Meconio y exposición prenatal a neurotóxicos

6 pages, 1 figures, 2 tables.[ESP] Introducción. La ubicuidad con la que se encuentran la mayoría de las substancias neurotóxicas en el medio ambiente implica a los pediatras en la necesidad de desarrollar métodos para medir la magnitud de la exposición durante los periodos vulnerables del desarrollo. Una forma útil de abordar este problema consiste en analizar muestras biológicas que acumulen las substancias neurotóxicas o sus metabolitos durante el periodo fetal.Método. Revisión bibliográfica sistemática de los últimos 20 años obtenida principalmente de Medline; Science Citation Index y Embase sobre los estudios con meconio como matriz de exposición prenatal a substancias neurotóxicas. El perfil de búsqueda utilizado fue: meconium, prenatal exposure, biological markers, matrices, environmental pollutants, nervous system poisonings, neurotoxicity sindromes. Hemos seleccionado los trabajos más importantes y de sus referencias se han obtenido los más relevantes de los años previos a la búsqueda.Resultados. Tradicionalmente, los esfuerzos para determinar la exposición fetal se han centrado en el análisis de sangre de cordón u orina de la madre o el neonato. El meconio es fácilmente disponible, es inerte, acumula los neurotóxicos y/o sus metabolitos desde la semana 12 de gestación donde quedan “fosilizados” hasta el nacimiento. Puede constituir un instrumento muy importante para investigar la exposición fetal a los distintos contaminantes ambientales y en particular a neurotóxicos.Conclusiones. Las exposiciones fetales a los distintos neurotóxicos estudiados a través de sangre materna, de cordón, pelo, uña, placenta y orina parecen ser menos predictivas sobre los efectos neurológicos que las mediciones de los mismos realizadas en meconio. Son necesarios más estudios en este campo.Implementar y desarrollar la medida en meconio de una amplia gama de sustancias neurotóxicas ayudará en la práctica pediátrica a una intervención e identificación temprana mostrando las exposiciones que puedan provocar daño y facilitando el desarrollo de medidas preventivas y rehabilitadoras.[ENG] Brackground. The environmental ubiquity of most neurotoxicants implies the pediatricians in the development of methods for exposure measurement during the vulnerable periods of development. The analysis of biological samples able to accumulate the neurotoxicant substances or its metabolites during the fetal period is a useful approach to fulfil this objective.Material and methods. A systematic literature review of the last 20 years in Medline, Science Citation Index and Embase on the studies with meconium like womb of prenatal exposure to neurotoxicants has been undertaken. The search profile was: “meconium”, “prenatal exposure”, “biological markers”, “matrices”, “environmental pollutants”, “nervous system poisonings”, “neurotoxicity sindromes”. We selected the most relevant articles and retrieved more from their references.Results. Traditionally, the efforts to determine the fetal exposure have been centered in the analysis of cord blood, urinates of the mother or of the neonato. Meconium is easily available, inert, accumulates the neurotoxicants and/or its metabolitos from week 12 of gestation where they are "fossilized" until the birth. It can constitute a very important instrument for the investigation of the fetal exposure to the different environmental pollutants and in particular to neurotoxicants.Conclusions. Foetal exposure to different neurotoxicants monitored from maternal blood, cord blood, hair, fingernail, placenta and urinates seem to be less predictive for neurological effects than meconium. However, more studies are needed to confirm this hypothesis.Implementation and measurement in meconium of a wide range of neurotoxic substances will be of help in the pediatric practice for intervention and early identification as it will reveal harmful exposures and facilitate the implementation of preventive measures.Los autores quieren expresar su agradecimiento a los miembros de la red de Investigación Colaborativa INMA, y en especial a Amparo Quiles Latorre, Elena Romero Aliaga y Sandra Pérez Aliaga, por su apoyo y colaboración en la realización del trabajo de campo; al equipo de enfermería de la 7ª, 8ª y 9ª de la maternidad del Hospital Materno-Infantil Universitario La Fe y a los recién nacidos y sus felices padres que con su colaboración y entusiasmo hacen posible llevar a término estos estudios.Peer reviewe

Bilateral Basal Ganglia Hemorrhage in a Patient with Confirmed COVID-19

Bilateral basal ganglia hemorrhage is exceedingly rare. To our knowledge, our patient is the first reported case of a confirmed coronavirus disease 2019 (COVID-19) patient who had bilateral basal ganglia hemorrhage. In the absence of other risk factors for bilateral deep cerebral involvement, we suspect that COVID-19 may be contributing to these rare pathologies. Most published data represent a correlation between COVID-19 and neurologic complications, and more research is still needed to prove causation

