Desalination and water security in Southeastern Spain

The Segura Hydrographic Demarcation (DHS), in Southeastern Spain, is an area of hydric deficit caused by low and irregular rainfall and a dense population. In this region water scarcity is a burning issue that polarizes society for or against different models of ensuring water supply. Given the current demand for water throughout Spain, desalination has been used to increase water supply, and as insurance against drought. Ten seawater desalination plants and hundreds of brackish aquifer desalination plants treat water in the Southeast of the Iberian Peninsula, both for human consumption and for irrigation, contributing to economic, energetic, processual and economic aspects of territorial organization in the Southeast of Spain. This article reviews debates over desalination, water transfers, and the best way to meet water demands in that region. While desalination allows an increase in water supply, dependence on that source increases energy costs and may lead to mistaken assumptions among users about water scarcity and availabilityLa Demarcación Hidrográfica del Segura (DHS) comprende un área hídricamente deficitaria motivada por una reducida e irregular pluviometría y una intensa ocupación del territorio, en la que el recurso agua ha sido y es un bien limitado y muy preciado desde la antigüedad, y es un candente asunto de la actualidad que polariza a la sociedad a favor o en contra de un modelo u otro de abastecimiento. Ante las actuales demandas de este recurso, se hace necesario recurrir a la desalación para un incremento de la oferta hídrica que actúa como un seguro ante situaciones de sequía en España. Un total de diez plantas desaladoras y cientos de desalobradoras suministran agua desalada procedente del mar o de acuíferos salobres en el Sureste de la Península Ibérica, tanto para consumo humano como para la irrigación de los fértiles campos, aportando su idiosincrasia económica, energética, procesual y de ordenación territoria

Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-κB), considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-κB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone, and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p., for 18 days. Reduced and oxidized forms of glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) activity and glutamate were determined in cerebellar homogenates. NF-κB activity, CD68, and GFAP expression were determined. Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-κB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations. Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction

