SARS-CoV-2 Infection Among Healthcare Workers in Tijuana, Mexico: A Cross-Sectional Study

Background: Healthcare workers (HCW) are a high-risk group for contraction of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this study was to estimate the effect size of being a HCW and acquiring coronavirus disease 2019 (COVID-19) at the Mexican Institute of Social Security (IMSS) in Tijuana, Mexico. Methods: A cross-sectional study of the Epidemiologic Surveillance Online Notification System database was conducted, including entries from Tijuana City between March 11, 2020 to May 1, 2020. Multiple imputation was performed for SARS-CoV-2 RT-PCR result where data was missing. Prevalence odds ratios (POR) were calculated to estimate the effect size of HCWs contracting COVID-19 compared to the general population (GP). Results: From a total of 10,216 entries, 6,256 patients were included for analysis. HCW status was significantly associated with higher odds of acquiring COVID-19, (POR=1.730, 95% Confidence Interval [95%CI]=1.459;2.050). Nurses had double odds (POR=2.339, 95%CI=1.804;3.032) than the GP. Physicians had a POR=1.828 (95%CI=0.766;1.380). Resident physician status was double the likelihood of the GP (POR=2.166, 95%CI=0.933;5.025). Meanwhile, being an intern had a protective factor (POR=0.253, 95%CI=0.085;0.758). Among medical specialties, emergency medicine had the highest exposure-effect association, followed by anesthesiologists. Conclusion: HCW had up to 73% increased odds of acquiring COVID-19 than the GP in Tijuana, Mexico. Nurses were the group with the highest likelihood out of all HCW, as a result of prolonged and close contact with patients. Emergency medicine and anesthesiology were the medical specialties with the highest odds of infection because they frequently perform aerosol-generating procedures

Application of laser backscattering imaging for the physico-chemical characterisation of antimicrobial silica particles functionalised with plant essential oils

