Structural aspects of Hamilton–Jacobi theory

The final publication is available at Springer via http://dx.doi.org/10.1142/S0219887816500171In our previous papers [11, 13] we showed that the Hamilton–Jacobi problem can be regarded as a way to describe a given dynamics on a phase space manifold in terms of a family of dynamics on a lower-dimensional manifold. We also showed how constants of the motion help to solve the Hamilton–Jacobi equation. Here we want to delve into this interpretation by considering the most general case: a dynamical system on a manifold that is described in terms of a family of dynamics (‘slicing vector fields’) on lower-dimensional manifolds. We identify the relevant geometric structures that lead from this decomposition of the dynamics to the classical Hamilton– Jacobi theory, by considering special cases like fibred manifolds and Hamiltonian dynamics, in the symplectic framework and the Poisson one. We also show how a set of functions on a tangent bundle can determine a second-order dynamics for which they are constants of the motion.Peer ReviewedPostprint (author's final draft

Controlling the Adsorption and Release of Ocular Drugs in Metal–Organic Frameworks: Effect of Polar Functional Groups

A series of UiO-66 materials with different functional groups (−H, −NH2, and −NO2) have been evaluated for the adsorption and release of a common ocular drug such as brimonidine tartrate. UiO-66 samples were synthesized under solvothermal conditions and activated by solvent exchange with ethanol. Experimental results suggest that the incorporation of surface functionalities gives rise to the development of structural defects (missing linker defects) but without altering the basic topology of the UiO-66 framework. These defects improve the adsorption performance of the parent metal–organic framework (MOF), while the bulkier functionalities infer slower release kinetics, with the associated benefits for prolonged delivery of brimonidine. Among the evaluated MOFs, defective UiO-66-NO2 can be proposed as the most promising candidate due to the combination of a larger brimonidine volumetric uptake (680 mg/cm3), a prolonged delivery (period of up to 25 days), a small particle size, and a larger instability. Contrariwise, at high concentrations UiO-66-NO2 has higher toxicity toward human retinal pigment epithelium cells (ARPE-19) compared to the pure and NH2-functionalized UiO-66.Authors would like to acknowledge financial support from the Ministerio de Ciencia e Innovación (Project PID2019-108453GB-C21), H2020 (Project MSCA-RISE-2016/NanoMed) and Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital (Project CIPROM/2021/022)

Untargeted metagenomic sequencing identifies Toscana virus in patients with idiopathic meningitis, southern Spain, 2015 to 2019

Background: Various pathogens, including bacteria, fungi, parasites, and viruses can lead to meningitis. Among viruses causing meningitis, Toscana virus (TOSV), a phlebovirus, is transmitted through sandfly bites. TOSV infection may be suspected if patients with enterovirus- and herpesvirus-negative aseptic (non-bacterial) meningitis recall recent insect bites. Other epidemiological factors (season, rural area) may be considered. The broad range of possible meningitis aetiologies poses considerable diagnosis challenges. Untargeted metagenomic next-generation sequencing (mNGS) can potentially identify pathogens, which are not considered or detected in routine diagnostic panels. Aim: In this retrospective, single-centre observational study, we investigated mNGS usefulness to understand the cause of meningitis when conventional approaches fail. Methods: Cerebrospinal fluid (CSF) samples from patients hospitalised in southern Spain in 2015-2019 with aseptic meningitis and no aetiology found by conventional testing, were subjected to mNGS. Patients' demographic characteristics had been recorded and physicians had asked them about recent insect bites. Obtained viral genome sequences were phylogenetically analysed. Results: Among 23 idiopathic cases, TOSV was identified in eight (all male; median age:  39 years, range: 15-78 years). Five cases lived in an urban setting, three occurred in autumn and only one recalled insect bites. Phylogenetic analysis of TOSV segment sequences supported one intra-genotype reassortment event. Conclusions: Our study highlights the usefulness of mNGS for identifying viral pathogens directly in CSF. In southern Spain, TOSV should be considered regardless of recalling of insect bites or other epidemiological criteria. Detection of a disease-associated reassortant TOSV emphasises the importance of monitoring the spread and evolution of phleboviruses in Mediterranean countries.ESL laboratory received funding from Institut Pasteur, from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005), from the NIH PICREID program (Award Number U01AI151758) and from the Labex IBEID (ANR-10-LABX-62-IBEID). MDFG acknowledges funding from the Junta de Andalucia (PI-0216-2019) and Instituto de Salud Carlos III (Acción Estratégica en Salud Intramural PI20CIII/00005).S

