Impact of \u3ci\u3eHaemophilus influenzae\u3c/i\u3e type b conjugate vaccine on bacterial meningitis in the Dominican Republic

OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib) vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among children \u3c 5 years of age were identified from admission records of the main pediatric hospital in Santo Domingo during 1998-2004. Laboratory criteria were used to classify meningitis cases with probable bacterial etiology; confirmed cases had positive bacterial culture or antigen detection in cerebrospinal fluid. Cumulative incidence rates of confirmed and probable bacterial meningitis were calculated for children living in the National District. Confirmed cases of Hib meningitis were enrolled in a case-control study with age- and neighborhood-matched control children to calculate vaccine effectiveness. RESULTS: Before vaccine introduction, annual rates of meningitis with probable bacterial etiology were 49 cases per 100 000 children \u3c 5 years old; Hib accounted for 60% of confirmed bacterial cases. During 2002-2004, after vaccine introduction, annual rates of probable bacterial meningitis were 65% lower at 16 cases per 100 000, and Hib accounted for 26% of confirmed cases. Rates of Hib meningitis and probable bacterial meningitis with no determined etiology declined by 13 and 17 cases per 100 000, respectively. CONCLUSIONS: Introduction of Hib vaccine substantially reduced the incidence of confirmed and probable bacterial meningitis in the Dominican Republic. The estimated impact of Hib vaccination was twice as great when non-culture-confirmed disease was included

Mineralization of human premolar occlusal fissures: a quantitative histochemical microanalysis

The mechanisms of cariogenesis in occlusal fissures remain elusive because of limited information about fissure structure and wall mineralization. The purpose of the present study was to determine the correlation between morphological patterns in occlusal fissures in human premolars and quantitative histochemical patterns of mineralization in the walls of these formations. We used scanning electron microscopy and quantitative X-ray microanalysis with the peak-tolocal background ratio method and microcrystalline calcium salts as standards. We distinguished three morphological patterns of fissures in scanning electron microscopic images. The wall of the fissures was less mineralized than the control enamel in all three types of fissures. Because the fissure walls are hypomineralized, we suggest that practicing dentists should take into account the degree of mineralization when they are preparing the fissures for the application of sealant.This work was partially supported by the Ministerio de Educación y Cultura (PB97-0840) and the Agencia Española de Cooperación Internacional (AECI)

Inhibition of NAE-dependent protein hyper-NEDDylation in cystic cholangiocytes halts cystogenesis in experimental models of polycystic liver disease

Background Polycystic liver diseases (PLDs) are genetic inherited disorders characterized by the progressive growth of numerous intrahepatic biliary cysts, which are the main cause of morbidity. Previous studies revealed that cystic cholangiocytes are characterized by endoplasmic reticulum stress and aberrant posttranslational modification (PTM) of proteins, in particular hyper-SUMOylation, that promote PLD pathobiology. Protein NEDDylation is a newly characterized PTM that modulates a plethora of biological processes and its dysregulation is associated with the development and progression of several human diseases. However, the role of NEDDylation in PLD remains elusive. Objective To explore the role of protein NEDDylation in PLD and its potential therapeutic regulatory value. Methods Levels and functional effects of NEDDylation, including response to Pevonedistat (first-in-class selective inhibitor of the NEDDylation E1 enzyme NAE), were assessed in vitro, in vivo, and/or in patients with PLD. NEDDylated protein levels in normal and cystic human cholangiocytes were assessed by immunoprecipitation, and the proteomic profile was further analyzed by mass spectrometry. Results and Conclusion The genes involved in the NEDDylation pathway were found overexpressed (mRNA) in polycystic human and rat liver tissue, as well as in cystic cholangiocytes in culture, compared to controls. Elevated levels of NEDDylated proteins were further confirmed in cystic cholangiocytes in vitro, which diminished under Pevonedistat incubation. Pevonedistat promoted apoptotic cell death and reduced proliferation in cystic cholangiocytes in vitro. Comparative proteomic profiling of NEDD8-immunoprecipitated proteins between normal and cystic cholangiocytes in culture reported candidate proteins involved in cystogenesis, mostly associated with protein biogenesis and quality control. All these data indicate that cystic cholangiocytes display increased protein NEDDylation, contributing to cell survival and proliferation, ultimately supporting hepatic cystogenesis. Targeting of protein hyper-NEDDylation in cystic cholangiocytes inhibits cystogenesis in experimental models, representing a novel therapeutic opportunity in PLD.Spanish Carlos III Health Institute (ISCIII), Grant/Award Numbers: CON14/00129, CPII19/00008, FIS PI12/00380, FIS PI14/ 00399, FIS PI15/01132, FIS PI17/00022, FIS PI18/01075, FIS PI20/00186, Sara Borrell CD19/00254; Diputacion Foral de Gipuzkoa, Grant/Award Numbers: DFG15/010, DFG16/004; Department of Health of the Basque Country, Grant/Award Numbers: 2015111100, 2017111010, 2019111024; Euskadi RIS3, Grant/Award Numbers: 2016222001, 2017222014, 2018222029, 2019222054, 2020333010; Department of Industry of the Basque Country, Grant/Award Number: KK-2020/00008; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: RYC-2015-17755; Ministerio de Ciencia, Innovacion y Universidades, Grant/ Award Number: SAF2017-87301-R; Ayudas para apoyar grupos de investigacion del Sistema Universitario Vasco, Grant/Award Number: IT971-16; Universita Politecnica delle Marche, Grant/Award Number: PSA2017_UNIVPM; European Association for the Study of the Liver, Grant/Award Number: Sheila Sherlock Award 2017; Spanish Ministry of Science and Innovation, Grant/Award Number: BES-2014-069148; Basque Government, Grant/Award Number: PRE_2016_1_0269; Basque Foundation for Innovation and Health Research, Grant/Award Number: BIO15/CA/016/BD; Fundacion Cientifica de la Asociacion Espanola Contra el Cancer; La Caixa Scientific Foundation, Grant/ Award Number: HR17-00601; CIBERehd; Fondo Europeo de Desarrollo Regional Documen

Efectividad biológica de organofosforados y carbamatos en el control de nematodos en banano

En México el banano es el segundo frutal de mayor importancia económica, con una producción de 2.2 millones de toneladas anuales; los nematodos son las plagas más importantes del banano afectando el crecimiento y desarrollo debido al daño ocasionado en raíces y rizoma, los más reportados han sido: Radopholus similis (nematodo barrenador), Helicotylenchus multicinctus (nematodo del espiral) y Meloidogyne spp. (nematodo agallador). El principal método de control se ha basado en productos químicos  con  resultados  muy  variados.  En  este  estudio  se  evaluaron  la  eficacia  biológica  de nematicidas organofosforados y carbamatos para el control de estas tres especies mediante las variables densidad de nematodos en suelo cercano a raíz y en raíz, porcentaje de daño causado (severidad), peso de raíces muertas, peso de raíces sanas y vigor de hijuelos mediante el diámetro basal, altura y número de hojas. De acuerdo con los resultados obtenidos, el producto organoclorado (Terbufos) tuvo una eficacia por debajo del 80% a diferencia del carbamato (Oxamil) Oaxamil que en sus dosis de 2.7 ml/hijo mostró tener mayor eficacia en las especies de Radhopolus similis y Pratylenchus sp. en raíz, en tanto que para el control de Meloidogyne sp. fue mejor la dosis de 2.4 ml/hijo. Para el control de nematodos en suelo cerca de la raíz Oaxamil en dosis de 2.4 ml/hijo obtuvo mejor resultado para el control de Radhopolus similis y Meloidogyne sp. en tanto que para el control de Pratylenchus sp. fue mejor en su dosis de 2.7 ml/hijo

New Structured Materials in the Study of the Mechanobiological Processes Related to the Heart Failure

