Role of Haptoglobin in Polycystic Ovary Syndrome (PCOS), Obesity and Disorders of Glucose Tolerance in Premenopausal Women

alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance.<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes. alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients

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

Plan de gestión integral de residuos sólidos PGIRS municipio de Anapoima Cundinamarca

El manejo de los residuos sólidos en Colombia, ha sido un tema crítico para el Gobierno Nacional que ha desarrollado infructuosos esfuerzos por normalizar este sector, aun sin obtener resultados concretos, de hecho los esfuerzos propuestos por mejorar la calidad de la vida urbana, propuestos en el Plan de Desarrollo 1998-2002 durante el gobierno Pastrana, involucraban la exigencia a los entes territoriales de definir alternativas para el manejo de los residuos sólidos, situación que se planteo en el decreto 1713 de 2002. Es así como en su artículo 8° estableció que a partir de la vigencia del decreto, los Municipios y Distritos, deberían elaborar y mantener actualizado un Plan Municipal o Distrital para la Gestión Integral de Residuos o desechos sólidos en el ámbito local y/o regional según fuera el caso, enmarcado en la política para la Gestión Integral de los Residuos expedida por el Ministerio del Medio Ambiente. Sin embargo lo anterior no se logró, tal como lo manifiesta el plan de Desarrollo hacia un camino de propietarios, del Gobierno del Presidente Álvaro Uribe en su primer periodo, en el cual al realizar el diagnóstico del sector, se reconoce que “aproximadamente 27.500 toneladas diarias de residuos sólidos se generan diariamente en Colombia. El 75% de los municipios tienen con disposición final inadecuada de residuos sólidos”, este hecho es ampliado al mencionar que : “En la disposición final de residuos sólidos, de una muestra de 1.086 municipios se han identificado 565 botaderos a cielo abierto, 350 municipios que expresan disponer relleno sanitario, de los cuales más de la mitad son botaderos con alguna técnica inadecuada de manejo; 32 municipios hacen disposición en cuerpos de agua, 5 utilizan complementariamente incineración y 44 realizan alguna actividad de aprovechamiento. En términos generales, el 75% de los municipios del país están efectuando una disposición final inadecuada. No obstante, las soluciones de disposición final de residuos sólidos han sido de corto plazo, y frecuentemente se han presentado emergencias sanitarias y ambientales que han generado impacto temporal en ciudades capitales como Bogotá, Medellín, Cali, Ibagué, Cartagena y Barranquilla”. Ante esta situación, el gobierno Nacional, en el nuevo plan sectorial, se propone apoyar entonces a las entidades territoriales en el desarrollo de Planes de Gestión Integral de Residuos Sólidos - PGIRS reglamentados por el Decreto 1713 de 2002, y culminar el desarrollo e implementación del sistema de información del sector, situación que aún hoy está siendo perfeccionada, pues todavía no se han dado soluciones concretas al tema. De acuerdo con la definición plasmada en el Decreto 1713 de 2002, la “Gestión integral de residuos sólidos el Sistema Integral para la Gestión de los Residuos Sólidos, propuesto para el municipio de Anapoima consiste entre otras a la construcción de una planta, que corresponde a una estrategia de la valorización de las basuras, cuyo objetivo es la prestación eficaz del Servicio de Aseo, esto significa que se entiende como una alternativa que involucra el manejo de una tecnología apropiada a las condiciones locales (el sistema contempla el manejo de tecnologías de bajo costo que involucran reciclaje manual y mecánico empleando equipos de fabricación nacional y la biodegradación anaeróbica de residuos en el caso de los orgánicos, comprobadas en diversos procesos a una menor escala que la municipal, operaciones privadas en el país, pero que poco a poco han consolidado su efectividad en los sitios en que han sido implementadas), frecuencias y horarios de recolección y barrido establecidos, dando la mejor utilización social y económica a los recursos administrativos, técnicos y financieros disponibles en beneficio de los usuarios de tal forma que se garantice la salud pública y la preservación del medio ambiente. Posteriormente el Decreto 1505 del 2003, estableció un nuevo plazo máximo de 2 años, para la elaboración e iniciación de la ejecución del Plan, contado a partir de la fecha de publicación de la metodología que para el efecto expidiera el Ministerio de Ambiente, Vivienda y Desarrollo Territorial. La metodología referenciada fue expedida en la Resolución 1045 el día 26 de Septiembre de 2003. Acorde con los términos establecidos por la Resoluciones 1045 de 2003 y ajustados por la Resolución 477 de 2004, para poblaciones menores de 50.000 habitantes, el plazo vencía el 26 de Septiembre de 2005. Las autoridades competentes decidieron efectuar algunos ajustes al PGIRS cuando se tuvieran recursos para hacerlo, quedando mientras tanto la formulación como se entregó el plan inicial mencionado. El presente trabajo utiliza la información basada en datos suministrados por el municipio y algunos apartes del trabajo realizado por el anterior Consultor, ajustando los tópicos que se consideran necesarios para cumplir fielmente con lo exigido con los requisitos establecidos en la Resolución 1045 de 2003, “por la cual se adopta la metodología para la elaboración de los Planes de Gestión Integral de Residuos Sólidos, PGIRS, y se toman otras determinaciones”. Así como lo estableció el documento inicial, este Plan de Gestión Integral de Residuos Sólidos, se desarrollara a partir de un diagnostico integral inicial, de la evaluación de la situación actual para encontrar las debilidades y fortalezas, de la identificación de posibles escenarios futuros, del diseño y puesta en marcha de programas, proyectos y actividades en un plan de acción para el corto, mediano y largo plazo y de la aplicación de un sistema de medición de resultados o programa de seguimiento y monitoreo, que permita avanzar hacia condiciones optimas en un esquema de mejoramiento continuo, teniendo como base la Ley 142 de 1994 y la Política para la Gestión Integral de Residuos establecida por el Gobierno Nacional

Colangioscopia endoscópica de un solo operador en el abordaje diagnóstico integral de los pacientes con estenosis biliar de etiología indeterminada. Experiencia inicial en México

ResumenAntecedentesEl abordaje convencional para el diagnóstico de la ictericia indeterminada está principalmente basado en la colangiografía endoscópica y la citología por cepillado, aunque recientemente se encuentran disponibles otras formas de abordaje como el ultrasonido endoscópico (USE) con o sin aspiración con aguja fina (AAF), biopsia o ultrasonido intraductal y más recientemente la colangioscopia de un solo operador usando el sistema de Spy Glass® con pinza de biopsia.ObjetivoEvaluar la certeza diagnóstica de la colangiografía de un solo operador, USE lineal y/o intraductal (USID), USE+FNA o CPRE+citología por cepillado en pacientes con ictericia de etiología indeterminada.MétodoFue realizado un estudio prospectivo, transversal, comparativo en la Unidad de Endoscopia del Instituto Nacional de Cancerología en una serie consecutiva de pacientes que presentaron ictericia obstructiva de etiología indeterminada. Se les realizó punción con aguja fina con ultrasonido lineal cuando estuvo indicada, entonces se completó el diagnóstico del paciente con colangiografía, USID y cepillado, y se concluyo el estudio de los pacientes con colangioscopia de un solo operador con toma de biopsias bajo visión directa de la zona de mucosa sospechosa. El cálculo de los valores para cada prueba fue realizado como sigue: USE (incluyendo USID), USE+FNA, CPRE+citología por cepillado y colangioscopia con Spy Glass® con biopsia guiada. Los datos demográficos fueron analizados con estadística descriptiva. Todos los procedimientos fueron realizados con los pacientes sometidos a sedación con inducción anestésica con propofol por un anestesista y un grupo de endoscopistas expertos en abordaje pancreatobiliar.ResultadosSe incluyeron un total de 36 pacientes. Los diagnósticos finales fueron los siguientes: 14 colangiocarcinoma, 2 colangitis esclerosante, 7 otras causas benignas y 13 coledocolitiasis. La sensibilidad y la especificidad para cada método fueron como sigue: USE 93.3 y 87.5%; cuando se realizó además FNA+USE la sensibilidad y la especificidad fueron 93.3 y 96.6%; los valores predictivos positivo y negativo para ultrasonido endoscópico fueron 93.3 y 87.5%, y 99.3 y 97.3% cuando se agregó FNA. La certeza diagnóstica final de la combinación de USE+FNA+Spy Glass®+biopsia tuvo una sensibilidad del 99.3% y una especificidad del 97.3% a diferencia del 64.2 y 48.2% respectivamente para el abordaje convencional de CPRE y citología por cepillado. La certeza diagnóstica de la colangioscopia de Spy Glass® con biopsia como procedimiento único fue del 82.3%.ConclusionesLa combinación de USE con o sin FNA, USID y biopsia guiada por colangioscopia de un solo operador con sistema de Spy Glass® incrementa el rendimiento diagnóstico de un 64.2 a un 93.9 con sensibilidades mayores al 96.6 y valor predictivo negativo del 99.3%, comparados con la citología por cepillado y CPRE como abordaje convencional.AbstractBackgroundThe conventional approach to the diagnosis of undetermined obstructive jaundice is endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology. However, other means of diagnosis have recently become available, such as: endoscopic ultrasound (EUS), with or without fine needle aspiration (FNA) biopsy, intraductal ultrasound (IDUS), and most prominently single-operator cholangioscopy using the Spy Glass® system with forceps biopsy.AimTo evaluate the diagnostic accuracy of Spy Glass® cholangioscopy, EUS, with or without IDUS, EUS+FNA to ERCP with brush cytology, in patients presenting with undetermined obstructive jaundice.MethodsA prospective, cross-sectional, comparative study was performed in the Endoscopy Unit of the National Cancer Institute on consecutive patients presenting with undetermined obstructive jaundice. A linear ultrasound-guided fine needle aspiration was performed when indicated. The diagnosis of the patient was then completed with cholangiography. IDUS and brush cytology. The study of patients with single operator cholangioscopy was then concluded with the taking of biopsies of the visually suspicious mucosa using the Spy Glass® and forceps. Performance values for each test were calculated as follows: EUS (including IDUS); EUS+FNA, ERCP with cytology+Spy Glass®-guided biopsy. Descriptive statistics were used for demographic data. All procedures were performed under propofol-induced anesthesia by an anesthesiologist and a group of dedicated pancreatobiliary endoscopists.ResultsA total of 36 patients were included. Final diagnoses were: cholangiocarcinoma in 14, sclerosing cholangitis in 2, other benign causes in 7, and 13 with bile duct stones. Sensitivities and specificities for each method were: 93.3 and 87.5% for EUS. When FNA was added, it was 93.3 and 96.6%. Positive and negative predictive values were 93.3 and 87.5, being 99.3 and 97.3% when FNA was added. The diagnostic accuracy of the combination of EUS (with IDUS)+FNA+Spy Glass® biopsy had a sensitivity and specificity of 93.3% and 96.6%, compared to 64.2 and 48.2%, respectively for “conventional” ERCP+brush. Spy Glass®-guided biopsy alone had an accuracy of 82.3%.ConclusionsThe combination of EUS with/without FNA, IDUS and Spy Glass®-guided forceps biopsy increases the diagnostic yield from 64.2 to 93.9, with sensitivities up to 96.6% and an NPV of 99.3%, compared to “conventional” ERCP+brush

Mutations in ERCC4, Encoding the DNA-Repair Endonuclease XPF, Cause Fanconi Anemia

Fanconi anemia (FA) is a rare genomic instability disorder characterized by progressive bone marrow failure and predisposition to cancer. FA-associated gene products are involved in the repair of DNA interstrand crosslinks (ICLs). Fifteen FA-associated genes have been identified, but the genetic basis in some individuals still remains unresolved. Here, we used whole-exome and Sanger sequencing on DNA of unclassified FA individuals and discovered biallelic germline mutations in ERCC4 (XPF), a structure-specific nuclease-encoding gene previously connected to xeroderma pigmentosum and segmental XFE progeroid syndrome. Genetic reversion and wild-type ERCC4 cDNA complemented the phenotype of the FA cell lines, providing genetic evidence that mutations in ERCC4 cause this FA subtype. Further biochemical and functional analysis demonstrated that the identified FA-causing ERCC4 mutations strongly disrupt the function of XPF in DNA ICL repair without severely compromising nucleotide excision repair. Our data show that depending on the type of ERCC4 mutation and the resulting balance between both DNA repair activities, individuals present with one of the three clinically distinct disorders, highlighting the multifunctional nature of the XPF endonuclease in genome stability and human disease.clos