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The transport of nutrients across the placenta involves trophoblast cell specific transporters modulated through the mammalian target of rapamycin (mTOR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast cell migration and invasion. Here we explored the effect of VIP on glucose and System A amino acid uptake by human trophoblast-derived cells (Swan 71 and BeWo cell lines). VIP activated D-glucose specific uptake in single cytotrophoblast cells in a concentration-dependent manner through PKA, MAPK, PI3K and mTOR signalling pathways. Glucose uptake was reduced in VIP-knocked down cytotrophoblast cells. Also, VIP stimulated System A amino acid uptake and the expression of GLUT1 glucose transporter and SNAT1 neutral amino acid transporter. VIP increased mTOR expression and mTOR/S6 phosphorylation whereas VIP silencing reduced mTOR mRNA and protein expression. Inhibition of mTOR signalling with rapamycin reduced the expression of endogenous VIP and of VIP-induced S6 phosphorylation. Our findings support a role of VIP in the transport of glucose and neutral amino acids in cytotrophoblast cells through mTOR-regulated pathways and they are instrumental for understanding the physiological regulation of nutrient sensing by endogenous VIP at the maternal-foetal interface. Fil: Merech, Fátima Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Soczewski, Elizabeth Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

El caso versa sobre la demanda de un título colectivo sobre su territorio ancestral por parte de 132 comunidades indígenas pertenecientes a los pueblos Wichí (Mataco), Iyjwaja (Cho-rote), Komlek (Toba), Niwackle (Chulupí) y Tapy’y (Tapiete), nucleadas en la asociación Lhaka Honhat. En términos generales, lo que la Corte debía determinar no era la existencia o no del derecho de las comunidades a sus tierras, derecho que había sido reconocido por el propio Estado argentino, sino más bien si la acción de este último había sido suficiente para respetar y garantizar el derecho de las comunidades indígenas a la propiedad colectiva sobre sus tierras (Cabrera, Cerqueira y Herencia, 2020). Luego de evaluar las solicitudes, argumentos y pruebas presentados por las partes, la Corte estableció en su sentencia la responsabilidad internacional de la República Argentina. A lo fines de ordenar el análisis del caso, podemos desglosar el hecho ilícito internacional del Estado en los dos elementos definidos por el régimen consuetudinario de responsabilidad internacional de los Estados., Instituto de Relaciones Internacionales

¿Hay una relación necesaria entre violencia y mercados de drogas ilícitas? ¿Qué pasa con la violencia que no es tapa? Angélica Durán Martínez (2018) señala que, frecuentemente, nuestra comprensión de la violencia narco no sólo se rige por estereotipos, sino también por centrarse en situaciones extremas. Estos sesgos, muy propios (pero no exclusivos) del tratamiento mediático de la cuestión, impiden detectar una trama más compleja y las modulaciones en los patrones de violencia. En esta breve nota pretendo recuperar el marco conceptual propuesto por la autora para repensar las conexiones entre narcotráfico y violencia, a partir de dos elementos clave: la desagregación de la violencia y un encuadre de “economía política” de ésta., Instituto de Relaciones Internacionales

An extensive experimental study of the shapes of two-dimensional bipolar droplets of the chromonic N nematic phase of disodium cromoglycate (DSCG) sandwiched between glass plates, by Y.-K. Kim et al. was published in [Y.-K. Kim et al., J. Phys.: Condens. Matter 25, 404202 (2013)]. The paper includes a mathematical model of this system. We have extended this study by further theoretical modelling. Our results are in good, quantitative agreement with the experimental data. The model has produced what promises to be a more accurate estimate for the isotropic surface ten- sion at the nematic/isotropic solution interface—and predicts a regime of shape bistability (which has not yet been observed) for larger droplets, where tactoids (pointed, zeppelin-shaped droplets) and smooth-edged discoids can coexist in equilibrium. The general method presented in this paper is also applied to the tactoids formed by F-actin filaments in solution, for which an estimate is given for the value of the isotropic surface tension at the nematic/isotropic interface.

