unitary view of the external world, signals from the two eyes must be combined: a new study pinpoints the location in the human brain where the requisite combination occurs.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
Tissue plasminogen activator treatment of bilateral pulmonary emboli in a pediatric patient supported with a ventricular assist device. - Pediatric transplantation
Bleeding and thrombosis are well-known potential complications of VAD support. We present a pediatric patient who developed massive bilateral pulmonary emboli while on BiVAD support that was successfully treated with intravenous tPA and bridged to heart transplant.Â© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
r-bPiDI, an Î±6Î²2* Nicotinic Receptor Antagonist, Decreases Nicotine-Evoked Dopamine Release and Nicotine Reinforcement. - Neurochemical research
Î±6Î²2* nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic neurons mediate nicotine-evoked dopamine (DA) release and nicotine reinforcement. Î±6Î²2* antagonists inhibit these effects of nicotine, such that Î±6Î²2* receptors serve as therapeutic targets for nicotine addiction. The present research assessed the neuropharmacology of 1,10-bis(3-methyl-5,6-dihydropyridin-1(2H)-yl)decane (r-bPiDI), a novel small-molecule, tertiary amino analog of its parent compound, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI). bPiDI was previously shown to inhibit both nicotine-evoked DA release and the reinforcing effects of nicotine. In the current study, r-bPiDI inhibition of [(3)H]nicotine and [(3)H]methyllycaconitine binding sites was evaluated to assess interaction with the recognition binding sites on Î±4Î²2* and Î±7* nAChRs, respectively. Further, r-bPiDI inhibition of nicotine-evoked DA release in vitro in the absence and presence of Î±-conotoxin MII and following chronic in vivo nicotine administration were determined. The ability of r-bPiDI to decrease nicotine self-administration and food-maintained responding was also assessed. Results show that r-bPiDI did not inhibit [(3)H]nicotine or [(3)H]methyllycaconitine binding, but potently (IC50Â =Â 37.5Â nM) inhibited nicotine-evoked DA release from superfused striatal slices obtained from either drug naÃ¯ve rats or from those repeatedly treated with nicotine. r-bPiDI inhibition of nicotine-evoked DA release was not different in the absence or presence of Î±-conotoxin MII, indicating that r-bPiDI acts as a potent, selective Î±6Î²2* nAChR antagonist. Acute systemic administration of r-bPiDI specifically decreased nicotine self-administration by 75Â %, and did not alter food-maintained responding, demonstrating greater specificity relative to bPiDI and bPiDDB, as well as the tertiary amino analog r-bPiDDB. The current work describes the discovery of r-bPiDI, a tertiary amino, Î±-conotoxin MII-like small molecule that acts as a potent and selective antagonist at Î±6Î²2* nAChRs to specifically decrease nicotine self-administration in rats, thus, establishing r-bPiDI as a lead compound for development as a treatment for nicotine addiction.
Predicting and managing heat dissipation from a neural probe. - Biomedical microdevices
Light stimulating neural probes are rapidly increasing our understanding of neural pathways. Relocating the externally coupled light source to the probe tip has the potential to dramatically improve the flexibility of the technique. However, this approach would generate heat within the embedded probe where even minor temperature excursions could easily damage tissues under study. A COMSOL model was used to study the thermal effects of these heated probes in the brain including blood perfusion and metabolic heating, and to investigate the effect of passive methods for improving heat dissipation. The probe temperature initially decreases with insertion depth, and then becomes steady. Extending the probe beyond the heated region has a similar effect, while increasing the size of the heated region steadily decreases the probe temperature. Increasing the thermal conductivity of the probe promotes spreading, decreasing the probe temperature. The effects of insertion depth and probe power dissipation were experimentally tested with a microfabricated, heated mock neural probe. The heated probe was tested in 0.65 % agarose gel at room temperature and in ex vivo cow brain at body temperature. The thermal resistance between the probe and the neural tissue or agarose gel was determined at a range of insertion depths and compared to the COMSOL model.