A sensitive nanosensor for the in situ detection of the cannibal drug

[EN] A bio-inspired nanodevice for the selective and sensitive fluorogenic detection of 3,4- methylenedioxypyrovalerone (MDPV), usually known as Cannibal drug, is reported. The sensing nanodevice is based on mesoporous silica nanoparticles (MSNs), loaded with a fluorescent reporter (rhodamine B) and functionalized on their external surface with a dopamine derivative (3), which specifically interacts with the recombinant human dopamine transporter (DAT), capping the pores. In the presence of MDPV, DAT detaches from the MSNs consequently causing rhodamine B release and allowing drug detection. The nanosensor shows a detection limit of 5.2 µM and it is able to detect the MDPV drug both in saliva and blood plasma samples.The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. M.A. thanks her postdoctoral fellowship (PAID -10-17). The authors also thank the Electron Microscopy Service at the UPV for support.Garrido-García, EM.; Alfonso-Navarro, M.; Díaz De Greñu-Puertas, B.; Marcos Martínez, MD.; Costero, AM.; Gil Grau, S.; Sancenón Galarza, F.... (2020). A sensitive nanosensor for the in situ detection of the cannibal drug. ACS Sensors. 5(9):2966-2972. https://doi.org/10.1021/acssensors.0c01553S2966297259World drug report United Nations Office on Drugs and Crime (UNODC). Inform; 2019.European drug report Trends and Developments. European Monitoring Centre for Drugs and Drug Addition (EMCDDA). Inform; 2019.Zawilska, J. B., & Wojcieszak, J. (2013). Designer cathinones—An emerging class of novel recreational drugs. Forensic Science International, 231(1-3), 42-53. doi:10.1016/j.forsciint.2013.04.015Coppola, M., & Mondola, R. (2012). 3,4-Methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicology Letters, 208(1), 12-15. doi:10.1016/j.toxlet.2011.10.002Coppola, M., & Mondola, R. (2012). Synthetic cathinones: Chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as «bath salts» or «plant food». Toxicology Letters, 211(2), 144-149. doi:10.1016/j.toxlet.2012.03.009Oliver, C. F., Palamar, J. J., Salomone, A., Simmons, S. J., Philogene-Khalid, H. L., Stokes-McCloskey, N., & Rawls, S. M. (2018). Synthetic cathinone adulteration of illegal drugs. Psychopharmacology, 236(3), 869-879. doi:10.1007/s00213-018-5066-6Riley, A. L., Nelson, K. H., To, P., López-Arnau, R., Xu, P., Wang, D., … Hall, F. S. (2020). Abuse potential and toxicity of the synthetic cathinones (i.e., «Bath salts»). Neuroscience & Biobehavioral Reviews, 110, 150-173. doi:10.1016/j.neubiorev.2018.07.015Ibáñez, M., Pozo, Ó. J., Sancho, J. V., Orengo, T., Haro, G., & Hernández, F. (2015). Analytical strategy to investigate 3,4-methylenedioxypyrovalerone (MDPV) metabolites in consumers’ urine by high-resolution mass spectrometry. Analytical and Bioanalytical Chemistry, 408(1), 151-164. doi:10.1007/s00216-015-9088-1Colon-Perez, L. M., Pino, J. A., Saha, K., Pompilus, M., Kaplitz, S., Choudhury, N., … Febo, M. (2018). Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone. Neuropharmacology, 137, 178-193. doi:10.1016/j.neuropharm.2018.04.031Eshleman, A. J., Nagarajan, S., Wolfrum, K. M., Reed, J. F., Swanson, T. L., Nilsen, A., & Janowsky, A. (2018). Structure-activity relationships of bath salt components: substituted cathinones and benzofurans at biogenic amine transporters. Psychopharmacology, 236(3), 939-952. doi:10.1007/s00213-018-5059-5Glennon, R. A., & Young, R. (2016). Neurobiology of 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinovalerophenone (α-PVP). Brain Research Bulletin, 126, 111-126. doi:10.1016/j.brainresbull.2016.04.011Kraemer, M., Boehmer, A., Madea, B., & Maas, A. (2019). Death cases involving certain new psychoactive substances: A review of the literature. Forensic Science International, 298, 186-267. doi:10.1016/j.forsciint.2019.02.021Liveri, K., Constantinou, M. A., Afxentiou, M., & Kanari, P. (2016). A fatal intoxication related to MDPV and pentedrone combined with antipsychotic and antidepressant substances in Cyprus. Forensic Science International, 265, 160-165. doi:10.1016/j.forsciint.2016.02.017Marinetti, L. J., & Antonides, H. M. (2013). Analysis of Synthetic Cathinones Commonly Found in Bath Salts in Human Performance and Postmortem Toxicology: Method Development, Drug Distribution and Interpretation of Results. Journal of Analytical Toxicology, 37(3), 135-146. doi:10.1093/jat/bks136Freni, F., Bianco, S., Vignali, C., Groppi, A., Moretti, M., Osculati, A. M. M., & Morini, L. (2019). A multi-analyte LC–MS/MS method for screening and quantification of 16 synthetic cathinones in hair: Application to postmortem cases. Forensic Science International, 298, 115-120. doi:10.1016/j.forsciint.2019.02.036Peiró, M. de las N., Armenta, S., Garrigues, S., & de la Guardia, M. (2016). Determination of 3,4-methylenedioxypyrovalerone (MDPV) in oral and nasal fluids by ion mobility spectrometry. Analytical and Bioanalytical Chemistry, 408(12), 3265-3273. doi:10.1007/s00216-016-9395-1Cheng, S.-Y., Ng-A-Qui, T., Eng, B., & Ho, J. (2017). Detection of cathinone and mephedrone in plasma by LC-MS/MS using standard addition quantification technique. Journal of Analytical Science and Technology, 8(1). doi:10.1186/s40543-017-0128-7Glicksberg, L., Bryand, K., & Kerrigan, S. (2016). Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry. Journal of Chromatography B, 1035, 91-103. doi:10.1016/j.jchromb.2016.09.027Mercieca, G., Odoardi, S., Cassar, M., & Strano Rossi, S. (2018). Rapid and simple procedure for the determination of cathinones, amphetamine-like stimulants and other new psychoactive substances in blood and urine by GC–MS. Journal of Pharmaceutical and Biomedical Analysis, 149, 494-501. doi:10.1016/j.jpba.2017.11.024Gerace, E., Caneparo, D., Borio, F., Salomone, A., & Vincenti, M. (2019). Determination of several synthetic cathinones and an amphetamine‐like compound in urine by gas chromatography with mass spectrometry. Method validation and application to real cases. Journal of Separation Science, 42(8), 1577-1584. doi:10.1002/jssc.201801249Woźniak, M. K., Banaszkiewicz, L., Wiergowski, M., Tomczak, E., Kata, M., Szpiech, B., … Biziuk, M. (2019). Development and validation of a GC–MS/MS method for the determination of 11 amphetamines and 34 synthetic cathinones in whole blood. Forensic Toxicology, 38(1), 42-58. doi:10.1007/s11419-019-00485-yJoshi, M., Cetroni, B., Camacho, A., Krueger, C., & Midey, A. J. (2014). Analysis of synthetic cathinones and associated psychoactive substances by ion mobility spectrometry. Forensic Science International, 244, 196-206. doi:10.1016/j.forsciint.2014.08.033Peters, J. R., Keasling, R., Brown, S. D., & Pond, B. B. (2016). Quantification of Synthetic Cathinones in Rat Brain Using HILIC–ESI-MS/MS. Journal of Analytical Toxicology. doi:10.1093/jat/bkw074Williams, M., Martin, J., & Galettis, P. (2017). A Validated Method for the Detection of 32 Bath Salts in Oral Fluid. Journal of Analytical Toxicology, 41(8), 659-669. doi:10.1093/jat/bkx055Diestelmann, M., Zangl, A., Herrle, I., Koch, E., Graw, M., & Paul, L. D. (2018). MDPV in forensic routine cases: Psychotic and aggressive behavior in relation to plasma concentrations. Forensic Science International, 283, 72-84. doi:10.1016/j.forsciint.2017.12.003Garrido, E., Pla, L., Lozano-Torres, B., El Sayed, S., Martínez-Máñez, R., & Sancenón, F. (2018). Chromogenic and Fluorogenic Probes for the Detection of Illicit Drugs. ChemistryOpen, 7(5), 401-428. doi:10.1002/open.201800034García‐Fernández, A., Aznar, E., Martínez‐Máñez, R., & Sancenón, F. (2019). New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers. Small, 16(3), 1902242. doi:10.1002/smll.201902242Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jGiménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Towards Chemical Communication between Gated Nanoparticles. Angewandte Chemie International Edition, n/a-n/a. doi:10.1002/anie.201405580Luis, B., Llopis‐Lorente, A., Rincón, P., Gadea, J., Sancenón, F., Aznar, E., … Martínez‐Máñez, R. (2019). An Interactive Model of Communication between Abiotic Nanodevices and Microorganisms. Angewandte Chemie International Edition, 58(42), 14986-14990. doi:10.1002/anie.201908867Garrido, E., Alfonso, M., Díaz de Greñu, B., Lozano‐Torres, B., Parra, M., Gaviña, P., … Sancenón, F. (2020). Nanosensor for Sensitive Detection of the New Psychedelic Drug 25I‐NBOMe. Chemistry – A European Journal, 26(13), 2813-2816. doi:10.1002/chem.201905688Ribes, À., Aznar, E., Santiago-Felipe, S., Xifre-Perez, E., Tormo-Mas, M. Á., Pemán, J., … Martínez-Máñez, R. (2019). Selective and Sensitive Probe Based in Oligonucleotide-Capped Nanoporous Alumina for the Rapid Screening of Infection Produced by Candida albicans. ACS Sensors, 4(5), 1291-1298. doi:10.1021/acssensors.9b00169Oroval, M., Coll, C., Bernardos, A., Marcos, M. D., Martínez-Máñez, R., Shchukin, D. G., & Sancenón, F. (2017). Selective Fluorogenic Sensing of As(III) Using Aptamer-Capped Nanomaterials. ACS Applied Materials & Interfaces, 9(13), 11332-11336. doi:10.1021/acsami.6b15164Aznar, E., Villalonga, R., Giménez, C., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications, 49(57), 6391. doi:10.1039/c3cc42210kGiménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Towards Chemical Communication between Gated Nanoparticles. Angewandte Chemie International Edition, n/a-n/a. doi:10.1002/anie.201405580Maerten, C., Garnier, T., Lupattelli, P., Chau, N. T. T., Schaaf, P., Jierry, L., & Boulmedais, F. (2015). Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry. Langmuir, 31(49), 13385-13393. doi:10.1021/acs.langmuir.5b03774Beck, J. S., Vartuli, J. C., Roth, W. J., Leonowicz, M. E., Kresge, C. T., Schmitt, K. D., … Schlenker, J. L. (1992). A new family of mesoporous molecular sieves prepared with liquid crystal templates. Journal of the American Chemical Society, 114(27), 10834-10843. doi:10.1021/ja00053a020Cai, Q., Luo, Z.-S., Pang, W.-Q., Fan, Y.-W., Chen, X.-H., & Cui, F.-Z. (2001). Dilute Solution Routes to Various Controllable Morphologies of MCM-41 Silica with a Basic Medium. Chemistry of Materials, 13(2), 258-263. doi:10.1021/cm990661zDebruyne, D., Loilier, M., Cesbron, A., Le Boisselier, R., & Bourgine, J. (2014). Emerging drugs of abuse: current perspectives on substituted cathinones. Substance Abuse and Rehabilitation, 37. doi:10.2147/sar.s37257Marusich, J. A., Antonazzo, K. R., Wiley, J. L., Blough, B. E., Partilla, J. S., & Baumann, M. H. (2014). Pharmacology of novel synthetic stimulants structurally related to the «bath salts» constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology, 87, 206-213. doi:10.1016/j.neuropharm.2014.02.016Baumann, M. H., Partilla, J. S., Lehner, K. R., Thorndike, E. B., Hoffman, A. F., Holy, M., … Schindler, C. W. (2012). Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products. Neuropsychopharmacology, 38(4), 552-562. doi:10.1038/npp.2012.20

