Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior

Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons. In this study, we developed an adenovirus expressing GK shRNA to inhibit GK expression in vivo. When injected into the 3V of rats, this adenovirus preferentially transduced tanycytes. qRT-PCR and Western blot assays confirmed GK mRNA and protein levels were lower in GK knockdown animals compared to the controls. In response to an intracerebroventricular glucose injection, the mRNA levels of anorexigenic POMC and CART and orexigenic AgRP and NPY neuropeptides were altered in GK knockdown animals. Similarly, food intake, meal duration, frequency of eating events and the cumulative eating time were increased, whereas the intervals between meals were decreased in GK knockdown rats, suggesting a decrease in satiety. Thus, GK expression in the ventricular cells appears to play an important role in feeding behavior.Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad de Concepción; ChileFil: Millán, Carola. Universidad de Concepción; Chile. Universidad Adolfo Ibañez; ChileFil: Barahona, María José. Universidad de Concepción; ChileFil: Recabal, Antonia. Universidad de Concepción; ChileFil: Salgado, Magdiel. Universidad de Concepción; ChileFil: Martinez, Fernando. Universidad de Concepción; ChileFil: Ordenes, Patricio. Universidad de Concepción; ChileFil: Elizondo Vega, Roberto. Universidad de Concepción; ChileFil: Sepúlveda, Fernando. Universidad de Concepción; ChileFil: Uribe, Elena. Universidad de Concepción; ChileFil: García Robles, María de los Ángeles. Universidad de Concepción; Chil

Mechanisms of Pituitary Tumorigenesis. Study of Angiogenic and Proliferation factors

Introduction and objectives: Angiogenesis is an essential process in tumor development. Nevertheless, discrepancies in the angiogenic pattern of pituitary tumors, in terms of hormonal phenotype, size or invasiveness have been found. Our aim was to study the expression of VEGF and FGF2 growth factors, and their importance in the vascularization of pituitary adenomas. We also quantified blood vessels with the endothelial cell markers CD31 and CD34 determining the vascular area, and the proliferation rate through PCNA and Ki67 index. Materials and Methods: We studied 76 pituitary macroadenomas that were surgically resected in the period between 2006 and 2010 from a total of 276 patients with this pathology. Adenomas were classified into prolactinomas (PRL), somatotropinomas (GH), corticotropinomas (ACTH), non-functioning (NF) and plurihormonal (Ph) according to their hormonal secretion. Samples were collected in formalin, embedded in paraffin, and immunohistochemistry was performed from histological sections for endothelial markers CD31 and CD34; and for Ki-67 to study cell proliferation. VEGF, CD31 and PCNA were measured by Western blot. We compared results with normal glands (N=6). Results: VEGF expression levels, found in all of the samples analyzed, were higher in resistant prolactinomas than in other pituitary adenomas. This protein was detected in endothelial cells of blood vessels and in tumor cells cytoplasms and nuclei. Fifty-six percent of samples were positive for FGF2, the other potent angiogenic factor studied, showing cytoplasmatic and extracellular matrix localization. We obtained a strong positive correlation between VEGF and CD31 in tumor samples, but we did not find lineal correlation between PCNA and VEGF, or between Ki-67 and VEGF in the samples studied. The vascular area was higher in normal tissues than in tumors when CD34 was used as endothelial cell marker. Conclussion: The importance of studying angiogenesis in pituitary adenomas lies in the need to find molecular markers that can predict tumor behavior. We could demonstrate the expression of VEGF and FGF2, two potent angiogenic factors, and the existence of linear correlation between VEGF and CD31. Our results are indicative of the existence of angiogenesis in pituitary adenomas; therefore the blockage of angiogenesis might be proposed as an alternative strategy for cases of resistance to standard therapy.Fil: Berner, Silvia Inés. Hospital Santa Lucía; Argentina. Clínica Santa Isabel; ArgentinaFil: de Bonis, Cristian. Clínica Santa Isabel; ArgentinaFil: Martinez, Diego. Hospital Santa Lucía; Argentina. Clínica Santa Isabel; ArgentinaFil: Demarchi, Gianina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; ArgentinaFil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Cristina, Silvia Carolina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; Argentin

Cross-cultural adaptation and psychometric evaluation of the early childhood oral health impact scale (ECOHIS) in chilean population

