Weather, climate change and dengue in Mexico

Many studies have estimated empirical relationships between dengue, weather, and El Ni˜no in several regions of the world. Some of these studies used their model estimations to predict the potential impacts of climate change on the future distribution of dengue. Often, these studies have sidestepped elements that are key to the estimation of the effects of climate variables on dengue with statistical confidence. For example, they fail to incorporate covariates that may confound the empirical associations between dengue, weather, El Ni˜no, and climate undermining their model estimations. Additionally, several studies used nationally or supra-nationally aggregated data which remove the spatial variability in all variables making it difficult to detect complex associations between dengue and climate variables. Other studies were conducted in small geographical areas with the problem of having low numbers of disease cases posing problems for their analysis with statistical confidence. Here, we used the most comprehensive dengue-related datasets analysed to date and several statistical methods to investigate the effects of weather, climate, and El Ni˜no on dengue incidence. We demonstrate that such effects are robust to the confounding effects of socioeconomic development and other non-climatic factors such as seasonal trends and inter-annual variability. Our results reveal that the effects weather and El Ni˜no are significantly heterogeneous between provinces influenced by the underlying climate. With the exception of access to piped water, we could not identify significant effects of socioeconomic status on dengue occurrence. This result is likely related to human behaviour or the lack of protective measures against mosquitoes. We used our model estimations to project the potential impacts of climate change on dengue incidence by 2030, 2050 and 2080 with greater statistical confidence than previous studies. Our projections indicate that climate change is likely to increase dengue incidence mainly in already endemic areas

Peroxisome proliferator-activated receptor α-independent peroxisome proliferation

Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor α (PPARα) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPARα-independent peroxisome proliferation, fenofibrate treatment was used, which was expected to significantly enhance PPARα dependence in the assay system. Surprisingly, a novel type of PPARα-independent peroxisome proliferation and enlargement was uncovered in PPARα-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11α, might be associated with the PPARα-independent peroxisome proliferation at least in part.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 346(4): 1307-1311(2006)journal articl

Trends in alcohol-related injury admissions in adolescents in Western Australia and England: population-based cohort study

BACKGROUND: Alcohol-related harm in young people is now a global health priority. We examined trends in hospital admissions for alcohol-related injuries for adolescents in Western Australia (WA) and in England, identified groups most at risk and determined causes of injuries. METHODS: Annual incidence rates for alcohol-related injury rates were calculated using population-level hospital admissions data for WA and England. We compared trends in different types of alcohol-related injury by age and gender. RESULTS: Despite a decrease in the overall rate of injury admissions for people aged 13-17 years in WA, alcohol-related injuries have increased significantly from 1990 to 2009 (from 8 to 12 per 10 000). Conversely, alcohol-related injury rates have declined in England since 2007. In England, self-harm is the most frequently recorded cause of alcohol-related injury. In WA, unintentional injury is most common; however, violence-related harm is increasing for boys and girls. CONCLUSION: Alcohol-related harm of sufficient severity to require hospital admission is increasing among adolescents in WA. Declining trends in England suggest that this trend is not inevitable or irreversible. More needs to be done to address alcohol-related harm, and on-going monitoring is required to assess the effectiveness of strategies

Polyenephosphatidylcholine prevents alcoholic liver disease in PPARα-null mice through attenuation of increases in oxidative stress

