Repositorio INDICASAT AIP
Not a member yet
227 research outputs found
Sort by
Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015
Full text linkBackground Non-fatal outcomes of disease and injury increasingly detract from the ability of the world’s population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes aff ecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identifi cation and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool fi rst developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores.Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world’s population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes aff ecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identifi cation and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool fi rst developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores
Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015
Full text linkBackground In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015.
Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10–54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantifi ed eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specifi c reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility.Background In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015.
Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10–54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantifi ed eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specifi c reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility
Erratum: Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: The Global Burden of Disease Study 2015 (The Lancet HIV (2016) 3 …
No full textGBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. Lancet HIV 2016; 3: e361–87—In this Article, Kerrie E Doyle and David M Pereira have been added to the list of collaborators and Claudia C Pereira has been removed. These corrections have been made as of Aug 22, 2016.GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. Lancet HIV 2016; 3: e361–87—In this Article, Kerrie E Doyle and David M Pereira have been added to the list of collaborators and Claudia C Pereira has been removed. These corrections have been made as of Aug 22, 2016
TDP-43/FUS in motor neuron disease: complexity and challenges
Full text linkAmyotrophic lateral sclerosis (ALS), a common motor neuron disease affecting two per 100,000 people worldwide, encompasses at least five distinct pathological subtypes, including, ALS-SOD1, ALS-C9orf72, ALS-TDP-43, ALS-FUS and Guam-ALS. The etiology of a major subset of ALS involves toxicity of the TAR DNA-binding protein-43 (TDP-43). A second RNA/DNA binding protein, fused in sarcoma/translocated in liposarcoma (FUS/TLS) has been subsequently associated with about 1% of ALS patients. While mutations in TDP-43 and FUS have been linked to ALS, the key contributing molecular mechanism(s) leading to cell death are still unclear. One unique feature of TDP-43 and FUS pathogenesis in ALS is their nuclear clearance and simultaneous cytoplasmic aggregation in affected motor neurons. Since the discoveries in the last decade implicating TDP-43 and FUS toxicity in ALS, a majority of studies have focused on their cytoplasmic aggregation and disruption of their RNA-binding functions. However, TDP-43 and FUS also bind to DNA, although the significance of their DNA binding in disease-affected neurons has been less investigated. A recent observation of accumulated genomic damage in TDP-43 and FUS-linked ALS and association of FUS with neuronal DNA damage repair pathways indicate a possible role of deregulated DNA binding function of TDP-43 and FUS in ALS. In this review, we discuss the different ALS disease subtypes, crosstalk of etiopathologies in disease progression, available animal models and their limitations, and recent advances in understanding the specific involvement of RNA/DNA binding proteins, TDP-43 and FUS, in motor neuron diseases.Amyotrophic lateral sclerosis (ALS), a common motor neuron disease affecting two per 100,000 people worldwide, encompasses at least five distinct pathological subtypes, including, ALS-SOD1, ALS-C9orf72, ALS-TDP-43, ALS-FUS and Guam-ALS. The etiology of a major subset of ALS involves toxicity of the TAR DNA-binding protein-43 (TDP-43). A second RNA/DNA binding protein, fused in sarcoma/translocated in liposarcoma (FUS/TLS) has been subsequently associated with about 1% of ALS patients. While mutations in TDP-43 and FUS have been linked to ALS, the key contributing molecular mechanism(s) leading to cell death are still unclear. One unique feature of TDP-43 and FUS pathogenesis in ALS is their nuclear clearance and simultaneous cytoplasmic aggregation in affected motor neurons. Since the discoveries in the last decade implicating TDP-43 and FUS toxicity in ALS, a majority of studies have focused on their cytoplasmic aggregation and disruption of their RNA-binding functions. However, TDP-43 and FUS also bind to DNA, although the significance of their DNA binding in disease-affected neurons has been less investigated. A recent observation of accumulated genomic damage in TDP-43 and FUS-linked ALS and association of FUS with neuronal DNA damage repair pathways indicate a possible role of deregulated DNA binding function of TDP-43 and FUS in ALS. In this review, we discuss the different ALS disease subtypes, crosstalk of etiopathologies in disease progression, available animal models and their limitations, and recent advances in understanding the specific involvement of RNA/DNA binding proteins, TDP-43 and FUS, in motor neuron diseases
Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015
Full text linkBackground Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specifi c mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.
Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refi nements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography–year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specifi c mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specifi c mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors aff ecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specifi c mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.
Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refi nements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography–year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specifi c mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specifi c mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors aff ecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER)
Revisiting metal toxicity in neurodegenerative diseases and stroke: Therapeutic potential.