Fecal microbiota composition is related to brown adipose tissue 18F‑fluorodeoxyglucose uptake in young adults

Objective Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults. Methods 82 young adults (58 women, 21.8 ± 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. 18F-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles. Results The relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho ≤ − 0.232, P ≤ 0.027), whereas the relative abundance of Bifidobacterium genus was positively correlated with BAT SUVmean and BAT SUVpeak (all rho ≥ 0.262, P ≤ 0.012). On the other hand, the relative abundance of Sutterellaceae and Bifidobacteriaceae families was positively correlated with 18FFDG uptake by WAT and skeletal muscles (all rho ≥ 0.213, P ≤ 0.042). All the analyses were adjusted for the PET/CT scan date as a proxy of seasonality. Conclusion Our results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings.Universidad de Granada / CBUASpanish Ministry of Economy and Competitiveness via Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393 PTA 12264-IRetos de la Sociedad DEP2016-79512-REuropean Commission Spanish Government FPU13/04365 FPU16/05159 FPU17/01523Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas De Investigacion Cooperativa RETIC Red SAMID RD16/0022InFLAMES Flagship Programme of the Academy of Finland 337530NextGenerationEU RR_C_2021_04AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGREuropean Commission through the "European funds for regional development" (EFRE)regional Ministry of Economy, Science and Digitalization of Saxony-Anhalt as part of the "Autonomy in old Age"(AiA) research group for "LiLife" Project ZS/2018/11/95324MIRACUMFederal Ministry of Education & Research (BMBF) FKZ 01ZZ1801HFundacion Alfonso Martin Escuder

