Anti-platelet drugs and their necessary interaction with endothelial mediators and platelet cyclic nucleotides for therapeutic efficacy

This work was supported by the British Heart Foundation [FS/12/53/29643] to RBK

Drug Delivery Strategies for Platinum Based Chemotherapy

Few chemotherapeutics have had such an impact on cancer management as cis-diamminedichloridoplatinum(II) (CDDP), also known as cisplatin. The first member of the platinum based drug family, CDDP's potent toxicity in disrupting DNA replication has led to its widespread use in multi-drug therapies, with particular benefit in patients with testicular cancers. However, CDDP also produces significant side effects that limit the maximum systemic dose. Various strategies have been developed to address this challenge including encapsulation within micro- or nanocarriers and the use of external stimuli such as ultrasound to promote uptake and release. The aim of this article is to look at these strategies and recent scientific and clinical developments

Approximating Mexican highways with slime mould

Plasmodium of Physarum polycephalum is a single cell visible by unaided eye. During its foraging behavior the cell spans spatially distributed sources of nutrients with a protoplasmic network. Geometrical structure of the protoplasmic networks allows the plasmodium to optimize transport of nutrients between remote parts of its body. Assuming major Mexican cities are sources of nutrients how much structure of Physarum protoplasmic network correspond to structure of Mexican Federal highway network? To find an answer undertook a series of laboratory experiments with living Physarum polycephalum. We represent geographical locations of major cities by oat flakes, place a piece of plasmodium in Mexico city area, record the plasmodium's foraging behavior and extract topology of nutrient transport networks. Results of our experiments show that the protoplasmic network formed by Physarum is isomorphic, subject to limitations imposed, to a network of principle highways. Ideas and results of the paper may contribute towards future developments in bio-inspired road planning

An international prospective cohort study of mobile phone users and health (COSMOS): Factors affecting validity of self-reported mobile phone use.

This study investigates validity of self-reported mobile phone use in a subset of 75 993 adults from the COSMOS cohort study. Agreement between self-reported and operator-derived mobile call frequency and duration for a 3-month period was assessed using Cohen's weighted Kappa (κ). Sensitivity and specificity of both self-reported high (≥10 calls/day or ≥4h/week) and low (≤6 calls/week or <30min/week) mobile phone use were calculated, as compared to operator data. For users of one mobile phone, agreement was fair for call frequency (κ=0.35, 95% CI: 0.35, 0.36) and moderate for call duration (κ=0.50, 95% CI: 0.49, 0.50). Self-reported low call frequency and duration demonstrated high sensitivity (87% and 76% respectively), but for high call frequency and duration sensitivity was lower (38% and 56% respectively), reflecting a tendency for greater underestimation than overestimation. Validity of self-reported mobile phone use was lower in women, younger age groups and those reporting symptoms during/shortly after using a mobile phone. This study highlights the ongoing value of using self-report data to measure mobile phone use. Furthermore, compared to continuous scale estimates used by previous studies, categorical response options used in COSMOS appear to improve validity considerably, most likely by preventing unrealistically high estimates from being reported

Decadal-timescale estuarine geomorphic change under future scenarios of climate and sediment supply

© The Authors, 2009. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Estuaries and Coasts 33 (2010): 15-29, doi:10.1007/s12237-009-9244-y.Future estuarine geomorphic change, in response to climate change, sea-level rise, and watershed sediment supply, may govern ecological function, navigation, and water quality. We estimated geomorphic changes in Suisun Bay, CA, under four scenarios using a tidal-timescale hydrodynamic/sediment transport model. Computational expense and data needs were reduced using the morphological hydrograph concept and the morphological acceleration factor. The four scenarios included (1) present-day conditions; (2) sea-level rise and freshwater flow changes of 2030; (3) sea-level rise and decreased watershed sediment supply of 2030; and (4) sea-level rise, freshwater flow changes, and decreased watershed sediment supply of 2030. Sea-level rise increased water levels thereby reducing wave-induced bottom shear stress and sediment redistribution during the wind-wave season. Decreased watershed sediment supply reduced net deposition within the estuary, while minor changes in freshwater flow timing and magnitude induced the smallest overall effect. In all future scenarios, net deposition in the entire estuary and in the shallowest areas did not keep pace with sea-level rise, suggesting that intertidal and wetland areas may struggle to maintain elevation. Tidal-timescale simulations using future conditions were also used to infer changes in optical depth: though sea-level rise acts to decrease mean light irradiance, decreased suspended-sediment concentrations increase irradiance, yielding small changes in optical depth. The modeling results also assisted with the development of a dimensionless estuarine geomorphic number representing the ratio of potential sediment import forces to sediment export forces; we found the number to be linearly related to relative geomorphic change in Suisun Bay. The methods implemented here are widely applicable to evaluating future scenarios of estuarine change over decadal timescales.This study was supported by the US Geological Survey’s Priority Ecosystems Science program, CALFED Bay/ Delta Program, and the University of California Center for Water Resources

How to improve medical education website design

<p>Abstract</p> <p>Background</p> <p>The Internet provides a means of disseminating medical education curricula, allowing institutions to share educational resources. Much of what is published online is poorly planned, does not meet learners' needs, or is out of date.</p> <p>Discussion</p> <p>Applying principles of curriculum development, adult learning theory and educational website design may result in improved online educational resources. Key steps in developing and implementing an education website include: 1) Follow established principles of curriculum development; 2) Perform a needs assessment and repeat the needs assessment regularly after curriculum implementation; 3) Include in the needs assessment targeted learners, educators, institutions, and society; 4) Use principles of adult learning and behavioral theory when developing content and website function; 5) Design the website and curriculum to demonstrate educational effectiveness at an individual and programmatic level; 6) Include a mechanism for sustaining website operations and updating content over a long period of time.</p> <p>Summary</p> <p>Interactive, online education programs are effective for medical training, but require planning, implementation, and maintenance that follow established principles of curriculum development, adult learning, and behavioral theory.</p

Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aβ-Induced Neurodegeneration and Synaptic Impairment

The p75 neurotrophin receptor (p75NTR) is expressed by neurons particularly vulnerable in Alzheimer's disease (AD). We tested the hypothesis that non-peptide, small molecule p75NTR ligands found to promote survival signaling might prevent Aβ-induced degeneration and synaptic dysfunction. These ligands inhibited Aβ-induced neuritic dystrophy, death of cultured neurons and Aβ-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Aβ-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3β and c-Jun, and tau phosphorylation, and prevented Aβ-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked Aβ-induced hippocampal LTP impairment. These studies support an extensive intersection between p75NTR signaling and Aβ pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Aβ-induced neuronal dystrophy and death