A State‐of‐the‐Art Review of Indigenous Peoples and Environmental Pollution

Indigenous peoples (IPs) worldwide are confronted by the increasing threat of pollution. Based on a comprehensive review of the literature (n = 686 studies), we present the current state of knowledge on: 1) the exposure and vulnerability of IPs to pollution; 2) the environmental, health, and cultural impacts of pollution upon IPs; and 3) IPs' contributions to prevent, control, limit, and abate pollution from local to global scales. Indigenous peoples experience large burdens of environmental pollution linked to the expansion of commodity frontiers and industrial development, including agricultural, mining, and extractive industries, as well as urban growth, waste dumping, and infrastructure and energy development. Nevertheless, IPs are contributing to limit pollution in different ways, including through environmental monitoring and global policy advocacy, as well as through local resistance toward polluting activities. This work adds to growing evidence of the breadth and depth of environmental injustices faced by IPs worldwide, and we conclude by highlighting the need to increase IPs' engagement in environmental decision‐making regarding pollution control. Integr Environ Assess Manag 2020;16:324–341. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)Peer reviewe

Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma

Adrenal gland diseases; Cancer genomics; Prognostic markersMalalties de les glàndules suprarenals; Genòmica del càncer; Marcadors pronòsticsEnfermedades de las glándulas suprarrenales; Genómica del cáncer; Marcadores pronósticosThe mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.This work was supported by Project PI17/01796 and PI20/01169 to M.R. [Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofinanciado a través del Fondo Europeo de Desarrollo Regional (FEDER)], Paradifference Foundation [no grant number applicable to M.R.], Pheipas Association [no grant number applicable to M.R.], the Clinical Research Priority Program of the University of Zurich for the CRPP HYRENE to F.B., the Deutsche Forschungsgemeinschaft (DFG) within the CRC/Transregio 205/1 (Project No. 314061271-TRR205 to to F.B., M.F., N.B., and G.E.) and the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (Project No. PID2019-111356RA-I00 to G.M.). B.C. was supported by the Rafael del Pino Foundation (Becas de Excelencia Rafael del Pino 2017). A.M.M.-M. was supported by CAM (S2017/BMD-3724; TIRONET2-CM). A.F.-S. and J.L. received the support of a fellowship from La Caixa Foundation (ID 100010434; LCF/BQ/DR21/11880009 and LCF/BQ/DR19/11740015, respectively). M.M., S.M., and M.S. were supported by the Spanish Ministry of Science, Innovation and Universities “Formación del Profesorado Universitario— FPU” fellowship with ID number FPU18/00064, FPU19/04940 and FPU16/05527. A.D.-T. is supported by the Centro de Investigacion Biomédica en Red de Enfermedades Raras (CIBERER). L.J.L.-G. was supported both by the Banco Santander Foundation and La Caixa Postdoctoral Junior Leader Fellowship (LCF/BQ/PI20/11760011). C.M.-C. was supported by a grant from the AECC Foundation (AIO15152858 MONT). We thank the Spanish National Tumor Bank Network (RD09/0076/00047) for the support in obtaining tumorsamples and all patients, physicians and tumor biobanks involved in the study

IFNL3 rs12980275 Polymorphism Predicts Septic Shock-Related Death in Patients Undergoing Major Surgery: A Retrospective Study