Cardiovascular diseases are the number one of death globally. According to the World Health organization 17.7 million people died from cardiovascular diseases in 2015, representing 31% of all global deaths.  In these diseases the cardiac homeostasis is disrupted by a non-appropriate myocardium remodelling. The cardiac extracellular matrix (ECM) provides not only the biochemical environment but also a natural scaffold surrounding and connecting cardiac cells and distributing mechanical forces throughout the organ. Thus, the properties of the ECM are essential for the maintenance of the functional myocardium. Alterations in cardiac ECM structure associated with heart failure influence cell-matrix and cell-cell adhesions modifying cell shape and mechanotransduction.The need to understand the cardiac ECM remodelling mechanisms that allow us to identify new therapeutic targets lead us to create biomimetic scaffolds which emulate the structure, topography, mechanics and chemical composition of ECM.Here, we present the development of modulable materials for the manufacturing, by using photopolymerizable materials, of structured hydrogels with myocardium properties of stiffness and elastic modulus in physiological and pathological conditions

Efectividad biológica de carbamatos para el control de (Meloidogyne sp.) en tomate y zanahoria en Morelos

El jitomate y la zanahoria son dos hortalizas muy susceptibles a nematodos agalladores como Meloidogyne spp. En zanahoria ocasionan serias reducciones en los rendimientos y pueden incluso llegar a la pérdida total del cultivo, cuando se presenta en zanahoria hay una deformación de las raíces adventicias y por tanto una deformación en la raíz principal, esto hace que se pierda la presentación y calidad de fruto. En tomate el comportamiento es similar, con la formación de agallas en las raíces impidiendo una buen absorción de agua y nutrientes. En este experimento se evaluaron dos productos del grupo químico de los carbamatos, más utilizados para el control de nematodo agallador para visualizar posibles efectos de resistencia a este grupo químico. Los resultados en zanahoria muestran que carbofuran en dosis de 2500 g. ha-1 es quien mejor eficacia tiene para el control de Meloidogyne, mientras que la dosis baja es la que menos control tiene. En el caso del tomate el Oaxamil en su dosis de 4.7 L.ha-1 es la que mejor controla la población de nematodos agalladores y por lo tanto aumenta el rendimiento en la producción

New Structured Materials in the Study of the Mechanobiological Processes Related to the Heart Failure

Cardiovascular diseases are the number one of death globally. According to the World Health organization 17.7 million people died from cardiovascular diseases in 2015, representing 31% of all global deaths. In these diseases the cardiac homeostasis is disrupted by a non-appropriate myocardium remodelling. The cardiac extracellular matrix (ECM) provides not only the biochemical environment but also a natural scaffold surrounding and connecting cardiac cells and distributing mechanical forces throughout the organ. Thus, the properties of the ECM are essential for the maintenance of the functional myocardium. Alterations in cardiac ECM structure associated with heart failure influence cell-matrix and cell-cell adhesions modifying cell shape and mechanotransduction. The need to understand the cardiac ECM remodelling mechanisms that allow us to identify new therapeutic targets lead us to create biomimetic scaffolds which emulate the structure, topography, mechanics and chemical composition of ECM. Here, we present the development of modulable materials for the manufacturing, by using photopolymerizable materials, of structured hydrogels with myocardium properties of stiffness and elastic modulus in physiological and pathological conditions

Targeting UBC9-Mediated Protein Hyper-SUMOylation in Cystic Cholangiocytes Halts Polycystic Liver Disease in Experimental Models