A larger brown fat volume and lower radiodensity are related to a greater cardiometabolic risk, especially in young men

Objectives: Brown adipose tissue (BAT) is important in the maintenance of cardiometabolic health in rodents. Recent reports appear to suggest the same in humans, although if this is true remains elusive partly because of the methodological bias that affected previous research. This cross-sectional work reports the relationships of cold-induced BAT volume, activity (peak standardized uptake, SUVpeak), and mean radiodensity (an inverse proxy of the triacylglycerols content) with the cardiometabolic and inflammatory profile of 131 young adults, and how these relationships are influenced by sex and body weight.Design: This is a cross-sectional study.Methods: Subjects underwent personalized cold exposure for 2 h to activate BAT, followed by static F-18-fluorodeoxyglucose PET-CT scanning to determine BAT variables. Information on cardiometabolic risk (CMR) and inflammatory markers was gathered, and a CMR score and fatty liver index (FLI) were calculated.Results: In men, BAT volume was positively related to homocysteine and liver damage markers concentrations (independently of BMI and seasonality) and the FLI (all P 0.05).Conclusions: A larger BAT volume and a lower BAT mean radiodensity are related to a higher CMR, especially in young men, which may support that BAT acts as a compensatory organ in states of metabolic disruption.</p

Sensitive detection of SARS-CoV-2 seroconversion by flow cytometry reveals the presence of nucleoprotein-reactive antibodies in unexposed individuals

There is an ongoing need of developing sensitive and specific methods for the determination of SARS-CoV-2 seroconversion. For this purpose, we have developed a multiplexed flow cytometric bead array (C19BA) that allows the identification of IgG and IgM antibodies against three immunogenic proteins simultaneously: the spike receptor-binding domain (RBD), the spike protein subunit 1 (S1) and the nucleoprotein (N). Using different cohorts of samples collected before and after the pandemic, we show that this assay is more sensitive than ELISAs performed in our laboratory. The combination of three viral antigens allows for the interrogation of full seroconversion. Importantly, we have detected N-reactive antibodies in COVID-19-negative individuals. Here we present an immunoassay that can be easily implemented and has superior potential to detect low antibody titers compared to current gold standard serology methods.Acknowledgements: We thank Petros Tyrakis and Iván Martínez-Forero for critical reading and editing of the manuscript. Support was provided by the Severo Ochoa Excellence Accreditation from MCIU (SEV-2016-0644) and the SPRI I+D COVID-19 fund (Gobierno Vasco). Personal fellowships: A.A.-V. (La Caixa Inphinit LCF/BQ/DR20/11790022), A.B. (AECC Bizkaia), A.G.d.R (Bikaintek), A.P. (Ramón y Cajal), B.J.-L. (Gob. Vasco), and E.P.-F. (Juan de la Cierva-Formación). M.L.M.-C. acknowledges RTC2019-007125-1, DTS20/00138, SAF2017-87301-R, and BBVA UMBRELLA project. M.L.-H. acknowledges the ISCIII for grant COV20-0170 and the Government of Cantabria for grant 2020UIC22-PUB-0019. O.M., J.-M.M., and N.G.A.A. acknowledge the Agencia Estatal de Investigación (Spain) for grants CTQ2015-68756-R, RTI2018-101269-BI00, and RTI2018-095700-B-I00, respectively. A.P. has received grant funding from the European Research Council (ERC), grant agreement number 804236 (Horizon 2020), and the FERO Foundation