Full text linkExcessive accumulation of pro-oxidant metals, observed in affected brain regions, has consistently been implicated as a ontributor to the brain pathology including neurodegenerative diseases and acute injuries such as stroke. Furthermore, the potential interactions between metal toxicity and other commonly associated etiological factors, such as misfolding/aggregation of amyloidogenic proteins or genomic damage, are poorly understood. Decades of research provide compelling evidence implicating metal overload in neurological diseases and stroke. However, the utility of metal toxicity as a therapeutic target is controversial, possibly due to a lack of comprehensive understanding of metal dyshomeostasis-mediated neuronal pathology. In this article, we discuss the current understanding of metal toxicity and the challenges associated with metal-targeted therapies.Excessive accumulation of pro-oxidant metals, observed in affected brain regions, has consistently been implicated as a ontributor to the brain pathology including neurodegenerative diseases and acute injuries such as stroke. Furthermore, the potential interactions between metal toxicity and other commonly associated etiological factors, such as misfolding/aggregation of amyloidogenic proteins or genomic damage, are poorly understood. Decades of research provide compelling evidence implicating metal overload in neurological diseases and stroke. However, the utility of metal toxicity as a therapeutic target is controversial, possibly due to a lack of comprehensive understanding of metal dyshomeostasis-mediated neuronal pathology. In this article, we discuss the current understanding of metal toxicity and the challenges associated with metal-targeted therapies
The genome of Leishmania panamensis: insights into genomics of the L. (Viannia) subgenus.
Full text linkKinetoplastid parasites of the Leishmania genus cause several forms of leishmaniasis. Leishmania species pathogenic to human are separated into two subgenera, Leishmania (Leishmania) and L. (Viannia). Species from the Viannia subgenus cause predominantly cutaneous leishmaniasis in Central and South America, occasionally leading to more severe clinical presentations. Although the genomes of several species of Leishmania have been sequenced to date, only one belongs to this rather different subgenus. Here we explore the unique features of the Viannia subgenus by sequencing and analyzing the genome of L. (Viannia) panamensis. Against a background of conservation in gene content and synteny, we found key differences at the genomic level that may explain the occurrence of molecular processes involving nucleic acid manipulation and differential modification of surface glycoconjugates. These differences may in part explain some phenotypic characteristics of the Viannia parasites, including their increased adaptive capacity and enhanced metastatic ability.Kinetoplastid parasites of the Leishmania genus cause several forms of leishmaniasis. Leishmania species pathogenic to human are separated into two subgenera, Leishmania (Leishmania) and L. (Viannia). Species from the Viannia subgenus cause predominantly cutaneous leishmaniasis in Central and South America, occasionally leading to more severe clinical presentations. Although the genomes of several species of Leishmania have been sequenced to date, only one belongs to this rather different subgenus. Here we explore the unique features of the Viannia subgenus by sequencing and analyzing the genome of L. (Viannia) panamensis. Against a background of conservation in gene content and synteny, we found key differences at the genomic level that may explain the occurrence of molecular processes involving nucleic acid manipulation and differential modification of surface glycoconjugates. These differences may in part explain some phenotypic characteristics of the Viannia parasites, including their increased adaptive capacity and enhanced metastatic ability
Phytochemical composition, antiparasitic and α–glucosidase inhibition activities from Pelliciera rhizophorae
Full text linkPanama has an extensive mangrove area and it is one of the countries with the highest biodiversity in America. Mangroves are widely used in traditional medicine, nevertheless, there are very few studies that validates their medicinal properties in America. Given the urgent need for therapeutic options to treat several diseases of public health importance, mangrove ecosystem could be an interesting source of new bioactive molecules. This study was designed to evaluate the potential of Pelliciera rhizophorae as a source of bioactive compoundsPanama has an extensive mangrove area and it is one of the countries with the highest biodiversity in America. Mangroves are widely used in traditional medicine, nevertheless, there are very few studies that validates their medicinal properties in America. Given the urgent need for therapeutic options to treat several diseases of public health importance, mangrove ecosystem could be an interesting source of new bioactive molecules. This study was designed to evaluate the potential of Pelliciera rhizophorae as a source of bioactive compound
α-Synuclein misfolding versus aggregation relevance to Parkinson’s disease: Critical assessment and modeling
Full text linkα-Synuclein, an abundant and conserved presynaptic brain protein, is implicated as a critical factor in
Parkinson’s disease (PD). The aggregation of α-synuclein isbelieved to be a critical event in the isease process. α-Synuclein is characterized by a remarkable conformational plasticity, adopting different
onformations depending on the environment. Therefore, it is classified as an “intrinsically disordered protein.” Recently, a debate has challenged theview on the intrinsically disordered behavior of α-synuclein in the cell. It has been proposed that α-synuclein is a stable tetramer with a low propensity for aggregation; however, its destabilization leads to protein misfolding and its aggregation kinetics. In our critical analysis, we discussed about major issues: (i) why α-synuclein conformational behavior does not fit into the normal secondary structural characteristics of proteins, (ii) potential amino acids involved in the complexity of misfolding in α-synuclein that leads to aggregation, and (iii) the role of metals in misfolding and aggregation. To evaluate the above critical issues, we developed
ioinformatics models related to secondary and tertiary conformations, Ramachandran plot, free energy change, intrinsic disordered prediction, solvent accessibility, and FoldIndex pattern. To the best of our knowledge, this is a novel critical assessment to understand the misfolding biology of synuclein and its relevance to Parkinson’s disease.α-Synuclein, an abundant and conserved presynaptic brain protein, is implicated as a critical factor in
Parkinson’s disease (PD). The aggregation of α-synuclein isbelieved to be a critical event in the isease process. α-Synuclein is characterized by a remarkable conformational plasticity, adopting different
onformations depending on the environment. Therefore, it is classified as an “intrinsically disordered protein.” Recently, a debate has challenged theview on the intrinsically disordered behavior of α-synuclein in the cell. It has been proposed that α-synuclein is a stable tetramer with a low propensity for aggregation; however, its destabilization leads to protein misfolding and its aggregation kinetics. In our critical analysis, we discussed about major issues: (i) why α-synuclein conformational behavior does not fit into the normal secondary structural characteristics of proteins, (ii) potential amino acids involved in the complexity of misfolding in α-synuclein that leads to aggregation, and (iii) the role of metals in misfolding and aggregation. To evaluate the above critical issues, we developed
ioinformatics models related to secondary and tertiary conformations, Ramachandran plot, free energy change, intrinsic disordered prediction, solvent accessibility, and FoldIndex pattern. To the best of our knowledge, this is a novel critical assessment to understand the misfolding biology of synuclein and its relevance to Parkinson’s disease
Geographic Expansion of the Invasive Mosquito Aedes albopictus across Panama— Implications for Control of Dengue and Chikungunya Viruses
Full text linkThe Asian tiger mosquito, Aedes (Stegomyia) albopictus, is an invasive species that has expanded its territory to over 40% of the earth’s terrestrial landmass in the last 30 years [1]. Ae. albopictus is an efficient vector of all serotypes of dengue, a disease that has increased in frequency over the past 30 years in the Americas [2], where it represents an annual cost of 2,100,000,000 USD per year [3]. This mosquito is also an efficient vector of the three genotypes of Chikungunya virus, a worldwide emerging pathogen that causes fever, fatigue, and joint swelling in humans. Since 2006, Chikungunya outbreaks have been increasingly recorded outside the virus’s native range in tropical Africa, perhaps because of a mutation in the virus’s envelope gene, which increases the replication and dissemination capacity of the virus in Ae. albopictus [4]. During the second quarter of 2014, Chikungunya has been detected throughout much of the Americas, with major outbreaks occurring in several Caribbean nations, and local transmission confirmed or suspected in the United States, Panama, Venezuela, Peru, and Chile, creating an imminent threat for humans throughout the Americas, who have no prior exposure to this infection [5]. The first cases of Chikungunya disease in Panama were reported in May 2014, occurring in nonresidents who most likely picked up the virus in their Caribbean countries of origin. On 23 July 2014, Panama’s health authority reported autochthonous transmission of Chikungunya virus. Coincidentally, the earliest cases involved patients located in Juan Diaz, an urban area on the eastern outskirts of Panama City, where the first specimen of invasive Ae. albopictus was collected in 2002. Ae. albopictus has expanded across much of Panama since that time, yet to date, no information exists about the degree of expansion or about the factors contributing to the geographic expansion of this important mosquito vector across Panama. Here, we map the temporal expansion of Ae. albopictus, use species distribution models to determine the ecological and nonecological factors associated with its expansion, and comment on the implications for vector and disease control programs in Panama and elsewhere in the American tropics.The Asian tiger mosquito, Aedes (Stegomyia) albopictus, is an invasive species that has expanded its territory to over 40% of the earth’s terrestrial landmass in the last 30 years [1]. Ae. albopictus is an efficient vector of all serotypes of dengue, a disease that has increased in frequency over the past 30 years in the Americas [2], where it represents an annual cost of 2,100,000,000 USD per year [3]. This mosquito is also an efficient vector of the three genotypes of Chikungunya virus, a worldwide emerging pathogen that causes fever, fatigue, and joint swelling in humans. Since 2006, Chikungunya outbreaks have been increasingly recorded outside the virus’s native range in tropical Africa, perhaps because of a mutation in the virus’s envelope gene, which increases the replication and dissemination capacity of the virus in Ae. albopictus [4]. During the second quarter of 2014, Chikungunya has been detected throughout much of the Americas, with major outbreaks occurring in several Caribbean nations, and local transmission confirmed or suspected in the United States, Panama, Venezuela, Peru, and Chile, creating an imminent threat for humans throughout the Americas, who have no prior exposure to this infection [5]. The first cases of Chikungunya disease in Panama were reported in May 2014, occurring in nonresidents who most likely picked up the virus in their Caribbean countries of origin. On 23 July 2014, Panama’s health authority reported autochthonous transmission of Chikungunya virus. Coincidentally, the earliest cases involved patients located in Juan Diaz, an urban area on the eastern outskirts of Panama City, where the first specimen of invasive Ae. albopictus was collected in 2002. Ae. albopictus has expanded across much of Panama since that time, yet to date, no information exists about the degree of expansion or about the factors contributing to the geographic expansion of this important mosquito vector across Panama. Here, we map the temporal expansion of Ae. albopictus, use species distribution models to determine the ecological and nonecological factors associated with its expansion, and comment on the implications for vector and disease control programs in Panama and elsewhere in the American tropics