Background/Aims: Alcoholic liver disease (ALD) is one of the leading causes of cirrhosis and yet efficient therapeutic strategies are lacking. Polyenephosphatidylcholine (PPC), a major component of essential phospholipids, prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains uncertain. We aimed to explore the effects of PPC on ALD using ethanol-fed peroxisome proliferator-activated receptor α (Ppara)-null mice, showing several similarities to human ALD. Methods: Male wild-type and Ppara-null mice were pair-fed a Lieber-DeCarli control or 4% ethanol-containing diet with or without PPC (30 mg/kg/day) for 6 months. Results: PPC significantly ameliorated ethanol-induced hepatocyte damage and hepatitis in Ppara-null mice. These effects were likely a consequence of decreased oxidative stress through down-regulation of reactive oxygen species (ROS)-generating enzymes, including cytochrome P450 2E1, acyl-CoA oxidase, and NADPH oxidases, in addition to restoration of increases in Toll-like receptor 4 and CD14. PPC also decreased Bax and truncated Bid, thus inhibiting apoptosis. Furthermore, PPC suppressed increases in transforming growth factor-β1 expression and hepatic stellate cell activation, which retarded hepatic fibrogenesis. Conclusions: PPC exhibited anti-inflammatory, anti-apoptotic, and anti-fibrotic effects on ALD as a result of inhibition of the overexpression of ROS-generating enzymes. Our results demonstrate detailed molecular mechanisms of the anti-oxidant action of PPC.ArticleJournal of Hepatology 50(6): 1236-1246(2009)journal articl

Smart Nanoparticles as Advanced Anti-Akt Kinase Delivery Systems for Pancreatic Cancer Therapy

Pancreatic cancer is one of the deadliest cancers partly due to late diagnosis, poor drug delivery to the target site, and acquired resistance to therapy. Therefore, more effective therapies are urgently needed to improve the outcome of patients. In this work, we have tested self-assembling genetically engineered polymeric nanoparticles formed by elastin-like recombinamers (ELRs), carrying a small peptide inhibitor of the protein kinase Akt, in both PANC-1 and patient-derived pancreatic cancer cells (PDX models). Nanoparticle cell uptake was measured by flow cytometry, and subcellular localization was determined by confocal microscopy, which showed a lysosomal localization of these nanoparticles. Furthermore, metabolic activity and cell viability were significantly reduced after incubation with nanoparticles carrying the Akt inhibitor in a time- and dose-dependent fashion. Self-assembling 73 ± 3.2 nm size nanoparticles inhibited phosphorylation and consequent activation of Akt protein, blocked the NF-κB signaling pathway, and triggered caspase 3-mediated apoptosis. Furthermore, in vivo assays showed that ELR-based nanoparticles were suitable devices for drug delivery purposes with long circulating time and minimum toxicity. Hence, the use of these smart nanoparticles could lead to the development of more effective treatment options for pancreatic cancer based on the inhibition of Akt

Monovinyl sulfone beta-cyclodextrin. A flexible drug carrier system

Cyclodextrins have been conjugated to target various receptors and have also been functionalized with carbohydrates for targeting specific organs. However, this approach is based on a rigid design that implies the ad hoc synthesis of each cyclodextrin-targeting agent conjugate. We hypothesized that: 1) a modular design that decouples the carrier function from the targeting function leads to a flexible system, 2) combining the reactivity of the vinyl sulfone group toward biomolecules that act as targeting agents with the ability of cyclodextrin to form complexes with a wide range of drugs may yield a versatile system that allows the targeting of different organs with different drugs, and 3) the higher reactivity of histidine residues toward the vinyl sulfone group can be exploited to couple the cyclodextrin to the targeting system with a degree of regioselectivity. As a proof of concept, we synthesized a monovinyl sulfone beta-cyclodextrin (module responsible for the payload), which, after coupling to recombinant antibody fragments raised against Trypanosoma brucei (module responsible for targeting) and loading with nitrofurazone (module responsible for therapeutic action) resulted in an effective delivery system that targets the surface of the parasites and shows trypanocidal activity

On the minimal thermal habitability conditions in low income dwellings in Spain for a new definition of fuel poverty

Fuel poverty can be defined as “the inability to afford adequate warmth in the home”. The concept was firstly developed due to health risks related to cold among low income households. However, in the last few decades, especially since the summer heat wave of 2003 that caused 35,000 deaths across Europe, a lot of research has been conducted about the health risks related to high temperatures. Along with advances in knowledge related to the health risks associated with inadequate temperatures, several directives of the European Commission related to energy regulation urge Member States to develop their own fuel poverty definitions. This need of a methodological development for new definitions poses several questions. First, what should be the temperature thresholds for the overheated season? But, furthermore, are existing temperature baselines adequate for the Spanish context and climate? This paper presents a preliminary approach to define these new temperature thresholds for the Spanish context through the adaptive comfort model criteria. For that purpose, a statistically representative dwelling building typology of vulnerable household spaces was used to analyze indoor thermal temperatures and hence, to establish minimal energy requirements so as to achieve minimal habitability conditions

Numerical Modeling of the Internal Temperature in the Mammary Gland

The microwave thermometry method for the diagnosis of breast cancer is based on an analysis of the internal temperature distribution.This paper is devoted to the construction of a mathematical model for increasing the accuracy of measuring the internal temperature of mammary glands, which are regarded as a complex combination of several components, such as fat tissue, muscle tissue, milk lobules, skin, blood flows, tumor tissue. Each of these biocomponents is determined by its own set of physical parameters. Our numerical model is designed to calculate the spatial distributions of the electric microwave field and the temperature inside the biological tissue. We compare the numerical simulations results to the real medical measurements of the internal temperature.Comment: 8 pages, 4 figure

Testing matter effects in propagation of atmospheric and long-baseline neutrinos

We quantify our current knowledge of the size and flavor structure of the matter effects in the evolution of atmospheric and long-baseline neutrinos based solely on the analysis of the corresponding neutrino data. To this aim we generalize the matter potential of the Standard Model by rescaling its strength, rotating it away from the e-e sector, and rephasing it with respect to the vacuum term. This phenomenological parametrization can be easily translated in terms of non-standard neutrino interactions in matter. We show that in the most general case, the strength of the potential cannot be determined solely by atmospheric and long-baseline data. However its flavor composition is very much constrained and the present determination of the neutrino masses and mixing is robust under its presence. We also present an update of the constraints arising from this analysis in the particular case in which no potential is present in the e-mu and e-tau sectors. Finally we quantify to what degree in this scenario it is possible to alleviate the tension between the oscillation results for neutrinos and antineutrinos in the MINOS experiment and show the relevance of the high energy part of the spectrum measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included. Accepted for publication in JHE

Coupling of individual quantum emitters to channel plasmons.

Efficient light-matter interaction lies at the heart of many emerging technologies that seek on-chip integration of solid-state photonic systems. Plasmonic waveguides, which guide the radiation in the form of strongly confined surface plasmon-polariton modes, represent a promising solution to manipulate single photons in coplanar architectures with unprecedented small footprints. Here we demonstrate coupling of the emission from a single quantum emitter to the channel plasmon polaritons supported by a V-groove plasmonic waveguide. Extensive theoretical simulations enable us to determine the position and orientation of the quantum emitter for optimum coupling. Concomitantly with these predictions, we demonstrate experimentally that 42% of a single nitrogen-vacancy centre emission efficiently couples into the supported modes of the V-groove. This work paves the way towards practical realization of efficient and long distance transfer of energy for integrated solid-state quantum systems.E.B.-U., R.M., M.G. and R.Q. acknowledge the European Community’s Seventh Framework Programme (grant ERC- Plasmolight; no. 259196) and Fundació privada CELLEX. E.B.-U. acknowledges support of the FPI fellowship from the Spanish MICINN. R.M. acknowledges support of Marie Curie and NEST fellowships. C.G.-B. and F.J.G.-V. acknowledge the European Research Council (ERC-2011-AdG, Proposal No. 290981). C.G.-B., E.M., and F.J.G.-V. acknowledge the Spanish MINECO (Contract No. MAT2011-28581-C02-01). C.G.-B. acknowledges support of the FPU fellowship from the Spanish MECD. I.P.R., T.H. and S.I.B. acknowledge financial support for this work from the Danish Council for Independent Research (the FTP project ANAP, Contract No. 09-072949) and from the European Research Council, Grant No. 341054 (PLAQNAP). Y.A. acknowledges the support of RYC-2011-08471 fellowship from MICINN. We thank Luis Martin-Moreno and Cesar E. García for fruitful discussions, Jana M. Say and Louise J. Brown for providing the ND solution, and Ioannis Tsioutsios for support with the AFM manipulation technique.This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150807/ncomms8883/full/ncomms8883.html