BACKGROUND & AIMS: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of multiple fluid-filled biliary cysts. Most PLD-causative genes participate in protein biogenesis and/or transport. Post-translational modifications (PTMs) are implicated in protein stability, localization and activity, contributing to human pathobiology; however, their role in PLD is unknown. Herein, we aimed to unveil the role of protein SUMOylation in PLD and its potential therapeutic targeting. METHODS: Levels and functional effects of SUMOylation, along with response to S-adenosylmethionine (SAMe, inhibitor of the SUMOylation enzyme UBC9) and/or short-hairpin RNAs (shRNAs) against UBE2I (UBC9), were evaluated invitro, invivo and/or in patients with PLD. SUMOylated proteins were determined by immunoprecipitation and proteomic analyses by mass spectrometry. RESULTS: Most SUMOylation-related genes were found overexpressed (mRNA) in polycystic human and rat liver tissue, as well as in cystic cholangiocytes in culture compared to controls. Increased SUMOylated protein levels were also observed in cystic human cholangiocytes in culture, which decreased after SAMe administration. Chronic treatment of polycystic (PCK: Pkdh1-mut) rats with SAMe halted hepatic cystogenesis and fibrosis, and reduced liver/body weight ratio and liver volume. Invitro, both SAMe and shRNA-mediated UBE2I knockdown increased apoptosis and reduced cell proliferation of cystic cholangiocytes. High-throughput proteomic analysis of SUMO1-immunoprecipitated proteins in cystic cholangiocytes identified candidates involved in protein biogenesis, ciliogenesis and proteasome degradation. Accordingly, SAMe hampered proteasome hyperactivity in cystic cholangiocytes, leading to activation of the unfolded protein response and stress-related apoptosis. CONCLUSIONS: Cystic cholangiocytes exhibit increased SUMOylation of proteins involved in cell survival and proliferation, thus promoting hepatic cystogenesis. Inhibition of protein SUMOylation with SAMe halts PLD, representing a novel therapeutic strategy. LAY SUMMARY: Protein SUMOylation is a dynamic post-translational event implicated in numerous cellular processes. This study revealed dysregulated protein SUMOylation in polycystic liver disease, which promotes hepatic cystogenesis. Administration of S-adenosylmethionine (SAMe), a natural UBC9-dependent SUMOylation inhibitor, halted polycystic liver disease in experimental models, thus representing a potential therapeutic agent for patients.Spanish Carlos III Health Institute (ISCIII) [J.M. Banales (FIS PI12/00380, PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008); M.J. Perugorria (FIS PI14/00399, PI17/00022 and PI20/00186); P.M. Rodrigues (Sara Borrell CD19/00254)] cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); Ministerio de Ciencia, Innovación y Universidades (MICINN; M.L. Martinez-Chantar: SAF2017-87301-R); “Instituto de Salud Carlos III” [CIBERehd: J.M. Banales, M.J. Perugorria, M.L. Martinez-Chantar and L. Bujanda], Spain; “Diputación Foral Gipuzkoa” (J.M. Banales: DFG15/010, DFG16/004), Department of Health of the Basque Country (M.J. Perugorria: 2019111024, 2015111100 and J.M. Banales: 2017111010), “Euskadi RIS3” (J.M. Banales: 2016222001, 2017222014, 2018222029, 2019222054, 2020333010), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J.M. Banales and M.L. Martinez-Chantar) and Department of Industry of the Basque Country (J.M. Banales: Elkartek: KK-2020/00008). La Caixa Scientific Foundation (J.M. Banales and M.L. Martinez-Chantar: HR17-00601). “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to J.M. Banales and M.L. Martinez-Chantar). “Ayudas para apoyar grupos de investigación del Sistema Universitario Vasco” (IT971-16 to P.A.). Università Politecnica delle Marche PSA2017_UNIVPM grant (to M. Marzioni). National Institutes of Health (NIH) of United States of America (DK24031 to N.F. LaRusso). MJ Perugorria was funded by the Spanish Ministry of Economy and Competitiveness (MINECO: “Ramón y Cajal” Program RYC-2015-17755), P.Y. Lee-Law by the European Association for the Study of the Liver (EASL; Sheila Sherlock Award 2017), F.J. Caballero-Camino by the Spanish Ministry of Science and Innovation (BES-2014-069148), and P. Olaizola and A. Santos-Laso by the Basque Government (PRE_2016_1_0269, PRE_2015_1_0126). We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). The funding sources had no involvement in study design, data collection and analysis, decision to publish, or preparation of the article

Engineering of III-Nitride Semiconductors on Low Temperature Co-fired Ceramics

This work presents results in the feld of advanced substrate solutions in order to achieve high crystalline quality group-III nitrides based heterostructures for high frequency and power devices or for sensor applications. With that objective, Low Temperature Co-fred Ceramics has been used, as a noncrystalline substrate. Structures like these have never been developed before, and for economic reasons will represent a groundbreaking material in these felds of Electronic. In this sense, the report presents the characterization through various techniques of three series of specimens where GaN was deposited on this ceramic composite, using diferent bufer layers, and a singular metal-organic chemical vapor deposition related technique for low temperature deposition. Other single crystalline ceramic-based templates were also utilized as substrate materials, for comparison purposes