The Rostral Migratory Stream Plays a Key Role in Intranasal Delivery of Drugs into the CNS

Background: The blood brain barrier (BBB) is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS), but the relative contributions are debated. Methods and Findings: In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum. Conclusions: This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before w

Gene Ontology annotation quality analysis in model eukaryotes

Functional analysis using the Gene Ontology (GO) is crucial for array analysis, but it is often difficult for researchers to assess the amount and quality of GO annotations associated with different sets of gene products. In many cases the source of the GO annotations and the date the GO annotations were last updated is not apparent, further complicating a researchers’ ability to assess the quality of the GO data provided. Moreover, GO biocurators need to ensure that the GO quality is maintained and optimal for the functional processes that are most relevant for their research community. We report the GO Annotation Quality (GAQ) score, a quantitative measure of GO quality that includes breadth of GO annotation, the level of detail of annotation and the type of evidence used to make the annotation. As a case study, we apply the GAQ scoring method to a set of diverse eukaryotes and demonstrate how the GAQ score can be used to track changes in GO annotations over time and to assess the quality of GO annotations available for specific biological processes. The GAQ score also allows researchers to quantitatively assess the functional data available for their experimental systems (arrays or databases)

Combining quantitative and qualitative breast density measures to assess breast cancer risk

Abstract Background Accurately identifying women with dense breasts (Breast Imaging Reporting and Data System [BI-RADS] heterogeneously or extremely dense) who are at high breast cancer risk will facilitate discussions of supplemental imaging and primary prevention. We examined the independent contribution of dense breast volume and BI-RADS breast density to predict invasive breast cancer and whether dense breast volume combined with Breast Cancer Surveillance Consortium (BCSC) risk model factors (age, race/ethnicity, family history of breast cancer, history of breast biopsy, and BI-RADS breast density) improves identifying women with dense breasts at high breast cancer risk. Methods We conducted a case-control study of 1720 women with invasive cancer and 3686 control subjects. We calculated ORs and 95% CIs for the effect of BI-RADS breast density and Volpara™ automated dense breast volume on invasive cancer risk, adjusting for other BCSC risk model factors plus body mass index (BMI), and we compared C-statistics between models. We calculated BCSC 5-year breast cancer risk, incorporating the adjusted ORs associated with dense breast volume. Results Compared with women with BI-RADS scattered fibroglandular densities and second-quartile dense breast volume, women with BI-RADS extremely dense breasts and third- or fourth-quartile dense breast volume (75% of women with extremely dense breasts) had high breast cancer risk (OR 2.87, 95% CI 1.84–4.47, and OR 2.56, 95% CI 1.87–3.52, respectively), whereas women with extremely dense breasts and first- or second-quartile dense breast volume were not at significantly increased breast cancer risk (OR 1.53, 95% CI 0.75–3.09, and OR 1.50, 95% CI 0.82–2.73, respectively). Adding continuous dense breast volume to a model with BCSC risk model factors and BMI increased discriminatory accuracy compared with a model with only BCSC risk model factors (C-statistic 0.639, 95% CI 0.623–0.654, vs. C-statistic 0.614, 95% CI 0.598–0.630, respectively; P < 0.001). Women with dense breasts and fourth-quartile dense breast volume had a BCSC 5-year risk of 2.5%, whereas women with dense breasts and first-quartile dense breast volume had a 5-year risk ≤ 1.8%. Conclusions Risk models with automated dense breast volume combined with BI-RADS breast density may better identify women with dense breasts at high breast cancer risk than risk models with either measure alone

Crop Updates 2010 - Farming Systems

This session covers twenty papers from different authors: Pests and Disease 1. Preserving phosphine for use in Grain Storage Industry, Christopher R Newman, Department of Agriculture and Food Farming Systems Research 2. Demonstrating the benefits of grazing canola in Western Australia, Jonathan England, Stephen Gherardi and Mohammad Amjad, Department of Agriculture and Food 3. Buloke barley yield when pasture-cropped across subtropical perennial pastures, David Ferris, Department of Agriculture and Food, Phil Ward and Roger Lawes, CSIRO 4. Is pasture cropping viable in WA? Grower perceptions and EverCrop initiatives to evaluate, David Ferris, Tim Wiley, Perry Dolling, Department of Agriculture and Food, Philip Barrett-Lennard, Evergreen farming 5. Best-bet management for dual-purpose canola, John Kirkegaard, Susan Sprague, Hugh Dove and Walter Kelman, CSIRO, Canberra, Peter Hamblin, Agritech Research, Young, NSW 6. Pasture in cropping systems – with and without sheep, Brad Nutt and Angelo Loi, Department of Agriculture and Food 7. Can technology substitute for a lupin break? Wayne Parker, Department of Agriculture and Food 8. Canola row spacing with and without long term stubble retention on a sandy clay loam at Merredin, Glen Riethmuller, Department of Agriculture and Food 9. Impact of stubble retention on water balance and crop yield, Phil Ward1, Ken Flower2,3, Neil Cordingley2 and Shayne Micin1, 1CSIRO, Wembley, Western Australia, 2Western Australian No-Till Farmers Association, 3University of Western Australia Analysis and Modelling 10. Using POAMA rainfall forecasts for crop management in South-West WA, Senthold Asseng1, Peter McIntosh2,3, Mike Pook2,3, James Risbey2,3, Guomin Wang3, Oscar Alves3, Ian Foster4, Imma Farre4 and Nirav Khimashia1, 1CSIRO Plant Industry, Perth, 2CSIRO Marine and Atmospheric Research, Hobart, 3Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne, 4Department of Agriculture and Food 11. Adaption to changing climates and variability – results of the Agribusiness Changing Climates regional workshop, Anderson W3, Beard D3, Blake J3, Grieve R1, Lang M3, Lemon J3, McTaggart R3, Gray D3, Price M2 and Stephens D3, 1Roderick Grieve Farm Management Consultants, 2Coffey International P/L, 3Department of Agriculture and Food 12. Farmers’ management of seasonal variability and climate change in WA, DA Beard, DM Gray, P Carmody, Department of Agriculture and Food 13. Is there a value in having a frost forecast for wheat in South-West WA? Imma Farre1, Senthold Asseng2, Ian Foster1 and Doug Abrecht3, 1Department of Agriculture and Food, CSIRO, Floreat, 2CSIRO Plant Industry, Perth 3Department of Agriculture and Food, Centre for Cropping Systems 14. Does buying rainfall pay? Greg Kirk, Planfarm Agricultural Consultants 15. Which region in the WA wheatbelt makes best use of rainfall? Peter Rowe, Bankwest Agribusiness 16. POAMA – the Predictive Ocean-Atmosphere Model for Australia, Guomin Wang and Oscar Alves, Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne 17. Exploring the link between water use efficiency and farm profitability, Cameron Weeks, Planfarm and Peter Tozer, PRT Consulting Precision Agriculture 18. A plethora of paddock information is available – how does it stack up? Derk Bakker, Department of Agriculture and Food 18. Variable rate prescription mapping for lime inputs based on electromagnetic surveying and deep soil testing, Frank D’Emden, Quenten Knight and Luke Marquis, Precision Agronomics, Australia 19. Trial design and analysis using precision agriculture and farmer’s equipment, Roger Lawes, CSIRO Sustainable Ecosystems, Centre for Environment and Life Sciences, Floreat 20. Farmer perspectives of precision agriculture in Western Australia: Issues and the way forward, Dr Roger Mandel, Curtin Universit