[EN] The capacity of orthogonal imaging applied to laser-backscattering for characterising antimicrobial particles based on immobilised essential oils was tested. Different particles were synthesised using various particle and oils. Samples were characterised physico-chemically and by an imaging technique. The technique recorded the generated patterns because of the laser-particles interaction during the sedimentation process. The series of images were transformed into an orthogonal image. Data extraction varied depending on the fragmentation degree of image length. After the multivariate analysis, the physico-chemical results showed variability due to particle size. That variability diminished the effect of oils for large sizes. The imaging data collected these properties, which could be used to recognise both particle size and oil type. Thus the prediction of the properties was successful. The position in the physico-chemical space of variance was also predicted. Hence this technique could complement a low-cost method to evaluate the properties of functionalised particles with oils.The authors gratefully acknowledge the financial support from the University Polytechnic of Valencia for Programme "Ayudas para la Contratacion de Doctores para el Acceso al Sistema Espanol de Ciencia, Tecnologia e Innovacion, en Estructuras de Investigacion de la UPV (PAID-10-17)", "Generalitat Valenciana" for their postdoctoral fellowship (APOSTD/2019/118) and the Ministerio de Ciencia, Innovacion y Universidades, the Agencia Estatal de Investigacion and FEDER-EU (Project RTI2018-101599-B-C21).Verdú, S.; Ruiz Rico, M.; Pérez Jiménez, AJ.; Barat Baviera, JM.; Grau Meló, R. (2020). Application of laser backscattering imaging for the physico-chemical characterisation of antimicrobial silica particles functionalised with plant essential oils. Journal of Food Engineering. 280:1-10. https://doi.org/10.1016/j.jfoodeng.2020.109990S110280Bell, N. C., Minelli, C., Tompkins, J., Stevens, M. M., & Shard, A. G. (2012). Emerging Techniques for Submicrometer Particle Sizing Applied to Stöber Silica. Langmuir, 28(29), 10860-10872. doi:10.1021/la301351kChen, F., Shi, Z., Neoh, K. G., & Kang, E. T. (2009). Antioxidant and antibacterial activities of eugenol and carvacrol-grafted chitosan nanoparticles. Biotechnology and Bioengineering, 104(1), 30-39. doi:10.1002/bit.22363Dickinson, E. (2012). Use of nanoparticles and microparticles in the formation and stabilization of food emulsions. Trends in Food Science & Technology, 24(1), 4-12. doi:10.1016/j.tifs.2011.09.006Emmerich, J., Tang, Q., Wang, Y., Neubauer, P., Junne, S., & Maaß, S. (2019). Optical inline analysis and monitoring of particle size and shape distributions for multiple applications: Scientific and industrial relevance. Chinese Journal of Chemical Engineering, 27(2), 257-277. doi:10.1016/j.cjche.2018.11.011García-Ríos, E., Ruiz-Rico, M., Guillamón, J. M., Pérez-Esteve, É., & Barat, J. M. (2018). Improved antimicrobial activity of immobilised essential oil components against representative spoilage wine microorganisms. Food Control, 94, 177-186. doi:10.1016/j.foodcont.2018.07.005Pisoschi, A. M., Pop, A., Georgescu, C., Turcuş, V., Olah, N. K., & Mathe, E. (2018). An overview of natural antimicrobials role in food. European Journal of Medicinal Chemistry, 143, 922-935. doi:10.1016/j.ejmech.2017.11.095Ribes, S., Ruiz-Rico, M., Pérez-Esteve, É., Fuentes, A., & Barat, J. M. (2019). Enhancing the antimicrobial activity of eugenol, carvacrol and vanillin immobilised on silica supports against Escherichia coli or Zygosaccharomyces rouxii in fruit juices by their binary combinations. LWT, 113, 108326. doi:10.1016/j.lwt.2019.108326Ribes, S., Ruiz-Rico, M., Pérez-Esteve, É., Fuentes, A., Talens, P., Martínez-Máñez, R., & Barat, J. M. (2017). Eugenol and thymol immobilised on mesoporous silica-based material as an innovative antifungal system: Application in strawberry jam. Food Control, 81, 181-188. doi:10.1016/j.foodcont.2017.06.006Ruiz-Rico, M., Pérez-Esteve, É., Bernardos, A., Sancenón, F., Martínez-Máñez, R., Marcos, M. D., & Barat, J. M. (2017). Enhanced antimicrobial activity of essential oil components immobilized on silica particles. Food Chemistry, 233, 228-236. doi:10.1016/j.foodchem.2017.04.118Śliwa, T., Jarzębski, M., & Szutkowski, K. (2015). Nanoparticle Tracking Analysis of Latex Standardized Beads. Current Topics in Biophysics, 37(1), 49-53. doi:10.2478/ctb-2014-0074Verdú, S., Barat, J. M., & Grau, R. (2019). Laser backscattering imaging as a non-destructive quality control technique for solid food matrices: Modelling the fibre enrichment effects on the physico-chemical and sensory properties of biscuits. Food Control, 100, 278-286. doi:10.1016/j.foodcont.2019.02.004Verdú, S., Barat, J. M., & Grau, R. (2019). Non destructive monitoring of the yoghurt fermentation phase by an image analysis of laser-diffraction patterns: Characterization of cow’s, goat’s and sheep’s milk. Food Chemistry, 274, 46-54. doi:10.1016/j.foodchem.2018.08.091Wang, W., Wen, Y., Lu, J. Q., Zhao, L., Al-Qaysi, S. A., & Hu, X.-H. (2019). Rapid classification of micron-sized particles of sphere, cylinders and ellipsoids by diffraction image parameters combined with scattered light intensity. Journal of Quantitative Spectroscopy and Radiative Transfer, 224, 453-459. doi:10.1016/j.jqsrt.2018.12.01

Hypertension Awareness, Treatment, and Control in Mexico: An Opportunistic Medical Student-led Blood Pressure Screening Campaign – A Cross-Sectional Study

Background: Hypertension is still a growing public health problem in Mexico. An estimated 151% increase in the number of individuals with hypertension is expected for 2050 if actions are not taken in the country. The aim of this study is to describe hypertension awareness, treatment, control and its associated factors in participants of an opportunistic medical student-led blood pressure screening campaign in Mexico. Methods: A cross-sectional study, using convenience sampling was performed, including participants aged 18 years and older from 15 Mexican states. Each participant completed a questionnaire about risk factors and had three BP measurements taken. Hypertension was defined as ?140/90 mmHg. Multiple imputation with linear regression was performed where data was missing. Results: From a population of 2 545 participants, 623 (24.5%) participants had hypertension. Of those with hypertension, 81.9% had a previous diagnosis of hypertension and only 16.1% were not on medication at the time of screening; 61% were controlled, 121% were uncontrolled patients and 18% were not aware they had hypertension. High marginalization was found to have the biggest proportion of uncontrolled cases (33%), while the number of unaware hypertensives in very low marginalization states doubled the national figure. More than half the participants taking antihypertensive agents were on a single medication, achieving control in almost 8 in 10 patients. Conclusion: It is important to continue making and supporting awareness raising campaigns in different settings across the country to generate more evidence and lead to better programs for improving hypertension detection in Mexico

Toxicological implications of amplifying the antibacterial activity of gallic acid by immobilisation on silica particles: a study on C. elegans

[EN] Immobilisation of natural compounds on solid supports to amplify antimicrobial properties has reported successful results, but modifications to physico-chemical properties can also imply modifications from a toxicological viewpoint. This work aimed to study the immobilising process of gallic acid in the antibacterial activity of L. innocua and its toxicological properties in vivo using Caenorhabditis elegans. The experiment was based on obtaining the minimum bactericidal concentration for free and immobilised gallic acid by comparing lethality, locomotion behaviour, chemotaxis and thermal stress resistance on C.elegans at those concentrations. The results showed a lowering minimum bactericidal concentration and modifications to nematode responses. Increased lethality and velocity of movements was observed. Immobilisation increased the repellent effect of gallic acid with a negative chemotaxis index. Thermal stress resistance was also affected, with higher mortality for immobilised gallic acid compared to bare particles and free gallic acid. Thus despite evidencing a generalised increase in the toxicity of gallic acid in vivo, lowering the minimum bactericidal concentration allowed a bacterial reduction of 99 % with less than one third of mortality for the nematodes exposed to free gallic acid.The authors gratefully acknowledge financial support from the University Polytechnic of Valencia by programme "Ayudas para la Contratacion de Doctores para el Acceso al Sistema Espanol de Ciencia, Tecnologia e Innovacion, en Estructuras de Investigacion de la UPV (PAID-10-17)" and the Ministerio de Ciencia, Innovacion y Universidades, the Agencia Estatal de Investigacion and FEDER-EU (Project RTI2018-101599-B-C21).Verdú, S.; Ruiz Rico, M.; Pérez Jiménez, AJ.; Barat Baviera, JM.; Talens Oliag, P.; Grau Meló, R. (2020). Toxicological implications of amplifying the antibacterial activity of gallic acid by immobilisation on silica particles: a study on C. elegans. Environmental Toxicology and Pharmacology. 80:1-8. https://doi.org/10.1016/j.etap.2020.103492S1880Abdel-Wahhab, M. A., Aljawish, A., Kenawy, A. M., El-Nekeety, A. A., Hamed, H. S., & Abdel-Aziem, S. H. (2016). Grafting of gallic acid onto chitosan nano particles enhances antioxidant activities in vitro and protects against ochratoxin A toxicity in catfish ( Clarias gariepinus ). Environmental Toxicology and Pharmacology, 41, 279-288. doi:10.1016/j.etap.2015.12.005Borges, A., Saavedra, M. J., & Simões, M. (2012). The activity of ferulic and gallic acids in biofilm prevention and control of pathogenic bacteria. Biofouling, 28(7), 755-767. doi:10.1080/08927014.2012.706751Borges, A., Ferreira, C., Saavedra, M. J., & Simões, M. (2013). Antibacterial Activity and Mode of Action of Ferulic and Gallic Acids Against Pathogenic Bacteria. Microbial Drug Resistance, 19(4), 256-265. doi:10.1089/mdr.2012.0244Brenner, S. (1974). THE GENETICS OF CAENORHABDITIS ELEGANS. Genetics, 77(1), 71-94. doi:10.1093/genetics/77.1.71Jayaraman, P., Sakharkar, M. K., Lim, C. S., Tang, T. H., & Sakharkar, K. R. (2010). Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro. International Journal of Biological Sciences, 556-568. doi:10.7150/ijbs.6.556Li, L., & Wang, H. (2013). Antibacterial Agents: Enzyme-Coated Mesoporous Silica Nanoparticles as Efficient Antibacterial Agents In Vivo (Adv. Healthcare Mater. 10/2013). Advanced Healthcare Materials, 2(10), 1298-1298. doi:10.1002/adhm.201370050Margie, O., Palmer, C., & Chin-Sang, I. (2013). C. elegans Chemotaxis Assay. Journal of Visualized Experiments, (74). doi:10.3791/50069Pędziwiatr-Werbicka, E., Miłowska, K., Podlas, M., Marcinkowska, M., Ferenc, M., Brahmi, Y., … El Kadib, A. (2014). Oleochemical-Tethered SBA-15-Type Silicates with Tunable Nanoscopic Order, Carboxylic Surface, and Hydrophobic Framework: Cellular Toxicity, Hemolysis, and Antibacterial Activity. Chemistry - A European Journal, 20(31), 9596-9606. doi:10.1002/chem.201402583Pisoschi, A. M., Pop, A., Georgescu, C., Turcuş, V., Olah, N. K., & Mathe, E. (2018). An overview of natural antimicrobials role in food. European Journal of Medicinal Chemistry, 143, 922-935. doi:10.1016/j.ejmech.2017.11.095Qi, G., Li, L., Yu, F., & Wang, H. (2013). Vancomycin-Modified Mesoporous Silica Nanoparticles for Selective Recognition and Killing of Pathogenic Gram-Positive Bacteria Over Macrophage-Like Cells. ACS Applied Materials & Interfaces, 5(21), 10874-10881. doi:10.1021/am403940dRuiz-Rico, M., Daubenschüz, H., Pérez-Esteve, É., Marcos, M. D., Amorós, P., Martínez-Máñez, R., & Barat, J. M. (2016). Protective effect of mesoporous silica particles on encapsulated folates. European Journal of Pharmaceutics and Biopharmaceutics, 105, 9-17. doi:10.1016/j.ejpb.2016.05.016Ruiz-Rico, M., Pérez-Esteve, É., Bernardos, A., Sancenón, F., Martínez-Máñez, R., Marcos, M. D., & Barat, J. M. (2017). Enhanced antimicrobial activity of essential oil components immobilized on silica particles. Food Chemistry, 233, 228-236. doi:10.1016/j.foodchem.2017.04.118Saul, N., Pietsch, K., Stürzenbaum, S. R., Menzel, R., & Steinberg, C. E. W. (2011). Diversity of Polyphenol Action in Caenorhabditis elegans: Between Toxicity and Longevity. Journal of Natural Products, 74(8), 1713-1720. doi:10.1021/np200011aSingulani, J. de L., Scorzoni, L., Gomes, P. C., Nazaré, A. C., Polaquini, C. R., Regasini, L. O., … Mendes-Giannini, M. J. S. (2017). Activity of gallic acid and its ester derivatives in Caenorhabditis elegans and zebrafish (Danio rerio) models. Future Medicinal Chemistry, 9(16), 1863-1872. doi:10.4155/fmc-2017-0096Soobrattee, M. A., Neergheen, V. S., Luximon-Ramma, A., Aruoma, O. I., & Bahorun, T. (2005). Phenolics as potential antioxidant therapeutic agents: Mechanism and actions. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 579(1-2), 200-213. doi:10.1016/j.mrfmmm.2005.03.023Techer, D., Milla, S., Fontaine, P., Viot, S., & Thomas, M. (2015). Acute toxicity and sublethal effects of gallic and pelargonic acids on the zebrafish Danio rerio. Environmental Science and Pollution Research, 22(7), 5020-5029. doi:10.1007/s11356-015-4098-2Vico, T. A., Arce, V. B., Fangio, M. F., Gende, L. B., Bertran, C. A., Mártire, D. O., & Churio, M. S. (2016). Two choices for the functionalization of silica nanoparticles with gallic acid: characterization of the nanomaterials and their antimicrobial activity against Paenibacillus larvae. Journal of Nanoparticle Research, 18(11). doi:10.1007/s11051-016-3652-2Wilson, M. A., Shukitt-Hale, B., Kalt, W., Ingram, D. K., Joseph, J. A., & Wolkow, C. A. (2006). Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell, 5(1), 59-68. doi:10.1111/j.1474-9726.2006.00192.xYuan, P., Pan, L., Xiong, L., Tong, J., Li, J., Huang, J., … Liu, Z. (2018). Black tea increases hypertonic stress resistance in C. elegans. Food & Function, 9(7), 3798-3806. doi:10.1039/c7fo02017aZevian, S. C., & Yanowitz, J. L. (2014). Methodological considerations for heat shock of the nematode Caenorhabditis elegans. Methods, 68(3), 450-457. doi:10.1016/j.ymeth.2014.04.015Zhou, D., Yang, J., Li, H., Cui, C., Yu, Y., Liu, Y., & Lin, K. (2016). The chronic toxicity of bisphenol A to Caenorhabditis elegans after long-term exposure at environmentally relevant concentrations. Chemosphere, 154, 546-551. doi:10.1016/j.chemosphere.2016.04.01

