Modular total syntheses of thymifodioic/incanic acids

The first total synthesis of the bioactive natural product 2,6-(E,E)-thymifodioic acid, also called incanic acid, and its stereoisomers is described. An unified, iterative and modular strategy was envisioned, achieving the synthesis of the goals products after five reaction steps in an overall yield ranging from 8% to 16%. The key step is a non-expensive easy to perform Horner–Wadsworth–Emmons condensation.Fil: Álvarez Méndez, Sergio J.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-Orgánica "Antonio González"; EspañaFil: Saad, José Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Martín, Víctor S.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-Orgánica "Antonio González"; EspañaFil: García, Celina. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-Orgánica "Antonio González"; Españ

Anatomical dissection of the mimic facial musculature: iconographic review as a support to the complementary treatments in facial rejuvenation

A la hora de valorar las múltiples técnicas empleadas en el rejuvenecimiento facial y centrándonos de manera particular en aquellos procedimientos mínimamente invasivos complementarios a las intervenciones habituales en Cirugía Plástica-Estética, cobra especial relevancia el conocimiento exhaustivo de las estructuras musculares implicadas en la mímica facial. A tal efecto, se ha realizado un estudio anatómico en cadáveres frescos, en los que se han disecado las principales estructuras referidas. Se presenta un resumen iconográfico de los músculos faciales implicados, haciendo hincapié en su anatomía descriptiva y funcional, así como un recuerdo de las principales áreas problemáticas por alguna circunstancia especial (presencia de un nervio sensitivo o motor).To value the multiple technologies involved in facial rejuvenation and focusing in those minimally invasive complementary procedures to the usual Plastic and Aesthetic Surgeries, it´s very important the exhaustive knowledge of the muscular structures involved in the facial movements. To such an effect, an anatomical study has been realized in fresh corpses, dissecting the principal above-mentioned structures. We present an iconographic summary of the facial implied muscles, emphasizing in his descriptive and functional anatomy, as well as a recollection of the principal problematic areas for some special circumstance (presence of a sensory or motor nerv

Silk fibroin based magnetic nanocomposites for actuator applications

The need for technologies based environmentally friendlier materials, able to minimize the global dependence on fossil fuel derivatives, promotes the development of new hybrid materials based on natural polymers, such as silk derivatives. This work reports on a new generation of magnetically active materials based on silk fibroin (SF) from Bombyx mori silkworm. Magnetic cobalt ferrite (CFO) nanoparticles are introduced in an SF polymer matrix to develop CFO/SF nanocomposites with filler contents of up to 20 wt%. It is shown that the inclusion of CFO nanoparticles affects the β‐sheet conformation of SF polymer having relevant effect on mechanical and thermal properties. The incorporation of conductive nanoparticles into nonconductive matrix, induces an increase in electric conductivity and also in dielectric constant. The primitive magnetic behavior of CFO nanoparticles is successfully maintained after their incorporation into SF, which has made possible the processing of magnetic SF. These results enable the design and fabrication of a fully functional magnetic actuator based on SF, proving the suitable natural polymer‐based magnetic materials for a new generation of environmental‐friendlier smart and multifunctional materialsFundação para a Ciência e Tecnologia. Grant Numbers: UID/FIS/04650/2019, UID/EEA/04436/2019, UID/QUI/0686/2019, PTDC/FIS-MAC/28157/2017, PTDC/BTM-MAT/28237/2017, SFRH/BD/131729/2017, SFRH/BPD/112547/2015 Spanish Ministry of Economy and Competitiveness. Grant Number: MAT2016-76039- C4-3-R Basque Government Industry and Education Departments. Grant Number: PIBA- 2018-0

#8M Paro internacional de mujeres : Reflexiones en torno a la apropiación feminista de TIC

Tras un proceso intenso de organización y coordinación favorecido por tecnologías digitales, el 8 de marzo de 2017 se gestó un acontecimiento inédito en la historia feminista, el primer Paro Internacional de Mujeres con adhesión de 57 países, que contó con destacada participación en Latinoamérica. Este gesto político disruptivo suele ser invocado desde metáforas tales como: «marea feminista», «movimiento que hizo temblar la tierra» y «un tsunami de mujeres». La conmemoración del 8 de marzo como Día Internacional de las Mujeres cuenta con una vasta trayectoria en el activismo de organizaciones de mujeres y feministas del mundo, y adquirió renovado impulso a fines de los ’60 en el contexto de la segunda ola feminista de países del norte; mientras que en países latinoamericanos, en particular del cono sur, las acciones colectivas se retomaron en los años ’80, con la recuperación democrática. Desde entonces, de modo paulatino el 8 de marzo se instituyó como fecha clave del activismo de mujeres y feminista a nivel mundial, tanto como espacio de resistencia a la cooptación propiciada por el consumismo capitalista como ocasión para el agasajo de féminas.Facultad de Humanidades y Ciencias de la EducaciónInstituto de Investigaciones en Humanidades y Ciencias Sociale

Sensitivity and representativeness of One-Health surveillance for diseases of zoonotic potential at health facilities relative to household visits in rural Guatemala