Glucose uptake by the placenta and its transfer to the fetus is a finely regulated process required for placental and fetal development. Deficient placentation is associated with pregnancy complications such as fetal growth restriction (FGR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast metabolism and function. Here we compared glucose uptake and transplacental transport in vivo by VIP-deficient placentas from normal or VIP-deficient maternal background. The role of endogenous VIP in placental glucose and amino acid uptake was also investigated. Wild type C57BL/6 (WT) or VIP+/- (VIP HT) females were mated with WT, VIP knock-out (VIP KO) or VIP HT males. Glucose uptake and transplacental transport were evaluated by the injection of the fluorescent d-glucose analogue 2-NBDG in pregnant mice at gestational day (gd) 17.5. Glucose and amino acid uptake in vitro by placental explants were measured with 2-NBDG or 14C-MeAIB respectively. In normal VIP maternal background, fetal weight was reduced in association with placental VIP deficiency, whereas placental weight was unaltered. Paradoxically, VIP+/- placentas presented higher glucose uptake and higher gene expression of GLUT1 and mTOR than VIP+/+ placentas. However, in a maternal VIP-deficient environment placental uptake and transplacental transport of glucose increased while fetal weights were unaffected, regardless of feto-placental genotype. Results point to VIP-deficient pregnancy in a normal background as a suitable FGR model with increased placental glucose uptake and transplacental transport. The apparently compensatory actions are unable to sustain normal fetal growth and could result in complications later in life.

Tactoids are pointed, spindlelike droplets of nematic liquid crystal in an isotropic fluid. They have long been observed in inorganic and organic nematics, in thermotropic phases as well as lyotropic colloidal aggregates. The variational problem of determining the optimal shape of a nematic droplet is formidable and has only been attacked in selected classes of shapes and director fields. Here, by considering a special class of admissible solutions for a bipolar droplet, we study the prevalence in the population of all equilibrium shapes of each of the three that may be optimal (tactoids primarily among them). We show how the prevalence of a shape is affected by a dimensionless measure $\ensuremath{\alpha}$ of the drop's volume and the ratios ${k}_{24}$ and ${k}_{3}$ of the saddle-splay constant ${K}_{24}$ and the bending constant ${K}_{33}$ of the material to the splay constant ${K}_{11}$. Tactoids, in particular, prevail for $\ensuremath{\alpha}⪅16.2+0.3{k}_{3}\ensuremath{-}(14.9\ensuremath{-}0.1{k}_{3}){k}_{24}$. Our class of shapes (and director fields) is sufficiently different from those employed so far to unveil a rather different role of ${K}_{24}$.

Additional file 1.

Aim: To explore the functional profile of circulating monocytes and decidual macrophages at term human pregnancy and their contribution to tissue repair upon stimulation ex vivo with decidual factors and the vasoactive intestinal peptide (VIP). Methods: Peripheral blood monocytes were isolated from pregnant and non-pregnant volunteers and tested in vitro with decidual explants from term placenta and VIP. The effect of VIP on decidual explants and the effect of its conditioned media on monocytes or decidual macrophages isolated by magnetic beads was carried out by RT-qPCR and ELISA for cytokines expression and release. Migration assays were performed in transwell systems. Efferocytosis was assessed in monocytes or decidual macrophages with CFSE-labelled autologous apoptotic neutrophils and quantified by flow cytometry. Monocyte and decidual macrophages wound healing capacity was evaluated using human endometrial stromal cell monolayers. Immunohistochemistry was performed in serial tissue sections of different placentas. Results: VIP is expressed in the villi as well as in trophoblast giant cells distributed within the decidua of term placenta. VIP induced the expression of antiinflmammatory markers and monocyte chemoattractant CCL2 and CCL3 in decidual tissues. Monocytes presented higher migration towards decidual explants than CD4 and CD8 cells. VIP-conditioned monocytes displayed an enhanced efferocytosis and wound healing capacity comparable to that of decidual macrophages. Moreover limited efferocytosis of pregnant women monocytes was restored by VIP-induced decidual factors. Conclusion: Results show the conditioning of monocytes by decidual factors and VIP to sustain processes required for tissue repair and homeostasis maintenance in term placenta. Fil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Fernández, Laura del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fátima Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Weingrill Barbano, Rodrigo. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil Fil: Correa Silva, Simone. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil Fil: Izbizky, Gustavo Hernán. Hospital Italiano; Argentina Fil: Abasolo, José I.. Hospital Italiano; Argentina Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Bevilaqcua, Estela. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Este libro es el resultado de un proyecto colectivo, iniciado a partir de las ponencias del I Congreso de Derechos Humanos desde América Latina, realizado en la Universidad Nacional de Rosario (UNR) en agosto de 2019. Participaron del trabajo los siguientes espacios institucionales: Cátedra de Pensamiento Constitucional Latinoamericano (UNR), Instituto de Cooperación Latinoamericana (UNR), Área de Derechos Humanos (UNR) y Maestría en Derechos Humanos (UASLP). Universidad Nacional de Rosario

IntroductionThe effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain.Methods and analysisThe Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60.Ethics and disseminationROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results.