Patología de los tumores neuroblásticos: evaluación pronóstica. Experiencia del centro español de referencia de la SEOP para estudios biopatológicos del neuroblastoma (1992-2005)

Antecedentes: Los tumores neuroblásticos son los tumores sólidos extracraneales más frecuentes en la infancia y se caracterizan por una evolución clínica heterogénea que va desde una progresión rápida a una regresión tumoral espontánea. Existen factores pronósticos conocidos que determinan dicha evolución como son la edad, estadiaje, histopatología, estatus de MYCN, ploidía y diversas ganancias y pérdidas cromosómicas. El objetivo del trabajo es describir nuestra experiencia como laboratorio de referencia español para la determinación de estos parámetros pronósticos. Métodos: Material tumoral de pacientes con neuroblastoma, remitido a nuestro laboratorio desde 1992 hasta 2005, ha sido sometido a estudio histopatológico, molecular para determinar la amplificación de MYCN, histoquímico y morfométrico para estudiar la ploidía y se ha introducido la técnica de CGH para el análisis de ganancias y perdidas cromosómicas. Resultados: El seguimiento clínico durante estos años, ha demostrado la importancia pronóstica de la clasificación histológica Internacional Neuroblastoma Pathology Classification (INPC), la relación de un contenido diploide-tetraploide de ADN con el histopronóstico desfavorable, la proporción del 20% de casos con amplificación de MYCN y su carácter pronostico desfavorable, así como la presencia de ganancias y pérdidas cromosómicas como 11q- que confieren mal pronóstico. Conclusiones: Se confirma la necesidad de determinar parámetros morfológicos y genéticos de valor pronóstico con el fin de estratificar la terapéutica apropiada de elección en los pacientes con neuroblastoma.Background: Neuroblastic tumors are the most frequent extracranial solid tumors in childhood, and are characterized by a heterogeneous clinic behavior, ranging from a rapid progression of disease to a spontaneous regression. Prognostic indicators that condition such behavior, such as age, staging, histopathology, MYCN oncogene status, ploidy, and diverse chromosomal losses and gains, have been demonstrated. The aim of present work is to describe our experience as reference laboratory for the determination of these prognostic factors in neuroblastic tumors. Methods: Tumor material from patients with neuroblastoma, submitted to our laboratory from 1992 to 2005 has been analyzed. Histopathology following Internacional Neuroblastoma Pathology Classification (INPC) classification, PCR and FISH for MYCN status, static cytometry for ploidy and CGH for chromosomal gains and losses, were performed. Results: The clinical follow-up has demonstrated the prognostic value of INPC, the relationship between diploid-tetraploid DNA content and unfavorable histology, the existence of 20% MYCN amplified cases showing an unfavorable prognosis as well as the presence of chromosomal gains and losses especially 11q-, that confer unfavorable prognosis. Conclusions: We confirm the importance of determining morphological and genetic prognostic parameters in neuroblastic tumors in order to stratify the patients to receive the correct therapy accordingly.Navarro Fos, Samuel, [email protected] ; Llombart Bosch, Antonio, [email protected] ; Pellin Perez, Antonio, [email protected] ; Burgues Gasion, Octavio, [email protected]; Ruiz Sauri, Amparo, [email protected]; Piqueras Franco, Marta, [email protected] ; Noguera Salva, Rosa, [email protected]

