Mathematical Models for Estimating the Risk of vCJD Transmission

We present two different simple models for vCJD transmission by blood transfusion. Both models indicate that transfusions alone are unlikely to cause more than a few infections, unless the number of primary cases increases. To improve our models, future work should pursue data collection, empirical estimation of the model parameters, and examination of the underlying assumptions of our frameworks. Further improvements could also include examining susceptibility to vCJD infection by age group and iatrogenic infections introduced through surgical instruments. Regarding the latter, it may be worthwhile to conduct experiments to quantify the transmission of prions from an infected surgical instrument after repeated sterilization procedures

ESR study of the single-ion anisotropy in the pyrochlore antiferromagnet Gd2Sn2O7

Single-ion anisotropy is of importance for the magnetic ordering of the frustrated pyrochlore antiferromagnets Gd2Ti2O7 and Gd2Sn2O7. The anisotropy parameters for the Gd2Sn2O7 were measured using the electron spin resonance (ESR) technique. The anisotropy was found to be of the easy plane type, with the main constant D=140mK. This value is 35% smaller than the value of the corresponding anisotropy constant in the related compound Gd2Ti2O7.Comment: 8 pages, 3 figure

Characterization of the cytotoxic effects of the combination of cisplatin and flavanol (-)-epicatechin on human lung cancer cell line A549. An isobolographic approach

Background: Among malignancies, lung cancer is a leading cause of death. Platinum-based therapeutic compounds used to treat lung cancer have not been able to increase the survival of patients and such compounds have a high incidence of adverse and toxic effects. It has been proposed that flavonoids such as catechins may significantly reduce the risk of developing cancer, alongside with other health benefits. The aim of this work was to determine the effect of (-)-epicatechin, the main flavanol found in cocoa, on the proliferation of the lung non-small cell adenocarcinoma cancer cell line A549, and to determine its effects when added simultaneously with cisplatin. Materials and Methods: Concentration-response curves for cisplatin and epicatechin were obtained, inhibitory concentrations calculated and an isobolographic analysis was then performed. Results: We found that epicatechin has a concentration-dependent inhibitory effect on proliferation of tumor cells and the isobolographic analysis reveals that the effect of its combination with cisplatin is synergistic. It was also observed that epicatechin promotes cell death by apoptosis. Conclusions: Epicatechin might be considered for future studies to explore its possible use as coadjuvant in cisplatin-based treatments

Early Science with the Large Millimetre Telescope: Molecules in the Extreme Outflow of a proto-Planetary Nebula

Extremely high velocity emission likely related to jets is known to occur in some proto-Planetary Nebulae. However, the molecular complexity of this kinematic component is largely unknown. We observed the known extreme outflow from the proto-Planetary Nebula IRAS 16342-3814, a prototype water fountain, in the full frequency range from 73 to 111 GHz with the RSR receiver on the Large Millimetre Telescope. We detected the molecules SiO, HCN, SO, and $^{13}$CO. All molecular transitions, with the exception of the latter are detected for the first time in this source, and all present emission with velocities up to a few hundred km s$^{-1}$. IRAS 16342-3814 is therefore the only source of this kind presenting extreme outflow activity simultaneously in all these molecules, with SO and SiO emission showing the highest velocities found of these species in proto-Planetary Nebulae. To be confirmed is a tentative weak SO component with a FWHM $\sim$ 700 km s$^{-1}$. The extreme outflow gas consists of dense gas (n$_{\rm H_2} >$ 10$^{4.8}$--10$^{5.7}$ cm$^{-3}$), with a mass larger than $\sim$ 0.02--0.15 M$_{\odot}$. The relatively high abundances of SiO and SO may be an indication of an oxygen-rich extreme high velocity gas.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society Letter

EVIDENT 3 Study: A randomized, controlled clinical trial to reduce inactivity and caloric intake in sedentary and overweight or obese people using a smartphone application: Study protocol

Introduction: Mobile technology, when included within multicomponent interventions, could contribute to more effective weight loss. The objective of this project is to assess the impact of adding the use of the EVIDENT 3 application, designed to promote healthy living habits, to traditional modification strategies employed for weight loss. Other targeted behaviors (walking, caloric-intake, sitting time) and outcomes (quality of life, inflammatory markers, measurements of arterial aging) will also be evaluated. Methods: Randomized, multicentre clinical trial with 2 parallel groups. The study will be conducted in the primary care setting and will include 700 subjects 20 to 65 years, with a body mass index (27.5-40kg/m2), who are clinically classified as sedentary. The primary outcome will be weight loss. Secondary outcomes will include change in walking (steps/d), sitting time (min/wk), caloric intake (kcal/d), quality of life, arterial aging (augmentation index), and pro-inflammatory marker levels. Outcomes will be measured at baseline, after 3 months, and after 1 year. Participants will be randomly assigned to either the intervention group (IG) or the control group (CG). Both groups will receive the traditional primary care lifestyle counseling prior to randomization. The subjects in the IG will be lent a smartphone and a smartband for a 3-month period, corresponding to the length of the intervention. The EVIDENT 3 application integrates the information collected by the smartband on physical activity and the self-reported information by participants on daily food intake. Using this information, the application generates recommendations and personalized goals for weight loss. Discussion: There is a great diversity in the applications used obtaining different results on lifestyle improvement and weight loss. The populations studied are not homogeneous and generate different results. The results of this study will help our understanding of the efficacy of new technologies, combined with traditional counseling, towards reducing obesity and enabling healthier lifestyles. Ethicsanddissemination: The study was approved by the Clinical Research Ethics Committee of the Health Area of Salamanca ("CREC of Health Area of Salamanca") on April 2016. A SPIRIT checklist is available for this protocol. The trial was registered in ClinicalTrials.gov provided by the US National Library of Medicine-number NCT03175614

Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function

Abstract Background: Leptin and nitric oxide (NO) on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact of the absence of the inducible NO synthase (iNOS) gene in the regulation of energy balance in ob/ob mice. Methods and Findings: Double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes were generated, and the expression of molecules involved in the control of brown fat cell function was analyzed by real-time PCR, western-blot and immunohistochemistry. Twelve week-old DBKO mice exhibited reduced body weight (p,0.05), decreased amounts of total fat pads (p,0.05), lower food efficiency rates (p,0.05) and higher rectal temperature (p,0.05) than ob/ob mice. Ablation of iNOS also improved the carbohydrate and lipid metabolism of ob/ob mice. DBKO showed a marked reduction in the size of brown adipocytes compared to ob/ob mutants. In this sense, in comparison to ob/ob mice, DBKO rodents showed an increase in the expression of PR domain containing 16 (Prdm16), a transcriptional regulator of brown adipogenesis. Moreover, iNOS deletion enhanced the expression of mitochondria-related proteins, such as peroxisome proliferatoractivated receptor c coactivator-1 a (Pgc-1a), sirtuin-1 (Sirt-1) and sirtuin-3 (Sirt-3). Accordingly, mitochondrial uncoupling proteins 1 and 3 (Ucp-1 and Ucp-3) were upregulated in brown adipose tissue (BAT) of DBKO mice as compared to ob/ob rodents. Conclusion: Ablation of iNOS improved the energy balance of ob/ob mice by decreasing food efficiency through an increase in thermogenesis. These effects may be mediated, in part, through the recovery of the BAT phenotype and brown fat cell function improvement