Global efforts and challenges in addressing the burden of adolescent HIV have demonstrated language matters. Presently, progress is hindered by the unhelpful and influential use of outdated, inadvertently stigmatising terminology. We propose universal adoption of the terms ‘recently acquired HIV’ rather than ‘behaviourally-acquired,’ and ‘treatment switch’ rather than ‘treatment failure.’

Decidualization denotes the reprogramming of endometrial stromal cells that includes the secretion of different mediators like cytokines, chemokines, and the selective recruitment of immune cells. This physiological process involves changes in the secretome of the endometrial stromal cells leading to the production of immunomodulatory factors. The increased amount of protein secretion is associated with a physiological endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR), allowing the expansion of ER and the machinery to assist the protein folding. Notably, the signaling pathways involved in the ER stress and the UPR are interconnected with the onset of a sterile inflammatory response, as well as with angiogenesis. Both of these processes have a key role in decidualization and placentation, therefore, alterations in them could lead to pregnancy complications. In this review, we will discuss how the induction of ER stress and the UPR processes that accompanies the decidualization are associated with embryo implantation and whether they might condition pregnancy outcome. The ER stress activates/triggers sensing proteins which, among others, induces kinase/RNAse-TXNIP expression, activating the NLRP3 inflammasome. This multiprotein system allows caspase-1 activation, which catalyzes the cleavage of the inactive IL-1β proform toward the mature secretory form, with pro-implantatory effects. However, the sterile inflammatory response should be later controlled in favor of a tolerogenic microenvironment to sustain pregnancy. In accordance, alterations of the ER stress and UPR processes can be reflected in recurrent implantation failures (RIF), recurrent pregnancy loss (RPL), or complications associated with deficient placentation, such as preeclampsia (PE). Fil: Soczewski, Elizabeth Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gallino, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Fernández, Laura del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gori, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Immune homeostasis maintenance throughout pregnancy is critical for normal fetal development. Trophoblast cells differentiate into an invasive phenotype and contribute to the transformation of maternal arteries and the functional shaping of decidual leukocyte populations. Insufficient trophoblast invasion, inadequate vascular remodeling, and a loss of immunologic homeostasis are associated with pregnancy complications, such as preeclampsia and intrauterine growth restriction. Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide synthetized in trophoblasts at the maternal–placental interface. It regulates the function of trophoblast cells and their interaction with decidual leukocytes. By means of a murine model of pregnancy in normal maternal background with VIP-deficient trophoblast cells, here we demonstrate that trophoblast VIP is critical for trophoblast function: VIP gene haploinsufficiency results in lower matrix metalloproteinase 9 expression, and reduced migration and invasion capacities. A reduced number of regulatory T cells at the implantation sites along with a lower expression of proangiogenic and antiinflammatory markers were also observed. Findings detected in the implantation sites at early stages were followed by an abnormal placental structure and lower fetal weight. This effect was overcome by VIP treatment of the early pregnant mice. Our results support the relevance of trophoblast-synthesized VIP as a critical factor in vivo for trophoblast-cell function and immune homeostasis maintenance in mouse pregnancy. Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gallino, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Calo, Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fátima Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Ochoa, Federico Claudio. Universidad de Buenos Aires; Argentina Fil: Zotta, Elsa. Universidad de Buenos Aires; Argentina Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Waschek, James. Jane & Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

A network of cell-cell communications through contact and soluble factors supports the maternal-placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti-inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast-immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation.