Significant predictors of poor quality of life in older asthmatics. - Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
Morbidity and mortality from asthma are high in older adults and quality of life (QOL) might be lower, although standardized measurements of QOL have not been validated in this population.To determine predictors of asthma-related QOL in older adults.Allergy and pulmonary outpatients (nÂ = 164) at least 65 years old with an objective diagnosis of asthma completed the Mini-Asthma Quality of Life Questionnaire (mAQLQ). Demographics, medical history, and mean value for daily elemental carbon attributable to traffic, a surrogate for diesel exposure, were obtained. Regression analysis was used to determine predictors of mAQLQ scores.Total mAQLQ (mean Â± SD 5.4 Â± 1.1) and symptom, emotional, and activity domain scores were similar to those of younger populations, whereas environmental domain scores (4.4 Â± 1.7) appeared lower. Poorer mAQLQ scores were significantly associated with emergency department visits (adjusted Î² [aÎ²]Â =Â -1.3, where Î²Â values indicate the strength and direction of association, P < .0001) and with poorer scores on the Asthma Control Questionnaire (aÎ²Â =Â -0.7, P < .0001). Greater ECAT exposure (aÎ²Â =Â -1.6, P < .02), female sex (aÎ²Â =Â -0.4, P < .006), body mass index of at least 30 kg/m(2) (aÎ²Â =Â -0.4, P < .01), gastroesophageal reflux (aÎ²Â =Â -0.4, P < .01), nonatopic status (aÎ²Â =Â -0.5, P < .002), and asthma onset before 40 years of age (aÎ²Â =Â -0.5, P < .004) were significantly associated with poorer mAQLQ scores.The mAQLQ scores in older adults with stable asthma were similar to those in younger populations and were predictive of other measurements of asthma control, verifying that the mAQLQ is an appropriate tool in older adults with asthma. Traffic pollution exposure was the strongest predictor of poorer asthma-related QOL in older adults with asthma.Copyright Â© 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Herbivory and Competition of Tibetan Steppe Vegetation in Winter Pasture: Effects of Livestock Exclosure and Plateau Pika Reduction. - PloS one
Rangeland degradation has been identified as a serious concern in alpine regions of western China on the Qinghai-Tibetan plateau (QTP). Numerous government-sponsored programs have been initiated, including many that feature long-term grazing prohibitions and some that call for eliminating pastoralism altogether. As well, government programs have long favored eliminating plateau pikas (Ochotona curzoniae), assumed to contribute to degraded conditions. However, vegetation on the QTP evolved in the presence of herbivory, suggesting that deleterious effects from grazing are, to some extent, compensated for by reduced plant-plant competition. We examined the dynamics of common steppe ecosystem species as well as physical indicators of rangeland stress by excluding livestock and reducing pika abundance on experimental plots, and following responses for 4 years. We established 12 fenced livestock exclosures within pastures grazed during winter by local pastoralists, and removed pikas on half of these. We established paired, permanent vegetation plots within and outside exclosures and measured indices of erosion and biomass of common plant species. We observed modest restoration of physical site conditions (reduced bare soil, erosion, greater vegetation cover) with both livestock exclusion and pika reduction. As expected in areas protected from grazing, we observed a reduction in annual productivity of plant species avoided by livestock and assumed to compete poorly when protected from grazing. Contrary to expectation, we observed similar reductions in annual productivity among palatable, perennial graminoids under livestock exclusion. The dominant grass, Stipa purpurea, displayed evidence of density-dependent growth, suggesting that intra-specific competition exerted a regulatory effect on annual production in the absence of grazing. Complete grazing bans on winter pastures in steppe habitats on the QTP may assist in the recovery of highly eroded pastures, but may not increase annual vegetative production.
Activatable and Cell-Penetrable Multiplex FRET Nanosensor for Profiling MT1-MMP Activity in Single Cancer Cells. - Nano letters
We developed a quantum-dot-based fluorescence resonance energy transfer (QD-FRET) nanosensor to visualize the activity of matrix metalloproteinase (MT1-MMP) at cell membrane. A bended peptide with multiple motifs was engineered to position the FRET pair at a close proximity to allow energy transfer, which can be cleaved by active MT1-MMP to result in FRET changes and the exposure of cell penetrating sequence. Via FRET and penetrated QD signals, the nanosensor can profile cancer cells.