Interferon lambda 3 (IFNL3, previously called IL-28B) is a cytokine with effects against viral and bacterial pathogens. We aimed to analyze the IFNL3 rs12980275 SNP in patients who underwent major surgery, in order to establish its relationship with susceptibility to septic shock and septic shock-related death in these patients. We performed a case-control study on 376 patients to establish the association between IFNL3 rs12980275 SNP and the susceptibility to develop septic shock. Besides, we performed a longitudinal study among 172 septic shock patients using survival analysis with one censoring point of 28-days mortality. The IFNL3 rs12980275 polymorphism was genotyped by Agena Bioscience's MassARRAY platform. IFNL3 rs12980275 polymorphism was not associated with higher susceptibility to infection and septic shock development. Regarding survival analysis, the Kaplan-Meier analysis showed that patients with IFNL3 rs12980275 AA genotype had higher survival than patients with GG genotype (p = 0.003). The Cox regression analysis adjusted by the most relevant clinical and epidemiological characteristics showed that the GG genotype (recessive model) and the presence of the G allele (additive model) were associated with higher risk of death [adjusted hazard ratio (aHR) = 2.15, p = 0.034; aHR = 1.50, p = 0.030, respectively]. In conclusion, IFNL3 rs12980275 polymorphism was associated with septic shock-related death in patients who underwent major surgery. The A allele was linked to protection, and the G allele was associated with an increased risk of death. This is a first preliminary study that suggests for the first time a role of IFNL3 polymorphisms in the prognosis of septic shock.This work has been supported by grants given by Instituto de Salud Carlos III (grant numbers PI15/01451 to ET), Gerencia de Salud, Consejería de Sanidad, Junta de Castilla y Leon (grant number GRS 463/A/10 and 773/A/13 to ET), and PFIZER (grant number CT25-ESP01-01 to SR). MJ-S and AF-R are supported by Instituto de Salud Carlos III (grant numbers CP17CIII/00007 and CP14CIII/00010, respectively).S

CEACAM7 polymorphisms predict genetic predisposition to mortality in post-surgical septic shock patients

We carried out a retrospective exploratory study on 173 patients who underwent major surgery and developed septic shock after surgery. Our findings suggest that CEACAM7 rs1001578, rs10409040, and rs889365 polymorphisms could influence septic shock-related death in individuals who underwent major surgery.This work has been supported by grants given by Instituto de Salud Carlos III (grant number PI15/01451 to ET), “Gerencia de Salud, Consejería de Sanidad, Junta de Castilla y Leon” [grant number GRS 463/A/10 and 773/A/13 to ET], and PFIZER [grant number CT25-ESP01-01 to SR]. MAJS and AFR are supported by “Instituto de Salud Carlos III” [grant numbers CP17CIII/00007 and CP14CIII/00010, respectively]S

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento del Magdalena.

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento del Magdalena.El presente trabajo es producto del Diplomado de Acompañamiento de acción Psicosocial en el escenarios de violencia, se sustenta en la búsqueda de la comprensión y el análisis contextual pormenorizado a partir de la integración de procesos académicos que articulan teorías, metodologías y técnicas para el diagnóstico, acompañamiento y evaluación de situaciones traumáticas, crisis y violencias a las que se ve expuesta una persona, grupo o institución. La primera actividad se realiza de manera individual, eligiendo un caso descrito para analizarlo y luego realizar un ejercicio respondiendo preguntas que lo llevan a comprender más la temática de violencia hacia un individuo y la manera cómo afronta los problemas físicos, psicológicos y sociales. Luego de manera colaborativa se realiza un análisis de un caso en particular donde relatan el caso de una comunidad que afronta problemas de conflicto armado y las consecuencias de la misma; abordando problemáticas psicosociales generados por el desplazamiento, muerte, inclusión social, todos inherentes al conflicto armado. Teniendo en cuenta los contenidos propuestos en las unidades prácticas, en el presente trabajo del Diplomado de profundización en escenarios de violencia se abarcan los contextos del enfoque narrativo, los cuales se trabajaron en distintos casos tomado de VOCES: Relatos de violencia y esperanza en Colombia, Editado por el Banco mundial en el año 2009,entre estos; Sé tomó el “caso de Carlos Arturo”, escogido por su gran importancia e impacto generado como resultado de víctimas de violencia en las minas anti personas, cambiando su vida completamente, mientras que en el caso propuesto en la Guía de Actividades “los pobladores de Cacarica” resalta los hechos violentos que vivieron estos pobladores, los cuales fueron obligados a desplazarse, dejando sus tierras dejando atrás sus sueños, con el fin de analizar, valorar y comprender los eventos psicosociales traumáticos desde una perspectiva psicológica, Los emergentes psicosociales aún siguen afectando a la población después de la violencia, permitiendo realizar un abordaje psicosocial, mediante el enfoque narrativo, el análisis de los relatos, las técnicas, acciones y por último las estrategias, argumentado por diferentes actores.The present work is the product of the Diploma of Accompanying of Psychosocial action in the scenarios of violence, it is based on the search for detailed understanding and contextual analysis based on the integration of academic processes that articulate theories, methodologies and techniques for diagnosis, accompanying and evaluation of traumatic situations, crises and violence to which a person, group or institution is exposed. The first activity is carried out individually, choosing a case described to analyze it and then perform an exercise answering questions that lead you to understand more the issue of violence towards an individual and the way he addresses physical, psychological and social problems. Then, in a collaborative way, an analysis of a particular case is carried out where it reports the case of a community that faces problems of armed conflict and its consequences; addressing psychosocial issues generated by displacement, death, social inclusion, all inherent in the armed conflict. Taking into account the contents proposed in the practical units, in the present work of the Diploma of deepening in scenarios of violence the contexts of the narrative approach are covered, which they worked on different cases taken from VOCES: Stories of violence and hope in Colombia, Edited by the World Bank in 2009, among these; they took the "case of Carlos Arturo", chosen for its great importance and impact generated as a result of victims of violence from anti-people mines, changing their lives completely, while in the case proposed in the Activities Guide "the inhabitants of Cacarica ”highlights the violent events that these settlers experienced, who were forced to move, leaving their lands leaving behind their dreams, in order to analyze, assess and understand traumatic psychosocial events from a psychological perspective. The purpose of this work is to analyze and understand them from our psychological perspective, seeking that emerging psychosocials still affect the population after the violence, allowing a psychosocial approach, through the narrative approach, the analysis of the stories, the techniques, actions and finally the strategies, argued by different participants