Global health priorities are being set to address questions on adherence to HIV antiretroviral therapy in adolescence. Few studies have explored young people’s perspectives on the complex host of social and relational challenges they face in dealing with their treatment in secret and their condition in silence. In redressing this, we present findings from a longitudinal qualitative study with young people living with HIV in the UK, Ireland, US, and Uganda, embedded within the BREATHER international clinical trial. Drawing from Goffman’s notion of stigma, we analyze relational dynamics in HIV clinics, as rare spaces where HIV is “known,” and how young people’s relationships may be threatened by non-adherence to treatment. Young people’s reflections on and strategies for maintaining their reputation as patients raise questions about particular forms of medicalization of HIV and the moralization of treatment adherence that affect them, and how these may restrict opportunities for care across the epid...

Hace menos de un siglo que la población dispone de medicinas, vacunas y diferentes tratamientos avalados por la evidencia científica y utilizados por la medicina actual; estos avances han permitido aumentar considerablemente los años de esperanza de vida en general. La pregunta que surge es, ¿cómo se solucionaban o aliviaban las dolencias en épocas más remotas? Podemos pensar que utilizaban otros tipos de productos obtenidos de la naturaleza: plantas, hierbas, hongos, sustancias de origen animal, etc. Este sistema tradicional basado en la utilización de productos naturales no se perdió, sino que se sustenta en el saber popular e implica un conjunto de conocimientos, creencias, prácticas y recursos provenientes de este saber en un contexto sociocultural particular, y de los que hace uso la población de un colectivo para resolver de forma empírica algunos problemas de salud a pesar de la existencia y del alcance de la medicina científica (Menéndez, et al, 1994). El objetivo de la investigación es relevar las plantas que se utilizan como remedios naturales, para qué tipo de dolencias, y describir la población usuaria de esta opción en comparación con los que prefieren el uso de medicamentos farmacéuticos. Para la siguiente investigación se recolectaron datos mediante encuestas anónimas. Observamos cuales son los RN más utilizados y para qué tipo de dolencias son utilizados. Determinamos los motivos por los cuales se elige esta opción frente a medicamentos de farmacia; estudiamos los grupos en ambos casos sin encontrar diferencias significativas. La población con menos ingresos y que se atiende en hospitales públicos utiliza los RN de la misma forma que los de ingresos superiores con prepagas u obra social. El hábito de usar los RN tiene un componente que se transmite de generación en generación. Se observaron diferencias significativas, siendo mayor el uso de RN cuando sus padres también lo usaban. Nuestra hipótesis es que hay una tendencia a la medicalización; se exige una respuesta rápida y efectiva. Este comportamiento lleva a una pérdida del uso de RN y mengua su transmisión a las siguientes generaciones. Fil: Balducci D’Orta, María Laura. Universidad Nacional de La Matanza; Argentina Fil: Calo, Guillermina. Universidad Nacional de La Matanza; Argentina Fil: Coria Costenla, Vanesa. Universidad Nacional de La Matanza; Argentina Fil: Dastugue, Milagros. Universidad Nacional de La Matanza; Argentina Fil: Lang, Fabián. Universidad Nacional de La Matanza; Argentina Fil: Grasso, Esteban. Universidad Nacional de La Matanza; Argentina Fil: Paparini, Daniel. Universidad Nacional de La Matanza; Argentina Fil: Savino, Antonio. Universidad Nacional de La Matanza; Argentina Fil: Patrinos, Agustín. Universidad Nacional de La Matanza; Argentina Fil: Pathauer, Florencia. Universidad Nacional de La Matanza; Argentina Fil: Rodríguez, Saúl Marcelo. Universidad Nacional de La Matanza; Argentina Fil: Del Pino, Verónica. Universidad Nacional de La Matanza; Argentina

BackgroundBullying, aggression and violence among children and young people are some of the most consequential public mental health problems.ObjectivesThe INCLUSIVE (initiating change locally in bullying and aggression through the school environment) trial evaluated the Learning Together intervention, which involved students in efforts to modify their school environment using restorative approaches and to develop social and emotional skills. We hypothesised that in schools receiving Learning Together there would be lower rates of self-reported bullying and perpetration of aggression and improved student biopsychosocial health at follow-up than in control schools.DesignINCLUSIVE was a cluster randomised trial with integral economic and process evaluations.SettingForty secondary schools in south-east England took part. Schools were randomly assigned to implement the Learning Together intervention over 3 years or to continue standard practice (controls).ParticipantsA total of 6667 (93.6%) students participated at baseline and 5960 (83.3%) students participated at final follow-up. No schools withdrew from the study.InterventionSchools were provided with (1) a social and emotional curriculum, (2) all-staff training in restorative approaches, (3) an external facilitator to help convene an action group to revise rules and policies and to oversee intervention delivery and (4) information on local needs to inform decisions.Main outcome measuresSelf-reported experience of bullying victimisation (Gatehouse Bullying Scale) and perpetration of aggression (Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale) measured at 36 months. Intention-to-treat analysis using longitudinal mixed-effects models.ResultsPrimary outcomes – Gatehouse Bullying Scale scores were significantly lower among intervention schools than among control schools at 36 months (adjusted mean difference –0.03, 95% confidence interval –0.06 to 0.00). There was no evidence of a difference in Edinburgh Study of Youth Transitions and Crime scores. Secondary outcomes – students in intervention schools had higher quality of life (adjusted mean difference 1.44, 95% confidence interval 0.07 to 2.17) and psychological well-being scores (adjusted mean difference 0.33, 95% confidence interval 0.00 to 0.66), lower psychological total difficulties (Strengths and Difficulties Questionnaire) score (adjusted mean difference –0.54, 95% confidence interval –0.83 to –0.25), and lower odds of having smoked (odds ratio 0.58, 95% confidence interval 0.43 to 0.80), drunk alcohol (odds ratio 0.72, 95% confidence interval 0.56 to 0.92), been offered or tried illicit drugs (odds ratio 0.51, 95% confidence interval 0.36 to 0.73) and been in contact with police in the previous 12 months (odds ratio 0.74, 95% confidence interval 0.56 to 0.97). The total numbers of reported serious adverse events were similar in each arm. There were no changes for staff outcomes. Process evaluation – fidelity was variable, with a reduction in year 3. Over half of the staff were aware that the school was taking steps to reduce bullying and aggression. Economic evaluation – mean (standard deviation) total education sector-related costs were £116 (£47) per pupil in the control arm compared with £163 (£69) in the intervention arm over the first two facilitated years, and £63 (£33) and £74 (£37) per pupil, respectively, in the final, unfacilitated, year. Overall, the intervention was associated with higher costs, but the mean gain in students’ health-related quality of life was slightly higher in the intervention arm. The incremental cost per quality-adjusted life year was £13,284 (95% confidence interval –£32,175 to £58,743) and £1875 (95% confidence interval –£12,945 to £16,695) at 2 and 3 years, respectively.LimitationsOur trial was carried out in urban and periurban settings in the counties around London. The large number of secondary outcomes investigated necessitated multiple statistical testing. Fidelity of implementation of Learning Together was variable.ConclusionsLearning Together is effective across a very broad range of key public health targets for adolescents.Future workFurther studies are required to assess refined versions of this intervention in other settings.Trial registrationCurrent Controlled Trials ISRCTN10751359.FundingThis project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full inPublic Health Research; Vol. 7, No. 18. See the NIHR Journals Library website for further project information. Additional funding was provided by the Educational Endowment Foundation.

Population genetic studies of Trichomonas vaginalis have detected high genetic diversity associated with phenotypic differences in clinical presentations. In this study, microscopy and next generation-multi-locus sequence typing (NG-MLST) were used to identify and genetically characterise T. vaginalis isolates from patients in Australia and Ghana. Seventy-one polymorphic nucleotide sites, 36 different alleles, 48 sequence types, 24 of which were novel, were identified among 178 isolates, revealing a geneticallly diverse T. vaginalis population. Polymorphism was found at most loci, clustering genotypes into eight groups among both Australian and Ghanaian isolates, although there was some variation between countries. The number of alleles for each locus ranged from two to nine. Study results confirmed geographic expansion and diversity of the T. vaginalis population. Two-type populations in almost equal frequencies and a third unassigned group were identified in this study. Linkage disequilibrium was observed, suggesting T. vaginalis population is highly clonal. Multillocus disequilibrium was observed even when analysing clades separately, as well as widespread clonal genotypes, suggesting that there is no evidence of recent recombination. A more comprehensive study to assess the extent of genetic diversity and population structure of T. vaginalis and their potential impact on varied pathology observed among infected individuals is recommended.

Background Schools struggle to timetable health education. Interventions integrating academic and health education to reduce substance use and violence offer promise. No current systematic reviews examine such interventions. Objectives To review evidence to explore the following questions: (1) what types of interventions integrating health and academic education in schools serving those aged 4–18 years have been evaluated? (2) What theories of change inform these interventions? (3) What factors facilitate or limit the successful implementation and receipt of such interventions, and what are the implications for the delivery of such implementations in the UK? (4) How effective are such interventions in reducing smoking and violence and the use of alcohol and drugs, and at increasing attainment? Does this vary by students’ sociodemographic characteristics? (5) What factors appear to influence the effectiveness of such interventions? Data sources In total, 19 databases were searched from 18 November to 22 December 2015, updating searches for outcome evaluations for violence on 28 February 2018 and for substance use on 14 May 2018. References were extracted from included studies and authors contacted. Review methods Included studies reported on theories of change, and process or outcome evaluations of interventions that integrated academic and health education to reduce substance use and/or violence. References were screened on the title/abstract and then on the full report. Data extraction and appraisal used Cochrane, Evidence for Policy and Practice Information Centre and other established tools. Theories of change and process data were qualitatively synthesised. Outcome evaluations were synthesised narratively and meta-analytically. Results In total, 78,451 unique references were originally identified and 62 reports included. Search updates on 28 February and 14 May 2018 retrieved a further 2355 and 1945 references, respectively, resulting in the inclusion of six additional reports. Thirty-nine reports described theories, 16 reports (15 studies) evaluated process and 41 reports (16 studies) evaluated outcomes. Multicomponent interventions are theorised to erode ‘boundaries’ (strengthen relationships) between academic and health education, teachers and students, behaviour in classrooms and in the wider school, and schools and families. Teachers, pro-social peers and parents are theorised to act as role models and reinforcers of healthy behaviours learnt in lessons. There was clear evidence that interventions are facilitated by supportive senior management and alignment with the schools’ ethos, collaborative and supportive teaching environments, and positive pre-existing student, teacher and parent attitudes towards interventions. The barriers were overburdened teachers who had little time to both learn and implement integrated curricula. The strongest evidence for effectiveness was found for the reduction of substance use in school key stages (KSs) 2 and 3. For example, a meta-analysis for substance use at KS3 reported a mean difference of –0.09 (95% confidence interval –0.17 to –0.01). A meta-analysis for effectiveness in reducing violence victimisation in KS2 found no effect. There was mixed evidence for effects on academic outcomes, with meta-analysis precluded by methodological heterogeneity. Limitations Study quality was variable. Integration was sometimes not emphasised in theories of change. Conclusions These interventions are undertheorised but involve multiple forms of boundary erosion. There is clear evidence of characteristics affecting implementation. Interventions are likely to have the greatest impact on substance use. These programmes may be effective in reducing substance use but do not appear to reduce violence and findings on educational impacts are mixed. Future work Future evaluations should assess interventions with clearer theories of change and examine academic outcomes alongside violence and substance use outcomes. Study registration This study is registered as PROSPERO CRD42015026464. Funding The National Institute for Health Research Public Health Research programme.

We should focus on working with families, schools, communities, and other organisations to protect our young people from becoming embroiled in violent crime

Normal placentation entails highly regulated interactions of maternal leukocytes with vascular and trophoblast cells to favor vascular transformation. Neutrophil activation and neutrophil extracellular trap (NET) formation associate with poor placentation and severe pregnancy complications. To deepen into the mechanisms of trophoblast-neutrophil interaction, we explored the effects of NETs on trophoblast cell function and, conversely, whether trophoblast cell-derived factors condition neutrophils to favor angiogenesis and anti-inflammatory signals required for fetal growth. NETs isolated from activated neutrophils hindered trophoblast cell migration. Trophoblast conditioned media prevented the effect as well as the vasoactive intestinal peptide (VIP) known to regulate trophoblast and neutrophil function. On the other hand, factors released by trophoblast cells and VIP shaped neutrophils to a proangiogenic profile with increased vascular endothelial growth factor synthesis and increased capacity to promote vascular transformation. Results presented here provide novel clues to reconstruct the interaction of trophoblast cells and neutrophils in vivo during placentation in humans. Fil: Calo, Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Keitelman, Irene Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Trevani, Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Pérez Leirós, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

We should focus on working with families, schools, communities and other organisations to protect our young people from becoming embroiled in violent crime