A macro-ecological perspective on crassulacean acid metabolism (CAM) photosynthesis evolution in Afro-Madagascan drylands: Eulophiinae orchids as a case study. - The New phytologist
Crassulacean acid metabolism (CAM) photosynthesis is an adaptation to water and atmospheric CO2 deficits that has been linked to diversification in dry-adapted plants. We investigated whether CAM evolution can be associated with the availability of new or alternative niches, using Eulophiinae orchids as a case study. Carbon isotope ratios, geographical and climate data, fossil records and DNA sequences were used to: assess the prevalence of CAM in Eulophiinae orchids; characterize the ecological niche of extant taxa; infer divergence times; and estimate whether CAM is associated with niche shifts. CAM evolved in four terrestrial lineages during the late Miocene/Pliocene, which have uneven diversification patterns. These lineages originated in humid habitats and colonized dry/seasonally dry environments in Africa and Madagascar. Additional key features (variegation, heterophylly) evolved in the most species-rich CAM lineages. Dry habitats were also colonized by a lineage that includes putative mycoheterotrophic taxa. These findings indicate that the switch to CAM is associated with environmental change. With its suite of adaptive traits, this group of orchids represents a unique opportunity to study the adaptations to dry environments, especially in the face of projected global aridification.Â© 2015 The Authors. New Phytologist Â© 2015 New Phytologist Trust.
Predictors of new graduate nurses' satisfaction with their transitional support programme. - Journal of nursing management
To examine the influence of new graduate nurses' (NGNs) personal and situational factors on their satisfaction with the practice environment.Transitional support programmes are widely used to provide professional support for NGNs' transitioning-to-practice. However, little is known about whether personal characteristics and situational factors influence NGNs' satisfaction with the practice environment.This was a cross-sectional survey. NGNs were surveyed approximately 8Â weeks after commencement of the support programme. In addition to socio-demographic and situational data, two validated, standardised instruments were administered: the Manchester Clinical Supervision Scale (MCSS-26) and the Practice Environment Scale Australia (PES-AUS).A total of 109 NGNs completed the survey. Three independent and significant predictors of NGNs' satisfaction were: (1) unit satisfaction (standardised beta, Î²Â =Â 0.41); (2) satisfaction with the clinical supervision (Î²Â =Â 0.31); and (3) assigned unit: critical-care areas (Î²Â =Â -0.17), explaining 32.5% of the variance. Conclusion This study demonstrates the importance of clinical supervision and unit level support on satisfaction, and the need for additional support for NGNs assigned to critical-care areas.The findings of this study suggest there are modifiable situational factors that influence NGNs' satisfaction with the practice environment, and allocating NGNs to critical-care areas on their first rotation should be avoided.Â© 2015 John Wiley & Sons Ltd.
Model Selection of the Effect of Binary Exposures over the Life Course. - Epidemiology (Cambridge, Mass.)
Epidemiologists are often interested in examining the effect on a later-life outcome of an exposure measured repeatedly over the life course. When different hypotheses for this effect are proposed by competing theories, it is important to identify those most supported by observed data as a first step toward estimating causal associations. One method is to compare goodness-of-fit of hypothesized models with a saturated model, but it is unclear how to judge the "best" out of two hypothesized models that both pass criteria for a good fit. We developed a new method using the least absolute shrinkage and selection operator to identify which of a small set of hypothesized models explains most of the observed outcome variation. We analyzed a cohort study with repeated measures of socioeconomic position (exposure) through childhood, early- and mid-adulthood, and body mass index (outcome) measured in mid-adulthood. We confirmed previous findings regarding support or lack of support for the following hypotheses: accumulation (number of times exposed), three critical periods (only exposure in childhood, early- or mid-adulthood), and social mobility (transition from low to high socioeconomic position). Simulations showed that our least absolute shrinkage and selection operator approach identified the most suitable hypothesized model with high probability in moderately sized samples, but with lower probability for hypotheses involving change in exposure or highly correlated exposures. Identifying a single, simple hypothesis that represents the specified knowledge of the life course association allows more precise definition of the causal effect of interest.
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