Metal−Organic Frameworks Based on a Janus-Head Biquinoline Ligand as Catalysts in the Transformation of Carbonyl Compounds into Cyanohydrins and Alcohols

A new family of metal−organic frameworks (MOFs) named GR-MOFs with the chemical formula {[Mx(BCA)y]- (H2O)z(DMF)w} (x,y,z,w: 1,1,2,0; 1,1.5,0,1; 1,2,2,1; and 1,1,0,2 for GR-MOF-11 to 14, respectively) based on s-block [M: Sr (GRMOF- 11), Ba (GR-MOF-14)] and d-block [M: Y (GR-MOF-12) and Cd (GR-MOF-13)] metals together with the biquinoline ligand 2,2′-bicinchoninic acid (H2BCA) has been synthetized by a solvothermal route and fully characterized by elemental and thermogravimetric analysis, Fourier transform infrared spectroscopy, photoluminescence, particle size distribution through optical microscopy, electrophoretic mobility, and finally, X-ray singlecrystal and powder diffraction. The structural characterization reveals that these 2D and 3D MOFs possess a rich variety of coordination modes that maintained the Janus-head topology on the ligand in most of the cases. The new MOFs were studied in the catalyzed cyanosilylation and hydroboration of an extensive group of aldehydes and ketones, wherein the s-block metal-based MOFs GR-MOF-11 and GR-MOF-14 provided the highest efficiency ever reported in the MOF-catalyzed cyanosilylation of carbonyl compounds by using only 0.5 mol % of catalyst loading, room temperature, and solvent-free conditions. Furthermore, the hydroboration of ketones has been reported for the first time with this type of s-block metal catalysts obtaining from moderate to good conversions.MCIN/AEI CTQ2017-84334 R PGC2018-102052 B-C21 PGC2018-102052 A-C22ERDF A way of making EuropeJunta de Andalucia 102C2000004 CV20-78799 P20_01041UAL-FEDER UAL2020-AGR-B1781FEDER 2014-2020 A-RNM-433-UGR18ProyExcel_00386 ProyExcel_00105B-FQM-734-UGR20 FQM-376 FQM-394Basque Government IT1755-22 IT1500-22Gobierno de Espana MCIN/AEI PDC2021-121248-I00 PLEC2021-007774Juan de la Cierva Incorporacion Fellowship IJC2019-038894-IHipatia fellowship (University of Almeria)Universidad de Granada/CBU

The relationship between sociocultural factors and autobiographical memoriesfrom childhood: the role of formal schooling

Cross-cultural differences in autobiographical memory (AM) are associated with cultural variations. In models of the self and parental reminiscing style, but not many studies have analysed the relationship between AM and specific cultural practices such as formal schooling. Theoreticians like [Greenfield, P. M. (2009). Linking social change and developmental change: Shifting. pathways of human development. Developmental Psychology, 45, 401–418. doi:10.1037/a0014726; Kağitçibaşi, C. (2005). Autonomy and relatedness in cultural context. Implications for self and family. Journal of Cross-Cultural Psychology, 36, 403–422. doi:10.1177/0022022105275959] and [Keller, H. (2007). Children development across cultures. New York: Lawrence Erlbaum Associates] have considered formal schooling as an engine towards the model of independence; however, the empirical evidence in this regard is inconclusive: while some studies found evidence of a relation between formal schooling and characteristics of AM, others did not. To solve this inconsistency, the present study compared orally narrated childhood memories of Mexican adults with three different levels of education (from rudimentary literacy to university). Results support a relationship between formal schooling and AM in the predicted direction: More educated participants reported longer, more specific and more self-oriented memories than those with less schooling experience did. Some gender differences were also observed, with males generally reporting more individually and less socially oriented memories than females, except for university level participants. We conclude that these results support Greenfield’s theory about formal schooling as a sociocultural factor that promotes the cultural pathway to independence, as well as complexity and context-boundedness of gender differences in AM.Universidad Autónoma de TamaulipasPlan Estatal de Investigación Científica y Técnica y de Innovación (PEICTI

Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer’s disease.

