Highly stable, ligand-clustered “patchy” micelle nanocarriers for systemic tumor targeting

A novel linear-dendritic block copolymer has been synthesized and evaluated for targeted delivery. The use of the dendron as the micellar exterior block in this architecture allows the presentation of a relatively small quantity of ligands in clusters for enhanced targeting, thus maintaining a long circulation time of these “patchy” micelles. The polypeptide linear hydrophobic block drives formation of micelles that carry core-loaded drugs, and their unique design gives them extremely high stability in vivo. We have found that these systems lead to extended time periods of increased accumulation in the tumor (up to 5 days) compared with nontargeted vehicles. We also demonstrate a fourfold increase in efficacy of paclitaxel when delivered in the targeted nanoparticle systems, while significantly decreasing in vivo toxicity of the chemotherapy treatment.National Institute for Biomedical Imaging and Bioengineering (U.S.)National Cancer Institute (U.S.) (R01EB008082-01A2

The Prismatic Effect on Stereoacuity in Intermittent Exotropia

PURPOSE: To evaluate the effect of acrylic refractive prism and Fresnel membrane prism on stereoacuity in intermittent exotropia. MATERIALS AND METHODS: Stereoacuities of fifty-two patients (mean age, 12.4 years; range 6 to 45 years) with intermittent exotropia were measured using the Titmus and TNO stereotests, while they wore prisms of varying power on nonfixating eye or evenly on each eye. RESULTS: Stereoacuities were significantly reduced with increasing prism power for both prisms, ranging from 8 to 25 prism dipotres. The effects on stereoacuity in single acrylic prism and single Fresnel prism were similar, whereas spilt Fresnel prisms reduced stereoacuity more than spilt acrylic prisms. Spilt prisms were found to have much less effect on stereoacuity than single prisms for both acrylic and Fresnel prisms. CONCLUSION: The use of acrylic refractive prism shared evenly on each eye would be optimal method to minimize the reduction of stereoacuity during the prismatic therapy for intermittent exotropia.ope

Smokers' recall of Australian graphic cigarette packet warnings & awareness of associated health effects, 2005-2008

Extent: 11p.Background: In 2006, Australia introduced graphic cigarette packet warnings. The new warnings include one of 14 pictures, many depicting tobacco-related pathology. The warnings were introduced in two sets; Set A in March and Set B from November. This study explores their impact on smokers’ beliefs about smoking related illnesses. This study also examines the varying impact of different warnings, to see whether warnings with visceral images have greater impact on smokers’ beliefs than other images. Methods: Representative samples of South Australian smokers were interviewed in four independent cross-sectional omnibus surveys; in 2005 (n = 504), 2006 (n = 525), 2007 (n = 414) and 2008 (n = 464). Results: Unprompted recall of new graphic cigarette warnings was high in the months following their introduction, demonstrating that smokers’ had been exposed to them. Smokers also demonstrated an increase in awareness about smoking-related diseases specific to the warning messages. Warnings that conveyed new information and had emotive images demonstrated greater impact on recall and smokers’ beliefs than more familiar information and less emotive images. Conclusions: Overall graphic pack warnings have had the intended impact on smokers. Some have greater impact than others. The implications for policy makers in countries introducing similar warnings are that fresh messaging and visceral images have the greatest impact.Caroline L Miller, Pascale G Quester, David J Hill and Janet E Hille

Association of Kawasaki disease with tropospheric wind patterns

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Participants' perceptions of a lifestyle approach to promoting physical activity: targeting deprived communities in Kingston-upon-Hull.

BACKGROUND: The health benefits of an active lifestyle have been extensively documented and generally accepted. In the UK, declining physical activity levels are a major contributing factor to a number of public health concerns such as obesity and coronary heart disease. Clearly, there is an urgent need to support people in developing sustainable active lifestyles. In 2003, a new lifestyle-based physical activity service called Active Lifestyles (AL) was set up in Kingston-upon-Hull to help local residents to become more active and develop healthier lifestyles. The service targeted the most deprived communities in the city. The aim of the study was to explore participants' perceptions of the operation and effectiveness of the AL service. METHODS: Five focus groups were conducted in community centres and offices in the health promotion service in Kingston-upon-Hull. Sixteen white adult males (n = 5) and females (n = 11) participated in the study. Ages ranged from 15-73 years (mean age = 53 years). Data were analysed using a content analysis technique based on the 'framework' approach. RESULTS: Three broad themes emerged from the focus groups; the referral process; operational aspects of the AL service; and perceived benefits of the service. Overall, participants were extremely positive about the AL service. Many reported increased activity levels, modified eating habits, and enhanced awareness and education regarding healthier living. Most participants reported that local awareness of the AL service was low and greater promotion was required so more people could benefit. The success of the service was highly dependent upon the qualities and approach of the AL advisor. CONCLUSION: The service appears to have filled a gap in service provision since it offered support to the most sedentary, older, unfit and overweight individuals, many of whom live in the most deprived parts of Kingston-upon-Hull. Traditional exercise referral schemes that focus solely on facility-based exercise should be broadened to encompass everyday lifestyle activity, where referral to a gym or exercise facility is just one of a number of physical activity options

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability