Sodium Tungstate (NaW) Decreases Inflammation and Renal Fibrosis in Diabetic Nephropathy.

BACKGROUND: Diabetic Nephropathy is one of the most severe complications of Diabetes Mellitus and the main cause of end-stage kidney disease worldwide. Despite the therapies available to control blood glucose and blood pressure, many patients continue to suffer from progressive kidney damage. Chronic hyperglycemia is the main driver of changes observed in diabetes; however, it was recently discovered that inflammation and oxidative stress contribute to the development and progression of kidney damage. Therefore, it is important to search for new pharmacological therapies that stop the progression of DN. Sodium tungstate (NaW) is an effective short and long-term antidiabetic agent in both type 1 and type 2 diabetes models. METHODS: In this study, the effect of NaW on proinflammatory signalling pathways, proinflammatory proteins and fibrosis in the streptozotocin (STZ)-induced type 1 diabetic rat model was analysed using histological analysis, western blotting and immunohistochemistry. RESULTS: NaW treatment in diabetic rats normalize parameters such as glycemia, glucosuria, albuminuria/creatinuria, glomerular damage, and tubulointerstitial damage. NaW decreased the proinflammatory signaling pathway NF-κB, inflammatory markers (ICAM-1, MCP-1 and OPN), profibrotic pathways (TGFß1/Smad2/3), reduced epithelial-mesenchymal transition (α -SMA), and decreased renal fibrosis (type IV collagen). CONCLUSION: NaW could be an effective drug therapy for treating human diabetic nephropathy.

Ethnic differences in disability-free life expectancy and disabled life expectancy in older adults in Chile.

BACKGROUND: Although about 10% of the Latin American population is indigenous, ethnic differences in disability-free life expectancy (DFLE) and life expectancy with disability (DLE) are unknown. OBJECTIVE: To estimate disability-free life expectancy and disabled life expectancy among Mapuche (the largest indigenous group) and non-indigenous older adults aged 60 years or more in Chile. METHOD: Disability was measured following a methodology that combines limitations of daily living, cognitive impairment and dependence previously validated in Chile. Finally, the DFLE was estimated using Sullivan's method combining life tables by ethnicity and disability proportions from the EDES survey designed for the study of ethnic differentials in health and longevity in Chile. RESULTS: Non-Indigenous people have a higher total and Disability-free life expectancy compared to Mapuche people at all ages. While at age 60 a Mapuche expects to live 18.9 years, of which 9.4 are disability-free, a non-Indigenous expects to live 26.4 years, of which 14 are disability-free. In addition, although the length of life with disability increases with age for both populations, Mapuche who survive to age 80 or 90 expect to live 84% and 91% of their remaining life with disability, higher proportions compared to non-indigenous people (62.9% and 75%, respectively). CONCLUSIONS: This is the first study addressing inequities in DFLE between the Mapuche and non-Indigenous population, reflected in lower total life expectancy, lower DFLE and higher DLE in Mapuche compared to the non-Indigenous population. Our results underscore the need for increased capacity to monitor mortality risks among older people, considering ethnic differences.

Índice de riesgo de obesidad infantil (IROBIC) para áreas administrativas pequeñas en Chile / Childhood obesity risk index (IROBIC) for small administrative areas in Chile

Introducción: a pesar de la alta prevalencia de la obesidad infantil (OI) globalmente, no existen índices compuestos para estimar los aspectos territoriales asociados al riesgo de OI. Objetivo: elaborar un índice de riesgo de OI (IROBIC) para unidades administrativas pequeñas (comunas) de Chile Métodos: se utilizaron datos de 2019 de fuentes públicas con información de menores de 10 años de todas las comunas de las 2 regiones más grandes. El IROBIC incluye 16 indicadores estandarizados por comuna y agrupados en cuatro dimensiones, determinadas por análisis de componentes principales (salud, socio económica, entornos comunal y educacional). Se determinó el IROBIC mediante una media geométrica ponderada y posteriormente se calcularon las diferencias entre las 10 y 5 comunas con mayores y menores IROBIC y de cada dimensión, con el coeficiente de disparidad Resultados: aun cuando los mayores IROBIC se obtuvieran en comunas más vulnerables, su valor total y el de cada dimensión, mostraron que es posible amortiguar los efectos de la desigualdad sobre la OI. Las 10 y 5 comunas con mayor IROBIC presentan un riesgo, 2,41 y 4,05 veces mayor que las de menor valor, respectivamente. Conclusiones: el IROBIC puede monitorear el riesgo de OI —y factores asociados— desde una perspectiva territorial. (AU)

Introduction: although the prevalence of childhood obesity (CO) is high globally, there are no composite indices to estimate territorial aspects associated with its risk Objective: to develop an obesity risk index (IROBIC) for small administrative units, called “comunas” in Chile Methods: we used 2019 data from public sources on children under 10 years living in “comunas” of the two largest regions. IROBIC includes 16 indicators standardized for each “comuna” and grouped together into four domains, determined by principal component analysis (health, socio-economic, built-in and educational environments). IROBIC was calculated as a weighted geometric mean. Differences in obesity risk between the 10 and 5 “comunas” with the highest and lowest IROBIC and of each domain, were calculated with the disparity ratio. Results: in spite of the poorest “comunas” having the highest IROBIC, when its value and that for each domain were considered, we observed that the effect of inequality could be mitigated. The 10 and 5 “comunas” with the highest IROBIC have a 2.41 and 4.05 higher risk of CO compared to those with the lowest values Conclusions: IROBIC is a useful tool for monitoring the risk of CO and its factors from a territorial perspective. (AU)

Life expectancy by ethnic origin in Chile.

Background: Ethnic and racial differences in life expectancy have been well established in different societies. However, even though an important part of the population of Latin America is Indigenous, there is little knowledge about them. Objective: Determine if there are ethnic differences in life expectancy at birth and at 60 years in Chile, and if the Mapuche (largest Indigenous ethnic group) have similar life expectancy to other Indigenous peoples. Method: Life tables for the Mapuche and other Indigenous groups and non-Indigenous people were built using the 2017 census. Specifically, we used the questions of the number of live children born and the number of surviving children. With this information, using the indirect method of own children we determined infantile mortality. Then, using the relational logit model and the model life table (west), we estimated the survival function for all ages. Results: Indigenous Chileans have seven years lower life expectancy at birth than the non-Indigenous population (76.2 vs. 83.2 years). The differential at age 60 is 6 years (20.3 vs. 26.4 years). We also found that Mapuche have an even greater disadvantage in survival than other ethnic groups. This is reflected in 2 years less life expectancy, both at birth and at 60 years. Discussion: Our results ratify the existence of marked ethnic-racial inequality in the extension of life in Chile and demonstrate a greater disadvantage in terms of survival of the Mapuche compared to other Indigenous and non-Indigenous groups. It is thus of great relevance to design policies that would decrease the existing inequalities in lifespan.

Epigenetic reprogramming around IFN1 and IFNy2 promoters in rainbow trout cells inoculated with infectious pancreatic necrosis virus (IPNV).

Infectious pancreatic necrosis virus (IPNV) has proven to effectively evade the host antiviral responses. This study clarifies whether the modulation of the antiviral immune response exerted by IPNV involves epigenetic mechanisms. An in-silico characterization of the rainbow trout IFN1 and IFNγ2 promoters was performed, identifying the islands or sequences rich in CpG dinucleotides and the putative transcription factor binding sites (TBS) for both gene promoters. RTS11 cells (rainbow trout monocyte/macrophage) were infected with IPNV, and the course of viral infection was followed up to 48 h post infection (hpi). Infected cells showed increased IFN1 and IFNγ2 transcriptional expression at 6 and 24 hpi, respectively. IPNV infection caused increases and decreases in global IFNγ2 promoter methylation at 6 and 24 hpi, respectively. The CpG dinucleotides at positions -392 and + 38 of this promoter were the most sensitive to methylation changes. The IFN1 promoter remained fully unmethylated during the course of the infection, similar to the control. The changes in the methylation pattern observed for the IFNγ2 promoter were coincident with the changes in DNA methyltransferase (DNMT) expression levels, increasing at 6 hpi and decreasing below basal level at 24 hpi. Similarly, the H4 histones associated with the IFN1 and IFNγ2 promoters were hyperacetylated at 6 hpi, subsequently decreasing their acetylation below basal levels at 24 hpi, in both promoters. Coincidentally with the above, overexpression of histone acetyltransferase (HAT) was observed at 6 hpi and of histone deacetylase (HDAC) at 24 hpi, with return to baseline of HAT. These results suggest that IPNV would epigenetically modulate the expression of IFN1 by changing acetylation levels of the histones H4 associated with its promoter. Also, the modulation of the expression of IFNy2 would be by switching methylation/demethylation levels of its promoter, in addition to changes in acetylation levels of histones H4 associated with this promoter. This study is the first to demonstrate the effect of epigenetic reprogramming after IPNV infection in salmonid cells, demonstrating that promoter methylation/demethylation level and changes in the histone code associated with promoters may play a role in the modulation of the immune response induced by the virus.

[Childhood obesity risk index (IROBIC) for small administrative areas in Chile]. / Índice de riesgo de obesidad infantil (IROBIC) para áreas administrativas pequeñas en Chile.

Introduction: Introduction: although the prevalence of childhood obesity (CO) is high globally, there are no composite indices to estimate territorial aspects associated with its risk Objective: to develop an obesity risk index (IROBIC) for small administrative units, called "comunas" in Chile Methods: we used 2019 data from public sources on children under 10 years living in "comunas" of the two largest regions. IROBIC includes 16 indicators standardized for each "comuna" and grouped together into four domains, determined by principal component analysis (health, socio-economic, built-in and educational environments). IROBIC was calculated as a weighted geometric mean. Differences in obesity risk between the 10 and 5 "comunas" with the highest and lowest IROBIC and of each domain, were calculated with the disparity ratio. Results: in spite of the poorest "comunas" having the highest IROBIC, when its value and that for each domain were considered, we observed that the effect of inequality could be mitigated. The 10 and 5 "comunas" with the highest IROBIC have a 2.41 and 4.05 higher risk of CO compared to those with the lowest values Conclusions: IROBIC is a useful tool for monitoring the risk of CO and its factors from a territorial perspective.

Introducción: Introducción: a pesar de la alta prevalencia de la obesidad infantil (OI) globalmente, no existen índices compuestos para estimar los aspectos territoriales asociados al riesgo de OI. Objetivo: elaborar un índice de riesgo de OI (IROBIC) para unidades administrativas pequeñas (comunas) de Chile Métodos: se utilizaron datos de 2019 de fuentes públicas con información de menores de 10 años de todas las comunas de las 2 regiones más grandes. El IROBIC incluye 16 indicadores estandarizados por comuna y agrupados en cuatro dimensiones, determinadas por análisis de componentes principales (salud, socio económica, entornos comunal y educacional). Se determinó el IROBIC mediante una media geométrica ponderada y posteriormente se calcularon las diferencias entre las 10 y 5 comunas con mayores y menores IROBIC y de cada dimensión, con el coeficiente de disparidad Resultados: aun cuando los mayores IROBIC se obtuvieran en comunas más vulnerables, su valor total y el de cada dimensión, mostraron que es posible amortiguar los efectos de la desigualdad sobre la OI. Las 10 y 5 comunas con mayor IROBIC presentan un riesgo, 2,41 y 4,05 veces mayor que las de menor valor, respectivamente. Conclusiones: el IROBIC puede monitorear el riesgo de OI ­y factores asociados­ desde una perspectiva territorial.

Socio-Spatial Segregation of Unhealthy Food Environments across Public Schools in Santiago, Chile.

Santiago, Chile is a very segregated city, with higher childhood obesity rates observed in vulnerable areas. We compared the counts and proximity of unhealthy food outlets (UFOs) around a 400 m buffer of 443 public schools (municipal and subsidized) located in socioeconomically diverse neighborhoods in 14 municipalities of Santiago. This was a cross-sectional study in which the socioeconomic status (SES) of the population living inside the buffer was classified as middle-high, middle, and low. We used the Kruskal-Wallis test for comparisons of density and proximity between type of school, SES, and population density. We used a negative binomial model (unadjusted and adjusted by population density) to determine the expected change in counts of UFOs by SES, which was compared to the reference (middle-high). Low SES neighborhoods had significantly more counts of UFOs, and these were located much closer to schools. Low and middle SES neighborhoods had an 88% and 48% higher relative risk of having UFOs compared to middle-high SES areas; (IRR = 1.88; 95% CI 1.59-2.23) and (IRR = 1.48; 95% CI 1.20-1.82), respectively. A socio-spatial segregation of UFOs associated with childhood obesity across public schools was observed in Santiago.

Marital Status, Living Arrangements and Mortality at Older Ages in Chile, 2004-2016.

The risk of mortality in old age is associated with marital status and living arrangements. There is still little knowledge about this in Latin America. Our objectives are to examine the association between marital status, living arrangements and mortality of older adults (>60 years) in Chile, and to test whether this association varies when demographic, socioeconomic and health factors are included. We used data from the Social Protection Survey, and mortality data were linked to the Civil Registry. We estimate a series of Poisson regression models. Our results show a clear association between marriage and longevity, since even controlling for demographic, socioeconomic and health factors, we found that separated or divorced, widowed, and unmarried people showed higher relative mortality compared to married people (IRR1.24, IRR1.33, IRR1.35, respectively). Considering only living arrangements, the results show that living alone, alone with children, with children and other relatives or in other arrangements is associated with higher mortality (IRR1.22, IRR1.27, IRR1.35, IRR1.35, respectively) compared to those living with their partners and children. However, considering marital status and living arrangements together, we find that survival among older adults was strongly associated with marital status. Marital status continues to be a direct measure of living arrangements among older adults in Chile.

Social participation and 5-year all-cause mortality in older Chilean people.

We aimed to examine the degree to which social participation is associated with mortality risk in older adults in Chile. We used the Chilean National Survey on Elderly Dependency, which is linked to vital statistics, in order to obtain death records. Four proportional risk regression models were estimated. Even with controlled sociodemographic, economic, family, and health variables, older adults who participate in social activities had a 22% lower risk of death than those who do not participate. We concluded that social participation is a strong and significant protective factor for mortality in Chilean older adults. Social participation should thus be promoted from a life course perspective considering its effect on mortality in older adults who maintained an active social life.

The Importance of Education for Middle- and Old-Age Mortality in Chile: Estimates From Panel Data Linked to Death Records.

OBJECTIVES: To examine the association between education and mortality by age and gender in Chile. METHODS: We drew data from 10,147 adults aged 40 years and over from the Chilean Social Protection Survey linked to the national death records. We specify five Cox regression models to estimate the main and interaction effects for education levels, age, sex, and mortality. RESULTS: The hazard ratios reduce with increasing education. Secondary and tertiary education levels are associated, respectively, with 34% and 41% lower hazard rates than 0-4 years of schooling. Also, the educational gradient in mortality is significantly weaker at older ages, and it does not differ by gender. DISCUSSION: Our findings endorse the negative association of formal education with adult mortality, uncovering Chile's structural problems despite the economic improvements underway. It also corroborates the importance of novel longitudinal data for mortality analyses in Latin America.

Migração dos médicos: uma análise dos movimentos migratórios dos profissionais da saúde no Brasil segundo Unidades de Federação (2000-2010) / Migration of physicians: an analysis of the migratory movements of health professionals in Brazil according to Federation Units (2000-2010)

O objetivo do trabalho é identificar os principais padrões migratórios dos profissionais médicos segundo as Unidades de Federação (UFs) do Brasil, a partir dos Censos Demográficos dos anos 2000 e 2010. Construíram-se matrizes de migração para cada um dos pontos do tempo e se estimam taxas liquidas de migração para cada UF. Os resultados mostram que, apesar da identificação de um aumento no número de médicos que migram para outras UFs durante o período de estudo, continuam existindo diferenças significativas entre as regionais e UFs, em relação à alocação de médicos. A região Sudeste, especificamente, São Paulo, Minas Gerais e Rio de Janeiro são as principais UFs, fornecedoras de médicos para outros Estados e também são as principais receptoras. Realidade oposta é a de Amapá, a UF que recebe a menor quantidade de médicos imigrantes. Acreditamos que os resultados desta natureza permitem que o conhecimento sobre os deslocamentos dos médicos contribua a melhorar desenhos de planos estratégicos para estabelecer a quantidade mínima de médicos que cada Unidade de Federação do Brasil possa ter e monitorar estas correntes migratórias de mão de obra tão qualificada e específica como são os médicos.

The aim of this study is to identify the main migration patterns of medical professionals according to the Brazilian Federative Units (UFs), based on Demographic Census data of the years 2000 and 2010. Migration matrices for each of point in time are produced, and net migration rates for each UF are estimated. The results show that despite the increase in the number of physicians out flowing to other UFs during the study period, there are still significant differences between Regions and UFs related to the allocation of physicians. The Southeast Region, particularly, São Paulo, Minas Gerais and Rio de Janeiro are the main UFs providing these professionals to other states and are also the main attractors. Amapá shows opposite reality: it is the UF that receives the lowest inflow of physicians. Results suggest that the sort of knowledge presented about spatial movements of physicians may contribute to the design of strategic plans that allow each Federation Units of Brazil count on a minimum quantity of physicians. It is also am important tool for monitoring in-outflows of highly qualified and specific labor force as the physicians are.

Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom complexity, effects of captivity, sexual dimorphism, differences among species.

A characteristic of venom elution patterns, shared with many other complex systems, is that many their features cannot be properly described with statistical or euclidean concepts. The understanding of such systems became possible with Mandelbrot's fractal analysis. Venom elution patterns were produced using the reversed phase high performance liquid chromatography (HPLC) with 1 mg of venom. One reason for the lack of quantitative analyses of the sources of venom variability is parametrizing the venom chromatograms' complexity. We quantize this complexity by means of an algorithm which estimates the contortedness (Q) of a waveform. Fractal analysis was used to compare venoms and to measure inter- and intra-specific venom variability. We studied variations in venom complexity derived from gender, seasonal and environmental factors, duration of captivity in the laboratory, technique used to milk venom.

Extracellular pH in restricted domains as a gating signal for ion channels involved in transepithelial transport.

The importance of intracellular pH (pH(i)) in the regulation of diverse cellular activities ranging from cell proliferation and differentiation to cell cycle, migration and apoptosis has long been recognised. More recently, extracellular pH (pH0), in particular that of relatively inaccessible compartments or domains that occur between cells in tissues, has begun to be acknowledged as a relevant signal in cell regulation. This should not be surprising given the abundant reports highlighting the pH0-dependence of the activity of membrane proteins facing the extracellular space such as receptors, transporters, ion channels and enzymes. Changes in pH affect the ionisation state of proteins through the effect on their titratable groups. There are proteins, however, which respond to pH shifts with conformational changes that are crucial for catalysis or transport activity. In such cases protons act as signalling molecules capable of eliciting fast and localised responses. We provide examples of ion channels that appear fastidiously designed to respond to extracellular pH in a manner that suggests specific functions in transporting epithelia. We shall also present ideas as to how these channels participate in complex transepithelial transport processes and provide preliminary experiments illustrating a new way to gauge pH0 in confined spaces of native epithelial tissue.

A genetically encoded ratiometric sensor to measure extracellular pH in microdomains bounded by basolateral membranes of epithelial cells.

Extracellular pH, especially in relatively inaccessible microdomains between cells, affects transport membrane protein activity and might have an intercellular signaling role. We have developed a genetically encoded extracellular pH sensor capable of detecting pH changes in basolateral spaces of epithelial cells. It consists of a chimerical membrane protein displaying concatenated enhanced variants of cyan fluorescence protein (ECFP) and yellow fluorescence protein (EYFP) at the external aspect of the cell surface. The construct, termed pHCECSensor01, was targeted to basolateral membranes of Madin-Darby canine kidney (MDCK) cells by means of a sequence derived from the aquaporin AQP4. The fusion of pH-sensitive EYFP with pH-insensitive ECFP allows ratiometric pH measurements. The titration curve of pHCECSensor01 in vivo had a pK (a) value of 6.5 +/- 0.04. Only minor effects of extracellular chloride on pHCECSensor01 were observed around the physiological concentrations of this anion. In MDCK cells, the sensor was able to detect changes in pH secondary to H(+) efflux into the basolateral spaces elicited by an ammonium prepulse or lactate load. This genetically encoded sensor has the potential to serve as a noninvasive tool for monitoring changes in extracellular pH microdomains in epithelial and other tissues in vivo.

Adaptação do método das componentes demográficas na estimação do número de médicos: aplicação comparativa em estados selecionados do Brasil, 2010-2030¹ / Adaptation of the demographic components method to estimate the number of doctors: comparative application in selected states in Brazil, 2010-2030¹

Trabalho essencialmente metodológico que estima o número de médicos (2010-2030), mediante a adequação do método das componentes demográficas incorporando informação sobre migração específica de médicos. Esta é susceptível de ser modelada em cenários que incorporem (ou traduzam) planos diretores visando quantificação da oferta de médicos, de forma que seja possível ter projeções normativas. Os volumes da mão de obra médica obtidos nestas simulações somente serão alcançados num cenário generalizado de ampliação sustentada da oferta de novas vagas para a formação de médicos. Se expansões desta magnitude são impossíveis de manter por um longo prazo, como estes resultados sugerem, resta ao Sistema se adequar à escassez estrutural e crônica de médicos se reorganizando para otimizar o estoque de médicos que –de acordo a estas simulações–dificilmente reproduzirão situações semelhantes às de contextos desenvolvidos.