Background: The complex pathophysiology of Alzheimer’s disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit. Methods: In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse− model. Results: We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3–CA1 synapse, both basal synaptic transmission and longterm potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron–glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH−/− animals. Conclusion: In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer’s disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the diseasepost-print4206 K

Overexpression of a SDD1-Like Gene From Wild Tomato Decreases Stomatal Density and Enhances Dehydration Avoidance in Arabidopsis and Cultivated Tomato

Stomata are microscopic valves formed by two guard cells flanking a pore, which are located on the epidermis of most aerial plant organs and are used for water and gas exchange between the plant and the atmosphere. The number, size and distribution of stomata are set during development in response to changing environmental conditions, allowing plants to minimize the impact of a stressful environment. In Arabidopsis, STOMATAL DENSITY AND DISTRIBUTION 1 (AtSDD1) negatively regulates stomatal density and optimizes transpiration and water use efficiency (WUE). Despite this, little is known about the function of AtSDD1 orthologs in crop species and their wild stress-tolerant relatives. In this study, SDD1-like from the stress-tolerant wild tomato Solanum chilense (SchSDD1-like) was identified through its close sequence relationship with SDD1-like from Solanum lycopersicum and AtSDD1. Both Solanum SDD1-like transcripts accumulated in high levels in young leaves, suggesting that they play a role in early leaf development. Arabidopsis sdd1-3 plants transformed with SchSDD1-like under a constitutive promoter showed a significant reduction in stomatal leaf density compared with untransformed sdd1-3 plants. Additionally, a leaf dehydration shock test demonstrated that the reduction in stomatal abundance of transgenic plants was sufficient to slow down dehydration. Overexpression of SchSDD1-like in cultivated tomato plants decreased the stomatal index and density of the cotyledons and leaves, and resulted in higher dehydration avoidance. Taken together, these results indicate that SchSDD1-like functions in a similar manner to AtSDD1 and suggest that Arabidopsis and tomatoes share this component of the stomatal development pathway that impinges on water status

Cannabinoid CB2 Receptors Modulate Microglia Function and Amyloid Dynamics in a Mouse Model of Alzheimer's Disease

The distribution and roles of the cannabinoid CB2 receptor in the CNS are still a matter of debate. Recent data suggest that, in addition to its presence in microglial cells, the CB2 receptor may be also expressed at low levels, yet biologically relevant, in other cell types such as neurons. It is accepted that the expression of CB2 receptors in the CNS is low under physiological conditions and is significantly elevated in chronic neuroinflammatory states associated with neurodegenerative diseases such as Alzheimer's disease. By using a novel mouse model (CB2EGFP/f/f), we studied the distribution of cannabinoid CB2 receptors in the 5xFAD mouse model of Alzheimer's disease (by generating 5xFAD/CB2EGFP/f/f mice) and explored the roles of CB2 receptors in microglial function. We used a novel selective and brain penetrant CB2 receptor agonist (RO6866945) as well as mice lacking the CB2 receptor (5xFAD/CB2-/-) for these studies. We found that CB2 receptors are expressed in dystrophic neurite-associated microglia and that their modulation modifies the number and activity of microglial cells as well as the metabolism of the insoluble form of the amyloid peptide. These results support microglial CB2 receptors as potential targets for the development of amyloid-modulating therapies.Funding The present work has been supported by a grant from Ministerio de Ciencia e Innovacion (ref PID2019-108992RB-I00 and ref PID2019-107548RB-I00) to JR and PG, respectively, by the Basque Government (ref IT1230-19) to PG, and the Research and Education Component of the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin to CJH