Forced, not voluntary, exercise effectively induces neuroprotection in stroke

Previous treadmill exercise studies showing neuroprotective effects have raised questions as to whether exercise or the stress related to it may be key etiologic factors. In this study, we examined different exercise regimens (forced and voluntary exercise) and compared them with the effect of stress-only on stroke protection. Adult male Sprague-Dawley rats (n = 65) were randomly assigned to treatment groups for 3 weeks. These groups included control, treadmill exercise, voluntary running wheel exercise, restraint, and electric shock. Levels of the stress hormone, corticosterone, were measured in the different groups using ELISA. Animals from each group were then subjected to stroke induced by a 2-h middle cerebral artery (MCA) occlusion followed by 48-h reperfusion. Infarct volume was determined in each group, while changes in gene expression of stress-induced heat shock proteins (Hsp) 27 and 70 were compared using real-time PCR between voluntary and treadmill exercise groups. The level of corticosterone was significantly higher in both stress (P < 0.05) and treadmill exercise (P < 0.05) groups, but not in the voluntary exercise group. Infarct volume was significantly reduced (P < 0.01) following stroke in rats exercised on a treadmill. However, the amelioration of damage was not duplicated in voluntary exercise, even though running distance in the voluntary exercise group was significantly (P < 0.01) longer than that of the forced exercise group (4,828 vs. 900 m). Furthermore, rats in the electric shock group displayed a significantly increased (P < 0.01) infarct volume. Expression of both Hsp 27 and Hsp 70 mRNA was significantly increased (P < 0.01) in the treadmill exercise group as compared with that in the voluntary exercise group. These results suggest that exercise with a stressful component, rather than either voluntary exercise or stress alone, is better able to reduce infarct volume. This exercise-induced neuroprotection may be attributable to up-regulation of stress-induced heat shock proteins 27 and 70

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Intranasal uptake of CTG into the hippocampus and cerebellum.

<p>Anesthetized mice received intranasal administration of CTG (6 µl) or vehicle (PBS) into both nares slowly over a period of ten minutes. Mice remained anesthetized for an additional 20 minutes in a supine position to allow absorption of the tracer through the olfactory epithelium and into the olfactory blub. Five hours later, mice were euthanized and perfused with 4% PFA, and the brains sectioned into 12 µm slices. CTG positive cells are labeled green. Vehicle treated mice did not produce any signal (data not shown).</p

Intranasal uptake of CTG into the olfactory bulb, choroid plexus, and cortex.

<p>Anesthetized mice received intranasal administration of CTG (6 µl) or vehicle (PBS). Mice remained anesthetized for an additional 20 minutes in a supine position. Five hours later, mice were euthanized and perfused with 4% PFA, and the brains sectioned into 12 µm slices. Nuclei were counterstained with DAPI (Blue). CTG cells are labeled green. No signal was detected in the vehicle treated mice (data not shown).</p

Disruption of the RMS prevents intranasal delivery of peptides.

<p>Mice were anesthetized and the RMS dissected through a small burr-hole over the olfactory bulb. ¹²⁵I-EPO or ¹²⁵I-Calcitonin was administered intranasally 20 minutes later. The mice were then euthanized after 20, 60, or 120 minutes, and radioactivity was measured in brain tissue, lung tissue, blood and nasal swabs using a scintillation counter (Perkin Elmer). Data is expressed as a percentage of the total amount of the applied radioligand (mean ± SD, n = 3). *p<0.01, percent of radioligand in the brain compared to lung, blood and nasal swabs at each time point. ^#p<0.01, percent of radioligand in the brain compared to lung and blood only, ^‡p<0.01, percent of radioligand in the brain at 60 or 120 minutes versus in the brain at 20 minutes.</p