Next‐generation sequencing reveals that miR‐16‐5p, miR‐19a‐3p, miR‐451a, and miR‐25‐3p cargo in plasma extracellular vesicles differentiates sedentary young males from athletes

A sedentary lifestyle and Olympic participation are contrary risk factors for global mortality and incidence of cancer and cardiovascular disease. Extracellular vesicle miRNAs have been described to respond to exercise. No molecular characterization of young male sedentary people versus athletes is available; so, our aim was to identify the extracellular vesicle miRNA profile of chronically trained young endurance and resistance male athletes compared to their sedentary counterparts. A descriptive case–control design was used with 16 sedentary young men, 16 Olympic male endurance athletes, and 16 Olympic male resistance athletes. Next‐generation sequencing and RT‐qPCR and external and internal validation were performed in order to analyze extracellular vesicle miRNA profiles. Endurance and resistance athletes had significant lower levels of miR‐16‐5p, miR‐19a‐3p, and miR‐451a compared to sedentary people. Taking all together, exercise‐trained miRNA profile in extracellular vesicles provides a differential signature of athletes irrespective of the type of exercise compared to sedentary people. Besides, miR‐25‐3p levels were specifically lower in endurance athletes which defines its role as a specific responder in this type of athletes. In silico analysis of this profile suggests a role in adaptive energy metabolism in this context that needs to be experimentally validated. Therefore, this study provides for the first time basal levels of circulating miRNA in extracellular vesicles emerge as relevant players in intertissue communication in response to chronic exercise exposure in young elite male athletes

Structural basis for the biological relevance of the invariant apical stem in IRES-mediated translation

RNA structure plays a fundamental role in internal initiation of translation. Picornavirus internal ribosome entry site (IRES) are long, efficient cis-acting elements that recruit the ribosome to internal mRNA sites. However, little is known about long-range constraints determining the IRES RNA structure. Here, we sought to investigate the functional and structural relevance of the invariant apical stem of a picornavirus IRES. Mutation of this apical stem revealed better performance of G:C compared with C:G base pairs, demonstrating that the secondary structure solely is not sufficient for IRES function. In turn, mutations designed to disrupt the stem abolished IRES activity. Lack of tolerance to accept genetic variability in the apical stem was supported by the presence of coupled covariations within the adjacent stem–loops. SHAPE structural analysis, gel mobility-shift and microarrays-based RNA accessibility revealed that the apical stem contributes to maintain IRES RNA structure through the generation of distant interactions between two adjacent stem–loops. Our results demonstrate that a highly interactive structure constrained by distant interactions involving invariant G:C base pairs plays a key role in maintaining the RNA conformation necessary for IRES-mediated translation