Streptomyces as a host for the secretion of heterologous proteins for the production of biopharmaceuticals

The commercial production of therapeutic or diagnostic proteins in recombinant microorganisms is of considerable interest. Several microbial protein production systems have been developed. So far, Escherichia coli have been the commonly employed host. However, proteins expressed in this host remain intracellular and often precipitate as inclusion bodies, which may seriously complicate downstreamprocessing. Faced with this problem, several genera of Gram-positive bacteria are being tested as host for the production of heterologous proteins due to their ability to efficiently secrete proteins in the culture medium. Among them is the genus Streptomyces since several of its species are known to secrete high amounts of proteins. Due to the absence of an extensive restriction-modification system, limited protease activity and the availability of suitable vector systems, Streptomyces lividans is the host of choice for the secretory production of heterologous proteins. The presented results show, that S. lividans can act as an interesting host to produce a number of proteins useful in several disease areas important in the worldwide pharmaceutical sales: i.e. oncology, immunology, cardiovascular diseases and infectious diseases

Shells and humans: molluscs and other coastal resources from the earliest human occupations at the Mesolithic shell midden of El Mazo (Asturias, Northern Spain)

Human populations exploited coastal areas with intensity during the Mesolithic in Atlantic Europe, resulting in the accumulation of large shell middens. Northern Spain is one of the most prolific regions, and especially the so-called Asturian area. Large accumulations of shellfish led some scholars to propose the existence of intensification in the exploitation of coastal resources in the region during the Mesolithic. In this paper, shell remains (molluscs, crustaceans and echinoderms) from stratigraphic units 114 and 115 (dated to the early Mesolithic c. 9 kys cal BP) at El Mazo cave (Asturias, northern Spain) were studied in order to establish resource exploitation patterns and environmental conditions. Species representation showed that limpets, top shells and sea urchins were preferentially exploited. One-millimetre mesh screens were crucial in establishing an accurate minimum number of individuals for sea urchins and to determine their importance in exploitation patterns. Environmental conditions deduced from shell assemblages indicated that temperate conditions prevailed at the time of the occupation and the morphology of the coastline was similar to today (rocky exposed shores). Information recovered relating to species representation, collection areas and shell biometry reflected some evidence of intensification (reduced shell size, collection in lower areas of exposed shores, no size selection in some units and species) in the exploitation of coastal resources through time. However, the results suggested the existence of changes in collection strategies and resource management, and periods of intense shell collection may have alternated with times of shell stock recovery throughout the Mesolithic.This research was performed as part of the project “The human response to the global climatic change in a littoral zone: the case of the transition to the Holocene in the Cantabrian coast (10,000–5000 cal BC) (HAR2010-22115-C02-01)” funded by the Spanish Ministry of Economy and Competitiveness. AGE was funded by the University of Cantabria through a predoctoral grant and IGZ was funded by the Spanish Ministry of Economy and Competitiveness through a Juan de la Cierva grant. We also would like to thank the University of Cantabria and the IIIPC for providing support, David Cuenca-Solana, Alejandro García Moreno and Lucia Agudo Pérez for their help. We also thank Jennifer Jones for correcting the English. Comments from two anonymous reviewers helped to improve the paper

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations. METHODS: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Stanaway JD, Afshin A, Gakidou E, et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1923-1994.Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd

Torque máximo en jugadores profesionales de fútbol asociación durante la pretemporada, Toluca, México, 2010

La dinamometría isocinética es la técnica que estudia la fuerza muscular ejercida dinámicamente, en un rango de movimiento determinado y a una velocidad constante y programable. En la actualidad los avances tecnológicos nos han permitido obtener aparatos más sofisticados y de mayor precisión, los dinamómetros modernos, nos dan la posibilidad de objetivar, en una gráfica, las curvas de fuerza/arco de movimiento y relacionar los diferentes valores obtenidos, entre sí y con los de otras exploraciones; por ello, es un instrumento preciso para la evaluación de la función muscular y valoración articular. La medida de la fuerza muscular es una forma de evaluar la efectividad de los programas de entrenamiento y rehabilitación siendo la dinamometría isocinética un buen método para ello.Introducción: La dinamometría isocinética es la técnica que estudia la fuerza muscular ejercida dinámicamente, en un rango de movimiento determinado y a una velocidad constante y programable. La medida de la fuerza muscular es una forma de evaluar la efectividad de los programas de entrenamiento y rehabilitación siendo la dinamometría isocinética un buen método para ello. Objetivo: Determinar el pico de torque máximo en jugadores profesionales de acuerdo a su posición dentro del terreno de juego, así como identificar los déficits y desequilibrio de fuerza, en futbolistas profesionales. Materiales y métodos: Previo calentamiento, se colocó a los futbolistas en el equipo Con-trex con un ángulo articular constante de la cadera de 100 grados, se inició la evaluación con la extremidad dominante y se midió el pico torque concéntrico del cuádriceps e isquitobiliales con una velocidad angular de 120 grados. Se hicieron 3 sesiones en 8, 6 y 5 repeticiones, con 1 minuto de recuperación. El procedimiento inició con extensión y finalizó con flexión. Resultados: Se evaluaron 43 jugadores de futbol asociación, hombres de 23- 26 años de edad, 13 defensas, que obtuvieron 156.8 Nm promedio en flexión derecha y 152.1 Nm en flexión izquierda, los medios el grupo más numeroso con 21 jugadores, tuvieron un promedio de 144.1 Nm en flexión derecha y 140.5 Nm en flexión izquierda. Los delanteros, 9 en total tuvieron una media de 155.4 Nm en flexión derecha y 151.4 Nm en flexión izquierda

Estudio morfológico inmunocitoquímico y ultraestructural de las neuronas de la corteza cerebral en ratones afectados por rabia

IP 2104-04-11805interneuronas en la corteza cerebral del raton / O. Torres...[etal.]. --En: Biomedica. - Vol. 22, no. 1 (jul;2002); p. 118. - ISSN 01204157. - IV encuentro nacional deinvestigacion de enfermedades infecciosos / Orlando;Torres Fernandez. -- En: Infectio: revista de la asociacion colombiana deinfectologia. -- Vol. 8. No. 2 ( jun;2004); p.57-71. -- ISSN 01239392. -- Colocacion inmunocitoquimica y ultraestructural del virus de la rabia en;Orlando Torres Fernandez...[et al.]. -- En Revista de la asociacion colombiana de Ciencias Biologicas. -- Vol.;16, no. 2 (jul-dic); p. 140. -- ISSN 01204173. -- Distribucionde la expresion de tres proteinas marcadoras de;neuronas de la corteza cerebral que expresan proteinas ligadorasde calcio(CaBP) / Torres Fernandez Orlando.;'-- en: Infectio : Revista de La asociacion colombiana de Infectologia. --Vol. 8, no. 2 (jun 2004); p. 115. --;ISSN 01239392. -- Efecto diferencial de la infeccion con virusfijo y virus calle de la rabia sobre la;expresion de calbindina (CB) en diferentes areas del cerebro deratones /Torres Fernandes O. -- En: Infectio;: revista de la asociacion colombiana de infectologia . --Vol.8, no. 2 (jun 2004); p. 115. -- ISSN 01239392.;'-- PONENCIA(S) en Congreso: Utilidad de las proteinas ligadorasde calcio(parvoalbumina, calbindina y;calretinina) como marcadores neuronales y su aplicacion eninvestigacion neuropatologica / Orlando Torres;Fernandez...[et al.]. -- En: Simposio colombiano de neurociencias (2: 2003jun. 12-14 : Colombia, Bogot{lcub}a). --;Bogotá : Pontificia Universidad Javeriana, 2003. - 28 cm.;International Journal of Neuroscience. -- Vol. 115, no. 10(205). -- Patologia dentritica en la corteza;frontal de ratones inoculados con rabia / Orlando Torres Fernandez...[et al.]. -- En: Revista de la asociacion;colombiana de Ciencias Biologicas. -- Vol. 16, no. 2. (jul'-dic);p. 161. -- ISSN 0120-4173. . -- La infeccion;ARTICULO(S) EN REVISTA: Efecto de la infeccion por el virus dela rabia sobre la expresion de parvoalbumina,;calbindina y calretinina en la corteza cerebral de ratones/ Orlando Torres Fernandez... [et al.]. -- En:;Biomedica. -- Vol. 24, no. 1 (2004); p. 63-78. -- ISSN 0120-4157. -- Calbindin distribution in cortical and;subcortical brain structures of normal and rabies infectedmice/ O. Torres Fernandez... [et al.]. -- En:;por el virus de la rabia induce aumento de la expresion deparvoalbumina en la corteza cerebral de ratones

Evaluación prospectiva del desarrollo de nefropatía inducida por contraste en pacientes con síndrome coronario agudo tratados con angiografía coronaria rotacional vs. angiografía coronaria convencional: Estudio CINERAMA

Introducción y objetivos: La angiografía coronaria rotacional (ACR) permite reducir la cantidad de contraste administrado y puede prevenir el desarrollo de nefropatía inducida por contraste (NIC) durante los procedimientos coronarios invasivos. El objetivo del estudio es evaluar el impacto de la ACR en la aparición de NIC (aumento de creatinina ≥0,5 mg/dL o ≥25%) tras un síndrome coronario agudo. Métodos: De abril a septiembre de 2016 se seleccionaron prospectivamente pacientes con síndrome coronario agudo remitidos para coronariografía diagnóstica con posibilidad de angioplastia ad hoc, que fueron estudiados con ACR o angiografía coronaria convencional (ACC) según criterio del operador. Se compararon la NIC (variable de valoración primaria), variables analíticas, angiográficas y clínicas. Resultados: De 235 pacientes reclutados, 116 pacientes fueron estudiados con ACR y 119 pacientes con ACC. El grupo de ACR presentaba mayor edad (64,0 ± 11,8 vs. 59,7 ± 12,1 años; p = 0,006), más mujeres (44,8 vs. 17,6%; p < 0,001) y peor filtrado glomerular estimado (76 ± 25 vs. 86 ± 27 mL/min/1,73 m2; p = 0,001), con menos angioplastias (p < 0,001). Asimismo, el grupo de ACR recibió menos contraste (113 ± 92 vs. 169 ± 103 mL; p < 0,001), diferencias que se mantuvieron en los procedimientos diagnósticos (54 ± 24 vs. 85 ± 56 mL; p < 0,001) y diagnóstico-terapéuticos (174 ± 64 vs. 205 ± 98 mL; p = 0,049). El grupo de ACR presentó menos NIC (4,3 vs. 22,7%; p < 0,001): en el análisis de regresión se objetivó que continuaba relacionándose con menor desarrollo de NIC (riesgo relativo ajustado: 0,868; IC 95%: 0,794-0,949; p = 0,002). No hubo diferencias en las variables clínicas. Conclusiones: La ACR se asoció con menor administración de contraste durante procedimientos coronarios invasivos tras un síndrome coronario agudo, lo que resultó en una menor aparición de NIC