The interaction of carbon nanotubes with an invitro blood-brain barrier model and mouse brain in vivo

Under a Creative Commons license.-- et al.Carbon nanotubes (CNTs) are a novel nanocarriers with interesting physical and chemical properties. Here we investigate the ability of amino-functionalized multi-walled carbon nanotubes (MWNTs-NH3+) to cross the Blood-Brain Barrier (BBB) in vitro using a co-culture BBB model comprising primary porcine brain endothelial cells (PBEC) and primary rat astrocytes, and in vivo following a systemic administration of radiolabelled f-MWNTs. Transmission Electron microscopy (TEM) confirmed that MWNTs-NH3+ crossed the PBEC monolayer via energy-dependent transcytosis. MWNTs-NH3+ were observed within endocytic vesicles and multi-vesicular bodies after 4 and 24 h. A complete crossing of the in vitro BBB model was observed after 48 h, which was further confirmed by the presence of MWNTs-NH3+ within the astrocytes. MWNT-NH3+ that crossed the PBEC layer was quantitatively assessed using radioactive tracers. A maximum transport of 13.0 ± 1.1% after 72 h was achieved using the co-culture model. f-MWNT exhibited significant brain uptake (1.1 ± 0.3% injected dose/g) at 5 min after intravenous injection in mice, after whole body perfusion with heparinized saline. Capillary depletion confirmed presence of f-MWNT in both brain capillaries and parenchyma fractions. These results could pave the way for use of CNTs as nanocarriers for delivery of drugs and biologics to the brain, after systemic administration.KAJ acknowledges funding from Biotechnology and Biological Sciences Research Council (BB/J008656/1) and Worldwide Cancer Research (12-1054). KAJ, EP and BB acknowledge the EU FP7-ITN Marie-Curie Network programme RADDEL (290023). HK was sponsored by the Atomic Energy Commission of Syria. EP is enrolled in the UAB PhD program. KAJ thanks the members of the EU COST actions TD1004 (Theranostics Imaging and Therapy: An Action to Develop Novel Nanosized Systems for Imaging-Guided Drug Delivery and Biological Processes) for sponsoring HK's research stay at the ICN2 for the electron microscopy studies. ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295). Open Access funded by Biotechnology and Biological Sciences Research CouncilPeer Reviewe

Sociobehavioural Research Methods for the Introduction of Vaccines in the Diseases of the Most Impoverished Programme

Participation in vaccination campaigns worldwide, particularly the Expanded Programme on Immunization, has increased significantly in recent years. However, there remain multiple and integrated behavioural, sociocultural and political-economic barriers to vaccination. The Diseases of the Most Impoverished (DOMI) Programme has undertaken shigellosis disease-burden studies and oral cholera and typhoid Vi polysaccharide vaccine trials in seven Asian countries. As part of these projects, sociobehavioural studies have been undertaken to determine the potential demand for vaccines for these diseases and the obstacles and enabling factors that may affect acceptance, delivery, and use of vaccines. A theoretical model of acceptance of vaccination and a triangulation of qualitative and quantitative methods have been used for fully elucidating the range of issues relating to vaccination for shigellosis, cholera, and typhoid fever. In this paper, the theoretical and methodological basis of the DOMI projects has been reviewed in a context of current sociobehavioural research on the acceptability and desirability of vaccination

Triangle-Free Penny Graphs: Degeneracy, Choosability, and Edge Count

We show that triangle-free penny graphs have degeneracy at most two, list coloring number (choosability) at most three, diameter $D=\Omega(\sqrt n)$, and at most $\min\bigl(2n-\Omega(\sqrt n),2n-D-2\bigr)$ edges.Comment: 10 pages, 2 figures. To appear at the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Pixel and Voxel Representations of Graphs

We study contact representations for graphs, which we call pixel representations in 2D and voxel representations in 3D. Our representations are based on the unit square grid whose cells we call pixels in 2D and voxels in 3D. Two pixels are adjacent if they share an edge, two voxels if they share a face. We call a connected set of pixels or voxels a blob. Given a graph, we represent its vertices by disjoint blobs such that two blobs contain adjacent pixels or voxels if and only if the corresponding vertices are adjacent. We are interested in the size of a representation, which is the number of pixels or voxels it consists of. We first show that finding minimum-size representations is NP-complete. Then, we bound representation sizes needed for certain graph classes. In 2D, we show that, for $k$-outerplanar graphs with $n$ vertices, $\Theta(kn)$ pixels are always sufficient and sometimes necessary. In particular, outerplanar graphs can be represented with a linear number of pixels, whereas general planar graphs sometimes need a quadratic number. In 3D, $\Theta(n^2)$ voxels are always sufficient and sometimes necessary for any $n$-vertex graph. We improve this bound to $\Theta(n\cdot \tau)$ for graphs of treewidth $\tau$ and to $O((g+1)^2n\log^2n)$ for graphs of genus $g$. In particular, planar graphs admit representations with $O(n\log^2n)$ voxels

Adults\u27 perceived prevalence of enteric fever predicts laboratory-validated incidence of typhoid fever in children