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial

Exercise modulates both brown adipose tissue (BAT)metabolismand white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n=31, and VIG-EX; n=31).We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6ml; Δ MOD-EX: −15.5 ± 62.1ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.Spanish Government PI13/01393Retos de la Sociedad DEP2016-79512-R PTA-12264IEuropean CommissionSpanish Government FPU13/04365 FPU14/04172 FPU15/04059 FPU16/03653 FPU19/01609Consejo Nacional de Ciencia y Tecnologia (CONACyT) 440575Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Plan Propio de Investigacion 2018 -Programa Contratos-PuentePrograma Perfecionamiento de DoctoresJunta de Andalucia Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGRJunta de Andalucia P18-RT-4455Fundacion Alfonso Martin EscuderoMaria Zambrano fellowship by the Ministerio de Universidades y la Union Europea-NextGenerationEU RR_C_2021_04Novo Nordisk FoundationNovocure Limited NNF18OC003239

Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures

Objective: despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). Design: a prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. Results: an initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. Conclusion: implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.Funding: we thank the financial support of CIBERehd; grants PI16/01126 and PI19/00163 from Instituto de Salud Carlos III (ISCIII) cofinanced by ’Fondo Europeo de Desarrollo Regional’ (FEDER) ’Una manera de hacer Europa’; grants 58/2017 and 55/2018 from Gobierno de Navarra Salud; grant 0011-1411-2020-000010 from AGATA Strategic Project from Gobierno de Navarra; grant 2020/101 from Euroregion Nouvelle Aquitaine-Euskadi-Navarra; Fundación Eugenio Rodríguez Pascual; Fundación Mario Losantos, Fundación M Torres; grant 2018/117 from AMMF, the Cholangiocarcinoma Charity; the COST Action CA181122 Euro-cholangio-Net; POSTD18014AREC postdoctoral fellowship from AECC to MA; and Ramón y Cajal Program contracts RYC-2014-15242 and RYC-2018-024475-1 to FJC and MGFB

Q-SAPS?: què saben sobre salut pública a l’atenció primària?

Malalties; Declaració obligatòria; Brots epidèmicsEnfermedades; Declaración obligatoria; Brotes epidémicosDiseases; Mandatory declaration; Epidemic outbreaksEl treball d’aquesta comunitat de pràctica (CoP) pretén ajudar a detectar mancances de coneixement sobre la salut pública entre els professionals de l’atenció primària i elaborar un document de propostes per millorar el coneixement referit en aquest àmbit. Amb les següents propostes de valor: 1-Conèixer les funcions de cada actor en les malalties de declaració obligatòria (MDO), emergents i brots epidèmics. 2-Detectar mancances de coneixement i dificultats per a declarar. 3-Saber la utilitat de declarar MDO i brots epidèmics, ja que no és només un simple registre sinó que hi ha una actuació al darrere. 4-Conèixer les actuacions comunitàries que cal fer en cada malaltia per controlar-la, i brots epidèmics.El trabajo de esta comunidad de práctica (CoP) pretende ayudar a detectar carencias de conocimiento sobre la salud pública entre los profesionales de la atención primaria y elaborar un documento de propuestas para mejorar el conocimiento referido en este ámbito. Con las siguientes propuestas de valor: 1-Conocer las funciones de cada actor en las enfermedades de declaración obligatoria (MDO), emergentes y brotes epidémicos. 2-Detectar carencias de conocimiento y dificultades para declarar. 3-Saber la utilidad de declarar EDO y brotes epidémicos, ya que no es sólo un simple registro sino que hay una actuación detrás. 4-Conocer las actuaciones comunitarias a realizar en cada enfermedad para controlarla, y brotes epidémicos.The work of this community of practice (CoP) aims to help detect gaps in knowledge about public health among primary care professionals and prepare a document of proposals to improve the knowledge referred to in this area. With the following value propositions: 1-Know the functions of each actor in notifiable diseases, emerging diseases and epidemic outbreaks. 2-Detect knowledge gaps and difficulties in declaring. 3-Know the usefulness of declaring notifiable diseases and epidemic outbreaks, since it is not just a simple record but there is an action behind it. 4-Know the community actions to be carried out in each disease to control it, and epidemic outbreaks