The Early Childhood Oral Health Impact Scale (ECOHIS) measures the impact of dental diseases on Oral Health-Related Quality of Life both in children and their families. The aim of this study was to develop a Chilean Spanish version of the ECOHIS that is conceptually equivalent to the original and to assess its acceptability, reliability and validity in the preschool population of Chile. The Chilean version of the ECOHIS was obtained through a process including forward and back-translation, expert panel, and cognitive debriefing interviews. To assess metric properties, a cross-sectional study was carried out in Carahue, Southern Chile (April-October 2016). Children younger than six years old without systemic diseases, disabilities or chronic medication from eleven public preschools were included. Parents were invited to complete the Chilean version of the ECOHIS, PedsQL™4.0 Generic Core and PedsQL Oral Health scales, and to answer global questions about their children's general and oral health. A subsample was administrated ECOHIS a second time 14-21 days after. A clinical examination was performed to assess dental caries, malocclusion, and traumatic dental injuries. Reliability was evaluated using measures of internal consistency (Cronbach's alpha) and reproducibility (Intraclass correlation coefficient - ICC). Construct validity was assessed by testing hypotheses based on available evidence about known groups and relationships between different instruments. The content comparison of the back-translation with the original ECOHIS showed that all items except one were conceptually and linguistically equivalent. The cognitive debriefing showed a suitable understanding of the Chilean version by the parents. In the total sample (n = 302), the ECOHIS total score median was 1 (IQR 6), floor effect was 41.6%, and ceiling effect 0%. Cronbach's alpha was 0.89 and the ICC was 0.84. The correlation between ECOHIS and PedsQL™4.0 Generic Core was weak (r = 0.21), while it was strong-moderate (r = 0.64) with the PedsQL Oral Health scale. In the known groups comparison, the ECOHIS total score was statistically higher in children with poor than excellent/very good oral health (median 11.6 vs 0, p < 0.01), and in the high severity than in the caries-free group (median 8 vs 0.5, p < 0.01). No differences were found according to malocclusion and traumatic dental injuries groups. These results supported the feasibility, reliability and validity of the Chilean version of ECOHIS questionnaire for preschool children through proxy

Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease

T. Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged &lt;18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value &lt; 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.This work was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2), The study was cofunded by ERDF Funds (FEDER) from the European Commission, “A way of making Europe

A crowdsourcing database for the copy-number variation of the Spanish population

Background: Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results: Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion: SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Manejo de las crisis convulsivas en la clínica veterinaria de urgencias.

Las crisis convulsivas son uno de los motivos más frecuentes en la clínica de urgencias. Las convulsiones se deben a una disfunción prosencefálica pudiendo ser varias las causas de estas. A su vez, deben ser diferenciadas de otras entidades como trastornos paroxísticos del movimiento o síncopes entre otros, lo cual no siempre es tarea fácil. Existen dos situaciones que pueden poner en peligro la vida del paciente y que necesitan tratarse lo antes posible con el fin de disminuir las consecuencias neurológicas y sistémicas derivadas de ellos. Se trata de las convulsiones en racimo (o en clúster) y, sobre todo, del estado epiléptico. De este modo, es fundamental seguir un protocolo de actuación cuyos objetivos son los de detener la actividad convulsiva, tratar las alteraciones sistémicas y descubrir las posibles causas subyacentes. El pronóstico dependerá de la causa que está provocando los ataques.Si después de realizar todas las pruebas diagnósticas pertinentes no se conoce la causa que ha producido esta crisis, empezaremos a tratarlo como una crisis epiléptica idiopática con posible origen genético. El principal problema en el diagnóstico es la limitación existente en las pruebas diagnósticas, las cuales no están al alcance de todo el mundo o no se utilizan de forma rutinaria en la clínica (como es el caso del electroencefalograma). Por todo lo dicho, el objetivo de este trabajo es el de realizar una revisión bibliográfica y aplicarla a un caso clínico.<br /

Computer vision for automatic detection of crop heights

[Resumen] En este trabajo se presenta la combinación de visión estéreo y un algoritmo basado en kernels para la identificación automática de la altura de un cultivo. La técnica desarrollada alivia la necesidad de realizar controles periódicos del cultivo en persona, reduciendo costes tanto por disminuir el tiempo del personal como por identificar rápidamente retrasos en el crecimiento del cultivo. La propuesta utiliza operaciones morfológicas y la transformada de Hough para el trazo de las rectas que delimitan la parte superior e inferior de la banda de la planta. El algoritmo es de bajo coste computacional, permitiendo su aplicación en dispositivos IoT con microprocesadores empotrados. Los resultados se aplican sobre imágenes reales, obteniendo un error en la estimación de altura del 3 %.[Abstract] This article introduces a new algorithm based on stereoscopic imaging and kernels for the automatic and intelligent detection of crop heights. The kernel-based algorithm alleviates the need for humans in the loop cutting costs by prioritizing personnel time and quickly identifying stunted growth due to stress. The kernels algorithm consists of morphological operations and the Hough transform to identify the bottom and top of a specific crop by varying kernel sizes. The algorithm is computationally low cost allowing for IoT based application and produces as little as 3% error.Junta de Andalucía; IRRIGATE-PY20 RE 017 LOYOL