This study was undertaken to develop a model to predict the incidence of typhoid in children based on adults’ perception of prevalence of enteric fever in the wider community. Typhoid cases among children, aged 5-15 years, from epidemic regions in five Asian countries were confirmed with a positive Salmonella Typhi culture of the blood sample. Estimates of the prevalence of enteric fever were obtained from random samples of adults in the same study sites. Regression models were used for establishing the prediction equation. The percentages of enteric fever reported by adults and cases of typhoid incidence per 100,000, detected through blood culture were 4.7 and 24.18 for Viet Nam, 3.8 and 29.20 for China, 26.3 and 180.33 for Indonesia, 66.0 and 454.15 for India, and 52.7 and 407.18 for Pakistan respectively. An established prediction equation was: incidence of typhoid (1/100,000= −2.6946 + 7.2296 × reported prevalence of enteric fever (%) (F=31.7, p2=0.992). Using adults’ perception of prevalence of disease as the basis for estimating its incidence in children provides a cost-effective behavioural epidemiologic method to facilitate prevention and control of the disease

Design of antibody-functionalized carbon nanotubes filled with radioactivable metals towards a targeted anticancer therapy

In the present work we have devised the synthesis of a novel promising carbon nanotube carrier for the targeted delivery of radioactivity, through a combination of endohedral and exohedral functionalization. Steam-purified single-walled carbon nanotubes (SWCNTs) have been initially filled with radioactive analogues (i.e. metal halides) and sealed by high temperature treatment, affording closed-ended CNTs with the filling material confined in the inner cavity. The external functionalization of these filled CNTs was then achieved by nitrene cycloaddition and followed by the derivatization with a monoclonal antibody (Cetuximab) targeting the epidermal growth factor receptor (EGFR), overexpressed by several cancer cells. The targeting efficiency of the so-obtained conjugate was evaluated by immunostaining with a secondary antibody and by incubation of the CNTs with EGFR positive cells (U87-EGFR+), followed by flow cytometry, confocal microscopy or elemental analyses. We demonstrated that our filled and functionalized CNTs can internalize more efficiently in EGFR positive cancer cells

Adults' Perceived Prevalence of Enteric Fever Predicts Laboratory-validated Incidence of Typhoid Fever in Children

This study was undertaken to develop a model to predict the incidence of typhoid in children based on adults' perception of prevalence of enteric fever in the wider community. Typhoid cases among children, aged 5-15 years, from epidemic regions in five Asian countries were confirmed with a positive Salmonella Typhi culture of the blood sample. Estimates of the prevalence of enteric fever were obtained from random samples of adults in the same study sites. Regression models were used for establishing the prediction equation. The percentages of enteric fever reported by adults and cases of typhoid incidence per 100,000, detected through blood culture were 4.7 and 24.18 for Viet Nam, 3.8 and 29.20 for China, 26.3 and 180.33 for Indonesia, 66.0 and 454.15 for India, and 52.7 and 407.18 for Pakistan respectively. An established prediction equation was: incidence of typhoid (1/100,000= -2.6946 + 7.2296 7 reported prevalence of enteric fever (%) (F=31.7, p<0.01; R2=0.992). Using adults' perception of prevalence of disease as the basis for estimating its incidence in children provides a cost-effective behavioural epidemiologic method to facilitate prevention and control of the disease

Oral cholera vaccine use in Zanzibar: socioeconomic and behavioural features affecting demand and acceptance

Cholera remains a serious public health problem in low-income countries despite efforts in the past to promote oral rehydration therapy as major treatment. In 2007, the majority of worldwide cases (94%) and deaths (99%) were reported from Africa. To improve cholera control efforts in addition to maintaining and improving existing water supply, sanitation and hygiene behaviour measures, the World Health Organization has recently started to consider the use of vaccines as an additional public health tool. To assess this new approach in endemic settings, a project was launched in Zanzibar to vaccinate 50,000 individuals living in communities at high risk of cholera with an oral two-dose vaccine (Dukoral). Immunisation programmes in low-income countries have suffered a reduced coverage or were even brought to a halt because of an ignorance of local realities. To ensure the success of vaccination campaigns, implementers have to consider community-held perceptions and behaviours regarding the infectious disease and the vaccine of interest. The main aim of this study is to provide advice to the Ministry of Health and Social Welfare of Zanzibar regarding routine introduction of an oral cholera vaccine from a socioeconomic and behavioural perspective as part of a long-term development for a sustained cholera prevention strategy. Qualitative and quantitative methods of health social science research will be applied on four stakeholder levels before and after the mass vaccination campaign. Rapid assessment individual interviews and focus groups will be used to describe cholera- and vaccine-related views of policy makers, health care professionals and community representatives. The cultural epidemiological approach will be employed on the individual household resident level in a repeated cross-sectional design to estimate determinants of anticipated and actual oral cholera vaccine acceptance. The study presented here is designed to inform about people's perceptions regarding cholera and about socioeconomic and behavioural factors determining anticipated and actual oral cholera vaccine acceptance in Zanzibar. Its pre- and post-intervention design using a mixed-methods approach on different stakeholder levels in communities at high risk of cholera outbreaks will ensure the collection of locally valid data relevant for public health action and planning