Nematology in the North Central Region, 1956-1966

There have been many accomplishments in nematology in the North Central Region during the past decade. As a result of the organization of a regional nematology committee, research and teaching in the area have been greatly expanded. New problems of major agricultural significance have been discovered, and some of suspected significance have been revealed. An awareness has developed of a large and important group of animals, many of them plant parasites. Because of sheer numbers alone, nematodes deserve more attention by biologists in all aspects.https://lib.dr.iastate.edu/specialreports/1055/thumbnail.jp

Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with chemotherapy

Although immunotherapy can offer profound clinical benefit for patients with a variety of difficult-to-treat cancers, many tumors either do not respond to upfront treatment with immune checkpoint inhibitors (ICIs) or progressive/recurrent disease occurs after an interval of initial control. Improved response rates have been demonstrated with the addition of ICIs to cytotoxic therapies, leading to approvals from the US Food and Drug Administration and regulatory agencies in other countries for ICI-chemotherapy combinations in a number of solid tumor indications, including breast, head and neck, gastric, and lung cancer. Designing trials for patients with tumors that do not respond or stop responding to treatment with immunotherapy combinations, however, is challenging without uniform definitions of resistance. Previously, the Society for Immunotherapy of Cancer (SITC) published consensus definitions for resistance to single-agent anti-programmed cell death protein 1 (PD-1). To provide guidance for clinical trial design and to support analyses of emerging molecular and cellular data surrounding mechanisms of resistance to ICI-based combinations, SITC convened a follow-up workshop in 2021 to develop consensus definitions for resistance to multiagent ICI combinations. This manuscript reports the consensus clinical definitions for combinations of ICIs and chemotherapies. Definitions for resistance to ICIs in combination with targeted therapies and with other ICIs will be published in companion volumes to this paper

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Rhodium(II)-catalyzed stereocontrolled synthesis of dihydrofuran-3-imines from 1-Tosyl-1,2,3-triazoles

Rhodium(II) acetate catalyzes the denitrogenative transformation of 5-substituted and 4,5-disubstituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ether motifs to oxonium ylides that undergo [2,3]-sigmatropic rearrangement to give substituted dihydrofuran-3-imines in high yield and diastereoselectivity

Small-Scale Extrusion of Corn Masa By-Products

Corn masa by-product streams are high in fiber and are amenable for utilization in livestock feed rations. This approach is a potentially viable alternative to landfilling, the traditional disposal method for these processing residues. Suspended solids were separated from a masa processing waste stream, blended with soybean meal at four levels (0, 10, 20, and 30% wb), and extruded in a laboratory-scale extruder at speeds of 50 rpm (5.24 rad/sec) and 100 rpm (10.47 rad/sec) with temperature profiles of 80-90-100°C and 100-110-120°C. Processing conditions, including dough and die temperatures, drive torque, specific mechanical energy consumption, product and feed material throughput rates, dough apparent viscosity, and dough density, were monitored during extrusion. The resulting products were subjected to physical and nutritional characterization to determine the effects of processing conditions for these blends. Extrudate analysis included moisture content, water activity, crude protein, in vitro protein digestibility, crude fat, ash, product diameter, expansion ratios, unit and true density, color, water absorption and solubility, and durability. All blends were suitable for extrusion at the processing conditions used. Blend ratio had little effect on either processing parameters or extrudate properties; extrusion temperature and screw speed, on the other hand, significantly affected both processing and product properties

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV.IMPORTANCESevere acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and 2003, and infected patients developed an atypical pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) leading to pulmonary fibrosis and death. We identified sets of differentially expressed genes that contribute to ALI and ARDS using lethal and sublethal SARS-CoV infection models. Mathematical prioritization of our gene sets identified the urokinase and extracellular matrix remodeling pathways as the most enriched pathways. By infecting Serpine1-knockout mice, we showed that the urokinase pathway had a significant effect on both lung pathology and overall SARS-CoV pathogenesis. These results demonstrate the effective use of unbiased modeling techniques for identification of high-priority host targets that regulate disease outcomes. Similar transcriptional signatures were noted in 1918 and 2009 H1N1 influenza virus-infected mice, suggesting a common, potentially treatable mechanism in development of virus-induced ALI

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling