Structural inequality and temporal brain dynamics across diverse samples.

BACKGROUND: Structural income inequality - the uneven income distribution across regions or countries - could affect brain structure and function, beyond individual differences. However, the impact of structural income inequality on the brain dynamics and the roles of demographics and cognition in these associations remains unexplored. METHODS: Here, we assessed the impact of structural income inequality, as measured by the Gini coefficient on multiple EEG metrics, while considering the subject-level effects of demographic (age, sex, education) and cognitive factors. Resting-state EEG signals were collected from a diverse sample (countries = 10; healthy individuals = 1394 from Argentina, Brazil, Colombia, Chile, Cuba, Greece, Ireland, Italy, Turkey and United Kingdom). Complexity (fractal dimension, permutation entropy, Wiener entropy, spectral structure variability), power spectral and aperiodic components (1/f slope, knee, offset), as well as graph-theoretic measures were analysed. FINDINGS: Despite variability in samples, data collection methods, and EEG acquisition parameters, structural inequality systematically predicted electrophysiological brain dynamics, proving to be a more crucial determinant of brain dynamics than individual-level factors. Complexity and aperiodic activity metrics captured better the effects of structural inequality on brain function. Following inequality, age and cognition emerged as the most influential predictors. The overall results provided convergent multimodal metrics of biologic embedding of structural income inequality characterised by less complex signals, increased random asynchronous neural activity, and reduced alpha and beta power, particularly over temporoposterior regions. CONCLUSION: These findings might challenge conventional neuroscience approaches that tend to overemphasise the influence of individual-level factors, while neglecting structural factors. Results pave the way for neuroscience-informed public policies aimed at tackling structural inequalities in diverse populations.

Educational disparities in brain health and dementia across Latin America and the United States.

BACKGROUND: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. METHODS: A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. RESULTS: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. DISCUSSION: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. HIGHLIGHTS: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.

Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging.

Brain clocks capture diversity and disparity in aging and dementia.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R2=0.37, F2=0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.

Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

Aberrant AHRR, ADAMTS2 and FAM184 DNA Methylation: Candidate Biomarkers in the Oral Rinse of Heavy Smokers.

OBJECTIVE: To identify DNA methylation patterns of heavy smokers in oral rinse samples. METHODS: Genome-wide DNA methylation data was imported from Gene Expression Omnibus GSE70977 using the GEOquery package. Two independent sets were analyzed: (a) 71 epigenomes of cancer-free subjects (heavy smokers n = 37 vs. non-smokers n = 31); for concordance assessment (b) 139 oral-cancer patients' epigenomes (heavy smokers n = 92 vs. non-smokers n = 47). Differential DNA methylation for CpG positions and at the regional level was determined using Limma and DMRcate Bioconductor packages. The linear model included sex, age, and alcohol consumption. The statistical threshold was set to p < 0.05. Functional gene prioritization analysis was performed for gene-targeted analysis. RESULTS: In individuals without cancer and heavy smokers, the FAM184B gene was found with two CpG positions differentially hypermethylated (p = 0.012 after FDR adjustment), in a region of 48 bp with an absolute methylation difference >10% between groups (p = 1.76 × 10-8). In the analysis corresponding to oral-cancer patients, we found AHRR differentially hypomethylated cancer patients, but also in subjects without oral cancer in the targeted analyses. Remarkably, ADAMTS2 was found differentially hypermethylated in heavy smokers without a diagnosis of cancer in two consecutive probes cg05575921 (p = 3.13 × 10-7) and cg10208897 (p = 1.36 × 10-5). CONCLUSIONS: Differentially methylated AHRR, ADAMTS2, and FAM184B genes are biomarker candidates in oral rinse samples.

Biomarkers of Periodontitis and Its Differential DNA Methylation and Gene Expression in Immune Cells: A Systematic Review.

The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: MAP3K7, MYD88, IL6R, RIPK2, FADD, IRAK1BP1, and PPARA in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. TGFB1I1, VNN1, HLADRB4, and CXCL8 genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The DAB2 gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.

Near Real-Time Telemetry of Nation-Wide ICU's Capacity Strain in Argentina.

Due to the fast-spreading of COVID-19 during the pandemic, decision-makers turned into innovative digital solutions for data collection in order to make well-informed public health decisions based on reliable data from verified sources. This work describes one of such solutions, implemented in partnership with the Ministry of Health in Argentina.

[Congenital cytomegalovirus infection screening in high risk newborn]. / Cribado de infección por citomegalovirus congénito en recién nacidos de alto riesgo.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is the most frequent cause of congenital infection, 90% of affected newborn (NB) are asymptomatic at birth and 6-15% will develop long term sequalae. It is the main etiology of non-genetic sensorineural hearing loss. AIM: To determine prevalence of CMV in high risk NB. METHODS: Cohort prospective study, including inpatient NB with one or more of following criteria: birth weight < 1,500 g, < 32 weeks gestational age (GA), severe small for gestational age (SGA), suspected congenital infection or "refer" in newborn hearing test, also NB to HIV-infected mothers. Urine CMV polymerase chain reaction was performed within 21 day of life. RESULTS: 193 NB were enrolled. Global cCMV prevalence 2.6% (n: 5) and by risk group: one third (n: 1) in NB with suspected congenital infection, 8.3% in NB with "refer" result in hearing test, 4.9% in NB to HIV-infected mothers, 3.3% in severe SGA and 1.7% in < 1,500 g, none with significant association. Only one symptomatic cCMV was detected who died in neonatal period and the remaining (asymptomatic) cCMV patients have normal hearing follow-up. DISCUSSION: Reported prevalence was comparable to international reports. We recommend cCMV screening, at least in risk groups, being ideal the universal screening. This would allow timely treatment and active follow-up.

ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome-wide DNA methylation pilot study.

OBJECTIVE: To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis. BACKGROUND: The DNA methylation profiling of peripheral leukocytes as immune-related tissue potentially relevant as a source of biomarkers between periodontitis patients and gingivally healthy subjects has not been investigated. METHODS: A DNA methylation epigenome-wide study of peripheral leukocytes was conducted using the Illumina MethylationEPIC platform in sixteen subjects, eight diagnosed with periodontitis patients and eight age-matched and sex-matched periodontally healthy controls. A trained periodontist performed the clinical evaluation. Global DNA methylation was estimated using methylation-sensitive high-resolution melting in LINE1. Routine cell count cytometry and metabolic laboratory tests were also performed. The analysis of differentially methylated positions (DMPs) and differentially methylated regions (DMRs) was made using R/Bioconductor environment considering leukocyte populations assessed in both routine cell counts and using the FlowSorted.Blood.EPIC package. Finally, a DMP and DMR intersection analysis was performed. Functional enrichment analysis was carried out with the differentially methylated genes found in DMP. RESULTS: DMP analysis identified 81 differentially hypermethylated genes and 21 differentially hypomethylated genes. Importantly, the intersection analysis showed that zinc finger protein 718 (ZNF718) and homeobox A4 (HOXA4) were differentially hypermethylated and zinc finger protein 57 (ZFP57) was differentially hypomethylated in periodontitis. The functional enrichment analysis found clearly immune-related ontologies such as "detection of bacterium" and "antigen processing and presentation." CONCLUSION: The results of this study propose three new periodontitis-related genes: ZNF718, HOXA4, and ZFP57 but also evidence the suitability and relevance of studying leukocytes' DNA methylome for biological interpretation of systemic immune-related epigenetic patterns in periodontitis.

Cribado de infección por citomegalovirus congénito en recién nacidos de alto riesgo / Congenital cytomegalovirus infection screening in high risk newborn

INTRODUCCIÓN: La infección congénita por citomegalovirus (CMVc) es la causa más frecuente de infección intrauterina, 90% de los recién nacidos (RN) son asintomáticos al nacer y 6 a 15% desarrollarán secuelas a largo plazo, siendo la principal etiología de hipoacusia sensorio-neural no-genética. OBJETIVO: Determinar la prevalencia de CMVc en RN de alto riesgo. PACIENTES Y MÉTODO: Estudio de cohorte prospectivo, incluyó RN hospitalizados, con uno o más de los siguientes criterios: peso de nacimiento < 1.500 g, < 32 semanas edad gestacional (EG), pequeños para edad gestacional (PEG) severos, sospecha de infección congénita o que "no pasan" en estudio auditivo al nacer, además de hijos de madre con infección por VIH. Se realizó reacción de polimerasa en cadena para CMV en orina antes de 21 días de vida. RESULTADOS: Se enrolaron 193 RN. Prevalencia global CMVc 2,6% (n: 5) y por grupo de riesgo: 1/3 (n: 1) en RN con sospecha activa de infección congénita, 8,3% en RN con resultado "no pasa" en estudio auditivo, 4,9% en hijos de madre con infección por VIH, 3,3% en PEG severo y 1,7% < 1500 g, ninguno con asociación significativa. Sólo un paciente con CMVc fue sintomático, quien falleció en el período neonatal y los restantes RN con CMVc (asintomáticos) tienen seguimiento auditivo normal. DISCUSIÓN: La prevalencia reportada es comparable a las internacionales. Recomendamos cribado de CMVc, al menos en grupos de riesgo, siendo lo ideal el cribado universal. Esto permitiría su tratamiento oportuno y un seguimiento activo.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is the most frequent cause of congenital infection, 90% of affected newborn (NB) are asymptomatic at birth and 6-15% will develop long term sequalae. It is the main etiology of non-genetic sensorineural hearing loss. AIM: To determine prevalence of CMV in high risk NB. Methods: Cohort prospective study, including inpatient NB with one or more of following criteria: birth weight < 1,500 g, < 32 weeks gestational age (GA), severe small for gestational age (SGA), suspected congenital infection or "refer" in newborn hearing test, also NB to HIV-infected mothers. Urine CMV polymerase chain reaction was performed within 21 day of life. RESULTS: 193 NB were enrolled. Global cCMV prevalence 2.6% (n: 5) and by risk group: one third (n: 1) in NB with suspected congenital infection, 8.3% in NB with "refer" result in hearing test, 4.9% in NB to HIV-infected mothers, 3.3% in severe SGA and 1.7% in < 1,500 g, none with significant association. Only one symptomatic cCMV was detected who died in neonatal period and the remaining (asymptomatic) cCMV patients have normal hearing follow-up. DISCUSSION: Reported prevalence was comparable to international reports. We recommend cCMV screening, at least in risk groups, being ideal the universal screening. This would allow timely treatment and active follow-up.

[Temporal trend and spatial distribution of mortality from neglected tropical diseases in Argentina 1991-2016Tendência temporal e distribuição espacial da mortalidade por doenças tropicais negligenciadas na Argentina entre 1991 e 2016]. / Tendencia temporal y distribución espacial de la mortalidad por enfermedades tropicales desatendidas en Argentina entre 1991 y 2016.

OBJECTIVE: Determine the mortality from neglected tropical diseases (NTD) in Argentina from 1991 to 2016, their overall temporal trend and the trend for the most frequent causes by age and sex. METHODS: Argentina's crude age-specific and age-adjusted mortality from NTDs were calculated for the period 1991-2016. The temporal trend was analyzed using joinpoint regression models. RESULTS: Mortality from NTDs is a phenomenon observed primarily in people over 50 and men. The trend in the age-adjusted NTD death rates shows a statistically significant decline between 1991 and 2016, with an average annual percentage change (AAPC) for both sexes of -3.98 (CI 95%: -4.69; -3.25). In terms of the selected diseases, a steady decline in the rates for echinococcus is observed in the period 1991-2016, while two periods can be identified for Chagas, one in which the decline is significant (1991-2008) and another in which it is not (2008-2016). With regard to leprosy, a period with a sharp and significant increase is observed (1991-1998), followed by another period (1998-2016) of significant moderate decline. With the exception of echinococcus, the selected diseases are found basically in northwestern and northeastern Argentina. CONCLUSIONS: The downward trend in mortality from NTDs is significant for both sexes. It is clear that despite the decline in recent years, mortality from NTDs is an important public health problem.

OBJETIVO: Descrever a mortalidade por doenças tropicais negligenciadas na Argentina entre 1991 e 2016 assim como a tendência temporal geral e as causas mais comuns de mortalidade desagregadas por idade e sexo. MÉTODOS: Foi realizado o cálculo das taxas de mortalidade brutas por doenças tropicais negligenciadas, específicas por faixa etária e padronizadas por idade, na Argentina para o período de 1991 a 2016. A tendência temporal foi analisada com o uso de modelos de regressão joinpoint. RESULTADOS: A mortalidade por doenças tropicais negligenciadas ocorre sobretudo em indivíduos do sexo masculino acima dos 50 anos. A análise da tendência das taxas de mortalidade por doenças tropicais negligenciadas padronizadas por idade demonstra uma redução estatisticamente significativa entre 1991 e 2016, com variação percentual média anual (AAPC) em ambos os sexos de ­3,98 (IC 95% ­4,69; ­3,25). Com relação a doenças específicas, houve uma redução contínua das taxas de mortalidade por equinococose entre 1991 e 2016; para a doença de Chagas, podem ser identificados dois períodos, um de redução significativa (1991­2008) e outro sem redução (2008­2016) e, para hanseníase, houve um período de aumento súbito significativo (1991­1998) seguido por uma redução moderada significativa entre 1998 e 2016. Estas doenças, à exceção da equinococose, estão principalmente distribuídas nas regiões noroeste e nordeste do país. CONCLUSÕES: Verifica-se uma tendência de declínio significativo da mortalidade por doenças tropicais negligenciadas em ambos os sexos. Deve-se salientar que, apesar da redução ocorrida nos últimos anos, a mortalidade por doenças tropicais negligenciadas continua sendo um importante problema de saúde pública na Argentina.

Tendencia temporal y distribución espacial de la mortalidad por enfermedades tropicales desatendidas en Argentina entre 1991 y 2016

[RESUMEN]. Objetivo. Conocer la mortalidad por enfermedades tropicales desatendidas (ETD) de Argentina entre 1991 y 2016 y su tendencia temporal general y para las causas más frecuentes por edad y sexo. Métodos. Se calcularon las tasas de mortalidad por ETD brutas, específicas por edad y ajustadas por edad de Argentina para el período 1991-2016. Se realizó el análisis de la tendencia temporal mediante modelos de regresión joinpoint. Resultados. La mortalidad por ETD afecta principalmente a personas mayores de 50 años y a hombres. La tendencia de las tasas de mortalidad ajustadas por edad por ETD muestran un descenso estadísticamente significativo entre 1991 y 2016, con porcentaje medio de cambio anual (AAPC) para ambos sexos de -3,98 (IC 95%: -4,69; -3,25). Respecto a las enfermedades seleccionadas, la equinococosis muestra un descenso continuo de las tasas entre 1991-2016, mientras que en la enfermedad de Chagas pueden identificarse dos períodos, uno de descenso significativo (1991-2008) y otro no (2008-2016). En cuanto a la lepra, se observa un período de incremento brusco y significativo (1991-1998) seguido por otro período entre 1998-2016 de descenso significativo moderado. Las enfermedades seleccionadas se distribuyen fundamentalmente en el noroeste y noreste argentino, a excepción de la equinococosis. Conclusiones. Es significativa la tendencia decreciente de la mortalidad por ETD para ambos sexos. Se pone de relieve que, pese al descenso de los últimos años, la mortalidad por ETD representa un importante problema de salud pública.

[ABSTRACT]. Objective. Determine the mortality from neglected tropical diseases (NTD) in Argentina from 1991 to 2016, their overall temporal trend and the trend for the most frequent causes by age and sex. Methods. Argentina’s crude age-specific and age-adjusted mortality from NTDs were calculated for the period 1991-2016. The temporal trend was analyzed using joinpoint regression models. Results. Mortality from NTDs is a phenomenon observed primarily in people over 50 and men. The trend in the age-adjusted NTD death rates shows a statistically significant decline between 1991 and 2016, with an average annual percentage change (AAPC) for both sexes of -3.98 (CI 95%: -4.69; -3.25). In terms of the selected diseases, a steady decline in the rates for echinococcus is observed in the period 1991-2016, while two periods can be identified for Chagas, one in which the decline is significant (1991-2008) and another in which it is not (2008-2016). With regard to leprosy, a period with a sharp and significant increase is observed (1991-1998), followed by another period (1998-2016) of significant moderate decline. With the exception of echinococcus, the selected diseases are found basically in northwestern and northeastern Argentina. Conclusions. The downward trend in mortality from NTDs is significant for both sexes. It is clear that despite the decline in recent years, mortality from NTDs is an important public health problem.

[RESUMO]. Objetivo. Descrever a mortalidade por doenças tropicais negligenciadas na Argentina entre 1991 e 2016 assim como a tendência temporal geral e as causas mais comuns de mortalidade desagregadas por idade e sexo. Métodos. Foi realizado o cálculo das taxas de mortalidade brutas por doenças tropicais negligenciadas, específicas por faixa etária e padronizadas por idade, na Argentina para o período de 1991 a 2016. A tendência temporal foi analisada com o uso de modelos de regressão joinpoint. Resultados. A mortalidade por doenças tropicais negligenciadas ocorre sobretudo em indivíduos do sexo masculino acima dos 50 anos. A análise da tendência das taxas de mortalidade por doenças tropicais negligenciadas padronizadas por idade demonstra uma redução estatisticamente significativa entre 1991 e 2016, com variação percentual média anual (AAPC) em ambos os sexos de –3,98 (IC 95% –4,69; –3,25). Com relação a doenças específicas, houve uma redução contínua das taxas de mortalidade por equinococose entre 1991 e 2016; para a doença de Chagas, podem ser identificados dois períodos, um de redução significativa (1991–2008) e outro sem redução (2008–2016) e, para hanseníase, houve um período de aumento súbito significativo (1991–1998) seguido por uma redução moderada significativa entre 1998 e 2016. Estas doenças, à exceção da equinococose, estão principalmente distribuídas nas regiões noroeste e nordeste do país. Conclusões. Verifica-se uma tendência de declínio significativo da mortalidade por doenças tropicais negligenciadas em ambos os sexos. Deve-se salientar que, apesar da redução ocorrida nos últimos anos, a mortalidade por doenças tropicais negligenciadas continua sendo um importante problema de saúde pública na Argentina.

Alzheimer's disease DNA methylome of pyramidal layers in frontal cortex: laser-assisted microdissection study.

OBJECTIVE: To study DNA methylation patterns of cortical pyramidal layers susceptible to late-onset Alzheimer's disease (LOAD) neurodegeneration. METHODS: Laser-assisted microdissection to select pyramidal layers' cells in frontal cortex of 32 human brains (18 LOAD) and Infinium DNA Methylation 450K analysis were performed to find differential methylated positions and regions, in addition to the corresponding gene set functional enrichment analyses. RESULTS: Differential hypermethylation in several genomic regions and genes mainly in HOXA3, GSTP1, CXXC1-3 and BIN1. The functional enrichment analysis revealed genes significantly related to oxidative-stress and synapsis. CONCLUSION: The present results indicate the differentially methylated genes related to neural projections, synapsis, oxidative stress and epigenetic regulator genes and represent the first epigenome of cortical pyramidal layers in LOAD.

Cambios contemporáneos de la fecundidad en Argentina / Contemporary changes in fertility in Argentina

INTRODUCCIÓN Las particularidades del proceso de cambio demográfico en Argentina proporcionan un escenario privilegiado para profundizar el estudio del descenso reciente de la fecundidad y evaluar si Argentina se encuentra en transición hacia un régimen basado en nuevos patrones de intensidad y calendario y, en particular, observar cuáles fueron los cambios en estos aspectos a nivel sub-nacional. OBJETIVOS Construir una base de datos harmonizada [sic] sobre la fecundidad en Argentina según provincias y departamentos, con el fin de proporcionar una herramienta para investigadores, estudiantes y el público en general, interesado en conocer las tendencias y procesos sub-nacionales contemporáneos de la fecundidad en el país. METODOS Se utilizaron las definiciones de las variables explicitadas en los anuarios de la DEIS. RESULTADOS Se contruyó una base de datos armonizada de nacimientos en la Argentina a nivel subnacional para el periodo 1980-2014. DISCUSIÓN La coyuntura actual permitirá además abordar distintas hipótesis acerca del proceso histórico de cambio de la fecundidad, que las aproximaciones teóricas (y los estudios empíricos previos) ponderan en distinta medida como determinadas y determinantes de largo plazo de los procesos de cambio social, de desarrollo económico (asociadas a su vez a distintas etapas de la transición demográfica) y de los cambios en los Sistemas y Políticas de Salud

[Time-trend analysis of diabetes mellitus mortality in Argentina, 1990-2013]. / Análisis de la tendencia temporal de la mortalidad por diabetes mellitus en Argentina, 1990-2013.

OBJECTIVES: To describe the time trend of mortality attributable to diabetes mellitus (DM) in Argentina in the years 1990-2013, by age and sex. METHODS: Crude, age-specific, and age-adjusted rates of DM mortality in Argentina were calculated for the period 1990-2013. Mortality data were obtained from the Statistical Report on Deaths issued by the Department of Statistics and Health Information. An analysis of this trend was carried out through joinpoint regression models. RESULTS: Analysis of the trend of crude and age-adjusted DM mortality rates yielded a statistically significant model in which mortality increased between 1990 and 2001 and declined thereafter. Furthermore, for age-adjusted rates, there was a significant downward trend of mortality in women (AAPC -1.10, 95%CI -1.70 to -0.50). Age-specific mortality rates multiplied with every 10-year increment in age. All age groups older than 50 years showed a growing mortality trend between 1990 and 2001. CONCLUSIONS: DM mortality mainly affects people over the age of 50 and men. A significant downward trend in age-adjusted DM mortality rates was observed for women. These findings highlight the importance of developing policies for prevention and early detection, as well as of proper coding of multiple causes of death.

Análisis de la tendencia temporal de la mortalidad por diabetes mellitus en Argentina, 1990-2013 / Time-trend analysis of diabetes mellitus mortality in Argentina, 1990-2013 / Análise da tendência temporal da mortalidade por diabetes mellitus na Argentina, 1990–2013

Objetivos. El objetivo de este trabajo es describir la tendencia temporal de la mortalidad por Diabetes Mellitus (DM) en la Argentina en el período comprendido entre 1990 y 2013, por edad y sexo. Métodos. Se calcularon las tasas brutas, específicas por edad y ajustadas por edad de mortalidad por DM en la Argentina para el período 1990-2013. Los datos de mortalidad se obtuvieron del Informe Estadístico de Defunción de la Dirección de Estadísticas e Información de Salud. Se realizó un análisis de la tendencia mediante modelos de regresión joinpoint. Resultados. El análisis de la tendencia de las tasas brutas y ajustadas por edad de mortalidad por DM muestra un modelo estadísticamente significativo en el que se produce un incremento en la mortalidad entre 1990 y 2001, momento a partir del cual puede observarse un descenso. Asimismo, para las tasas ajustadas por edad se encuentra una tendencia significativa de descenso de la mortalidad para mujeres (AAPC: -1,10, IC 95%: -1,70; -0,50). Las tasas de mortalidad específicas por edad se multiplican cada 10 años de edad. Todos los grupos de edad mayores de 50 años muestran una tendencia creciente entre 1990 y 2001. Conclusiones. La mortalidad por DM afecta principalmente a personas mayores de 50 años y a hombres. Es significativa la tendencia decreciente en las tasas ajustadas de mortalidad por DM para mujeres. Se subraya la importancia de desarrollar políticas de prevención y de detección temprana, como así también la codificación de la muerte por múltiples causas.

Objectives: To describe the time trend of mortality attributable to diabetes mellitus (DM) in Argentina in the years 1990-2013, by age and sex. Methods: Crude, age-specific, and age-adjusted rates of DM mortality in Argentina were calculated for the period 1990-2013. Mortality data were obtained from the Statistical Report on Deaths issued by the Department of Statistics and Health Information. An analysis of this trend was carried out through joinpoint regression models. Results: Analysis of the trend of crude and age-adjusted DM mortality rates yielded a statistically significant model in which mortality increased between 1990 and 2001 and declined thereafter. Furthermore, for age-adjusted rates, there was a significant downward trend of mortality in women (AAPC -1.10, 95%CI -1.70 to -0.50). Agespecific mortality rates multiplied with every 10-year increment in age. All age groups older than 50 years showed a growing mortality trend between 1990 and 2001. Conclusions: DM mortality mainly affects people over the age of 50 and men. A significant downward trend in age-adjusted DM mortality rates was observed for women. These findings highlight the importance of developing policies for prevention and early detection, as well as of proper coding of multiple causes of death.

Objetivos: Descrever a tendência temporal da mortalidade por diabetes mellitus (DM) na Argentina no período entre 1990 e 2013, por idade e sexo. Métodos: Foram estimados os índices de mortalidade por DM brutos por idade e ajustados por idade na Argentina para o período 1990–2013. Os dados de mortalidade foram obtidos do Relatório estatístico de óbitos elaborado pelo Núcleo de Estatísticas e Informação em Saúde. Foi realizada uma análise da tendência com o uso de modelos de regressão por joinpoint. Resultados: A análise da tendência dos índices de mortalidade por DM brutos e ajustados por idade indica um modelo estatisticamente significativo com aumento da mortalidade entre 1990 e 2001, ponto a partir do qual é observado um declínio. Com relação aos índices ajustados por idade, verifica-se uma tendência significativa de declínio da mortalidade no sexo feminino (AAPC: –1,10, IC 95%: –1,70; –0,50). Os índices de mortalidade por idade são multiplicados a cada 10 anos de idade. Verifica-se uma tendência crescente em todas as faixas etárias acima de 50 anos entre 1990 e 2001. Conclusões: A mortalidade por DM atinge principalmente indivíduos do sexo masculino e com idade acima de 50 anos. É significativa a tendência decrescente nos índices de mortalidade por DM ajustados no sexo feminino. Destaca-se a importância de desenvolver políticas de prevenção e detecção precoce e da codificação dos óbitos por múltiplas causas.

Análisis de la tendencia temporal de la mortalidad por diabetes mellitus en Argentina, 1990-2013 / Time-trend analysis of diabetes mellitus mortality in Argentina, 1990-2013 / Análise da tendência temporal da mortalidade por diabetes mellitus na Argentina, 1990-2013

RESUMEN Objetivos El objetivo de este trabajo es describir la tendencia temporal de la mortalidad por Diabetes Mellitus (DM) en la Argentina en el período comprendido entre 1990 y 2013, por edad y sexo. Métodos Se calcularon las tasas brutas, específicas por edad y ajustadas por edad de mortalidad por DM en la Argentina para el período 1990-2013. Los datos de mortalidad se obtuvieron del Informe Estadístico de Defunción de la Dirección de Estadísticas e Información de Salud. Se realizó un análisis de la tendencia mediante modelos de regresión joinpoint. Resultados El análisis de la tendencia de las tasas brutas y ajustadas por edad de mortalidad por DM muestra un modelo estadísticamente significativo en el que se produce un incremento en la mortalidad entre 1990 y 2001, momento a partir del cual puede observarse un descenso. Asimismo, para las tasas ajustadas por edad se encuentra una tendencia significativa de descenso de la mortalidad para mujeres (AAPC: -1,10, IC 95%: -1,70; -0,50). Las tasas de mortalidad específicas por edad se multiplican cada 10 años de edad. Todos los grupos de edad mayores de 50 años muestran una tendencia creciente entre 1990 y 2001. Conclusiones La mortalidad por DM afecta principalmente a personas mayores de 50 años y a hombres. Es significativa la tendencia decreciente en las tasas ajustadas de mortalidad por DM para mujeres. Se subraya la importancia de desarrollar políticas de prevención y de detección temprana, como así también la codificación de la muerte por múltiples causas.

ABSTRACT Objectives To describe the time trend of mortality attributable to diabetes mellitus (DM) in Argentina in the years 1990-2013, by age and sex. Methods Crude, age-specific, and age-adjusted rates of DM mortality in Argentina were calculated for the period 1990-2013. Mortality data were obtained from the Statistical Report on Deaths issued by the Department of Statistics and Health Information. An analysis of this trend was carried out through joinpoint regression models. Results Analysis of the trend of crude and age-adjusted DM mortality rates yielded a statistically significant model in which mortality increased between 1990 and 2001 and declined thereafter. Furthermore, for age-adjusted rates, there was a significant downward trend of mortality in women (AAPC -1.10, 95%CI -1.70 to -0.50). Age-specific mortality rates multiplied with every 10-year increment in age. All age groups older than 50 years showed a growing mortality trend between 1990 and 2001. Conclusions DM mortality mainly affects people over the age of 50 and men. A significant downward trend in age-adjusted DM mortality rates was observed for women. These findings highlight the importance of developing policies for prevention and early detection, as well as of proper coding of multiple causes of death.

RESUMO Objetivos Descrever a tendência temporal da mortalidade por diabetes mellitus (DM) na Argentina no período entre 1990 e 2013, por idade e sexo. Métodos Foram estimados os índices de mortalidade por DM brutos por idade e ajustados por idade na Argentina para o período 1990–2013. Os dados de mortalidade foram obtidos do Relatório estatístico de óbitos elaborado pelo Núcleo de Estatísticas e Informação em Saúde. Foi realizada uma análise da tendência com o uso de modelos de regressão por joinpoint. Resultados A análise da tendência dos índices de mortalidade por DM brutos e ajustados por idade indica um modelo estatisticamente significativo com aumento da mortalidade entre 1990 e 2001, ponto a partir do qual é observado um declínio. Com relação aos índices ajustados por idade, verifica-se uma tendência significativa de declínio da mortalidade no sexo feminino (AAPC: –1,10, IC 95%: –1,70; –0,50). Os índices de mortalidade por idade são multiplicados a cada 10 anos de idade. Verifica-se uma tendência crescente em todas as faixas etárias acima de 50 anos entre 1990 e 2001. Conclusões A mortalidade por DM atinge principalmente indivíduos do sexo masculino e com idade acima de 50 anos. É significativa a tendência decrescente nos índices de mortalidade por DM ajustados no sexo feminino. Destaca-se a importância de desenvolver políticas de prevenção e detecção precoce e da codificação dos óbitos por múltiplas causas.

Global long interspersed nuclear element 1 DNA methylation in a Colombian sample of patients with late-onset Alzheimer's disease.

Alterations in DNA methylation have implicated as an epigenetic event in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this work was to evaluate global DNA methylation levels for long interspersed nuclear element 1 (LINE-1) repetitive sequences in Colombian patients with LOAD and controls. The LINE-1 DNA methylation levels in peripheral blood samples from 28 Colombian patients with LOAD and 30 healthy participants were assessed using a methylation-sensitive high-resolution melting (MS-HRM) quantitative assay. We did not find differences in LINE-1 methylation levels between patients with Alzheimer's disease (AD; median 76.2%, interquartile range [IQR]: 69.8-81.9) and control participants (median 79.8%, IQR: 73.2-83.8; P = .3). Additional stratified analyses did not show differences in LINE-1 methylation levels for male or female patients versus controls nor for apolipoprotein E4 carriers and noncarriers. This is the first report of LINE-1 methylation levels in patients with LOAD using the cost-effective MS-HRM technique, and this is the first global DNA methylation study in Latin American patients with AD.