Most human and animal disease notification systems are unintegrated and passive, resulting in underreporting. Active surveillance can complement passive efforts, but because they are resource-intensive, their attributes must be evaluated. We assessed the sensitivity and representativeness of One-Health surveillance conducted at health facilities compared to health facilities plus monthly household visits in three rural communities of Guatemala. From September 2017 to November 2018, we screened humans for acute diarrheal, febrile and respiratory infectious syndromes and canines, swine, equines and bovines for syndromic events or deaths. We estimated the relative sensitivity as the incidence rate ratio of detecting an event in health facility surveillance compared to household surveillance from Poisson models. We used interaction terms between the surveillance method and sociodemographic factors or time trends to assess effect modification as a measure of relative representativeness. We used generalized additive models with smoothing splines to model incidence over time by surveillance method. We randomized 216 households to health facility surveillance and 198 to health facility surveillance plus monthly household visits. Health facility surveillance alone was less sensitive than when combined with household surveillance by 0.42 (95% CI: 0.34, 0.53), 0.56 (95% CI: 0.39, 0.79), 0.02 (95% CI: 0.00, 0.10), 0.28 (95% CI: 0.15, 0.50) and 0.22 (95% CI: 0.03, 0.92) times for human acute infections, human severe acute infections, and deaths in canines, swine and equines, respectively. Health facility surveillance alone underrepresented Spanish speakers (interaction p-value = 0.0003) and persons in higher economic assets (interaction p-values = 0.0008). The trend in incidence over time was different between the two study groups, with a larger decrease in the group with household surveillance (all interaction p-values <0.10). Surveillance at health facilities under ascertains syndromes in humans and animals which leads to underestimation of the burden of zoonotic disease. The magnitude of under ascertainment was differentially by sociodemographic factors, yielding an unrepresentative sample of health events. However, it is less time-intensive, thus might be sustained over time longer than household surveillance. The choice between methodologies should be evaluated against surveillance goals and available resources

Stereoselective Synthesis of Highly Substituted Tetrahydropyrans through an Evans Aldol-Prins Strategy

A direct and general method for the synthesis of naturally occurring 2,3,4,5,6-pentasubstituted tetrahydropyrans has been developed, employing β,γ-unsaturated N-acyl oxazolidin-2-ones as key starting materials. The combination of the Evans aldol addition and the Prins cyclization allowed the diastereoselective and efficient generation of the desired oxacycles in two fashions: a one-pot Evans aldol-Prins protocol, in which five new σ bonds and five contiguous stereocenters were straightforwardly generated, and a two-step version, which additionally permitted the isolation of β,γ-unsaturated alcohol precursors bearing an N-acyl oxazolidin-2-one in the α position. From these alcohols were also obtained halogenated pentasubstituted tetrahydropyrans as well as 2,3,4,5-tetrasubstituted tetrahydrofurans, shedding light on the mechanism of the process. Computational studies were consistent with the experimental findings, and this innovative Evans aldol-Prins strategy was performed for the preparation of a battery of more than 30 densely substituted tetrahydropyrans, unprecedentedly fused to a 1,3-oxazinane-2,4-dione ring, both in a racemic fashion and in an enantiomeric fashion. These novel molecules were successfully submitted to several transformations to permit simple access to a variety of differently functionalized tetrahydropyrans. Most of these unique molecules were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria and the yeast Candida albicans, and some structure-activity relationships were established.Facultad de Ciencias ExactasLaboratorio de Investigación y Desarrollo de Bioactivo

Combined sensitivity of JUNO and KM3NeT/ORCA to the neutrino mass ordering

[EN] This article presents the potential of a combined analysis of the JUNO and KM3NeT/ORCA experiments to determine the neutrino mass ordering. This combination is particularly interesting as it significantly boosts the potential of either detector, beyond simply adding their neutrino mass ordering sensitivities, by removing a degeneracy in the determination of ¿m² between the two experiments when assuming the wrong ordering. The study is based on the latest projected performances for JUNO, and on simulation tools using a full Monte Carlo approach to the KM3NeT/ORCA response with a careful assessment of its energy systematics. From this analysis, a 5¿ determination of the neutrino mass ordering is expected after 6 years of joint data taking for any value of the oscillation parameters. This sensitivity would be achieved after only 2 years of joint data taking assuming the current global best-fit values for those parameters for normal ordering.The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Generalitat Valenciana: Prometeo (PROMETEO/2020/019), Grisolia (ref. GRISOLIA/2018/119) and GenT (refs. CIDEGENT/2018/034,/2019/043,/2020/049) programs, Junta de Andalucia (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 101025085), Spain.Aiello, S.; Albert, A.; Alshamsi, M.; Alves Garre, S.; Aly, Z.; Ambrosone, A.; Ameli, F.... (2022). Combined sensitivity of JUNO and KM3NeT/ORCA to the neutrino mass ordering. Journal of High Energy Physics (Online). (3):1-31. https://doi.org/10.1007/JHEP03(2022)055131

Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Methods: Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. Results: The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN. Conclusions: A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM