Relationship between body mass index and residential segregation in large cities of Latin America.

BACKGROUND: Obesity is a global health problem, and its connection with social and environmental factors is well-established. Social factors, such as urban segregation, may impact obesity through various mechanisms, including food and physical activity environments, as well as social norms and networks. This multilevel study aims to examine the effect of socio-economic residential segregation of Latin American cities on the obesity of individuals within those cities. METHODS: We analyzed data from national surveys for a total of 59,340 individuals of 18-70 years of age, conducted in 156 cities across Brazil, Chile, Colombia, and Mexico between 2007 and 2013. We adjusted two-level linear mixed models for body mass index (BMI) stratified by sex and country, controlling for age, educational level and poverty. Separate models were built for dissimilarity and isolation segregation indices. RESULTS: The relationships between segregation indices and BMI were mostly not statistically significant, and in some cases, they were opposite to what was expected. The only significant relationships were observed in Colombian men, using the dissimilarity index (-7.5 [95% CI: -14.4, -0.5]) and in Colombian women, using the isolation index (-7.9 [95% CI: -14.1, -1.7]). CONCLUSIONS: While individual-level factors cannot fully explain differences among people in the same city, segregation indices may help. However, we found that in some cases, the relationship between BMI and segregation indices is opposite to what is expected based on prior literature. This should be considered in examining the phenomenon. Further research on obesogenic environments in segregated neighborhoods could provide valuable evidence.

Nowcasting methods to improve the performance of respiratory sentinel surveillance: lessons from the COVID-19 pandemic.

Respiratory diseases, including influenza and coronaviruses, pose recurrent global threats. This study delves into the respiratory surveillance systems, focusing on the effectiveness of SARI sentinel surveillance for total and severe cases incidence estimation. Leveraging data from the COVID-19 pandemic in Chile, we examined 2020-2023 data (a 159-week period) comparing census surveillance results of confirmed cases and hospitalizations, with sentinel surveillance. Our analyses revealed a consistent underestimation of total cases and an overestimation of severe cases of sentinel surveillance. To address these limitations, we introduce a nowcasting model, improving the precision and accuracy of incidence estimates. Furthermore, the integration of genomic surveillance data significantly enhances model predictions. While our findings are primarily focused on COVID-19, they have implications for respiratory virus surveillance and early detection of respiratory epidemics. The nowcasting model offers real-time insights into an outbreak for public health decision-making, using the same surveillance data that is routinely collected. This approach enhances preparedness for emerging respiratory diseases by the development of practical solutions with applications in public health.

Orai1α and Orai1ß support calcium entry and mammosphere formation in breast cancer stem cells.

Orai1 is the pore-forming subunit of the Ca2+-release activated Ca2+ channels that mediate store-operated Ca2+ entry (SOCE) in excitable and non-excitable cells. Two Orai1 forms have been identified in mammalian cells, the full-length variant Orai1α, and the short form Orai1ß, lacking the N-terminal 63 amino acids. Stem cells were isolated from non-tumoral breast epithelial cells of the MCF10A cell line, and the most representative ER+ , HER2 or triple negative breast cancer cell lines MCF7, SKBR3 and MDA-MB-231, respectively. Orai and TRPC family members expression was detected by RT-PCR and Western blotting. Changes in cytosolic Ca2+ concentration were analyzed by confocal microscopy using Fluo 4 and the spheroid-forming ability and self-renewal was estimated in culture plates coated with pHEMA using a cell imaging system. Here, we have characterized the expression of Orai family members and several TRPC channels at the transcript level in breast stem cells (BSC) derived from the non-tumoral breast epithelial cell line MCF10A and breast cancer stem cells (BCSC) derived from the well-known estrogen receptor positive (ER+), HER2 and triple negative cell lines MCF7, SKBR3 and MDA-MB-231, respectively. Furthermore, we have evaluated the mammosphere formation efficiency and self-renewal of the BSC and BCSC. Next, through a combination of Orai1 knockdown by iRNA and the use of MDA-MB-231 KO cells, missing the native Orai1, transfected with plasmids encoding for either Orai1α or Orai1ß, we show that Orai1 is essential for mammosphere formation and self-renewal efficiency in BCSC derived from triple negative and HER2 subtypes cell cultures, while this channel has a negligible effect in BCSC derived from ER+ cells as well as in non-tumoral BSC. Both, Orai1α, and Orai1ß support SOCE in MDA-MB-231-derived BCSC with similar efficiency, as well as COX activation and mammosphere formation. These findings provide evidence of the functional role of Orai1α and Orai1ß in spheroid forming efficiency and self-renewal in breast cancer stem cells.

Functional differences in agonist-induced plasma membrane expression of Orai1α and Orai1ß.

Orai1 is the pore-forming subunit of the store-operated Ca2+ release-activated Ca2+ (CRAC) channels involved in a variety of cellular functions. Two Orai1 variants have been identified, the long form, Orai1α, containing 301 amino acids, and the short form, Orai1ß, which arises from alternative translation initiation from methionines 64 or 71, in Orai1α. Orai1 is mostly expressed in the plasma membrane, but a subset of Orai1 is located in intracellular compartments. Here we show that Ca2+ store depletion leads to trafficking and insertion of compartmentalized Orai1α in the plasma membrane via a mechanism that is independent on changes in cytosolic free-Ca2+ concentration, as demonstrated by cell loading with the fast intracellular Ca2+ chelator dimethyl BAPTA in the absence of extracellular Ca2+ . Interestingly, thapsigargin (TG) was found to be unable to induce translocation of Orai1ß to the plasma membrane when expressed individually; by contrast, when Orai1ß is co-expressed with Orai1α, cell treatment with TG induced rapid trafficking and insertion of compartmentalized Orai1ß in the plasma membrane. Translocation of Orai1 forms to the plasma membrane was found to require the integrity of the actin cytoskeleton. Finally, expression of a dominant negative mutant of the small GTPase ARF6, and ARF6-T27N, abolished the translocation of compartmentalized Orai1 variants to the plasma membrane upon store depletion. These findings provide new insights into the mechanism that regulate the plasma membrane abundance of Orai1 variants after Ca2+ store depletion.

Cancer Care Access in Chile's Vulnerable Populations During the COVID-19 Pandemic.

Objectives. To examine the COVID-19 pandemic's impact on cancer care access in Chile, analyzing differential effects by insurance type, gender, and age. Methods. We conducted a quasi-experimental study using interrupted time series analysis. We used multiple data sources for a broad evaluation of cancer-related health care utilization from January 2017 to December 2020. We fit negative binomial models by population groups for a range of services and diagnoses. Results. A sharp drop in oncology health care utilization in March was followed by a slow, incomplete recovery over 2020. Cumulative cancer-related services, diagnostic confirmations, and sick leaves were reduced by one third in 2020; the decrease was more pronounced among women and the publicly insured. Early diagnosis was missed in 5132 persons with 4 common cancers. Conclusions. The pandemic stressed the Chilean health system, decreasing access to essential services, with a profound impact on cancer care. Oncology service reductions preceded large-scale lockdowns and supply-side disruptions. Importantly, not all population groups were equally affected, with patterns suggesting that gender and socioeconomic inequalities were exacerbated. (Am J Public Health. 2022;112(S6):S591-S601. https://doi.org/10.2105/AJPH.2021.306587).

[Cancer care access in Chile's vulnerable populations during the COVID-19 pandemicAcesso a tratamento de câncer em populações vulneráveis no Chile durante a pandemia de COVID-19]. / Acceso a la atención del cáncer en los grupos vulnerables de Chile durante la pandemia de COVID-19.

Objectives: To examine the COVID-19 pandemic's impact on cancer care access in Chile, analyzing differential effects by insurance type, gender, and age. Methods: We conducted a quasi-experimental study using interrupted time series analysis. We used multiple data sources for a broad evaluation of cancer-related health care utilization from January 2017 to December 2020. We fit negative binomial models by population groups for a range of services and diagnoses. Results: A sharp drop in oncology health care utilization in March was followed by a slow, incomplete recovery over 2020. Cumulative cancer-related services, diagnostic confirmations, and sick leaves were reduced by one third in 2020; the decrease was more pronounced among women and the publicly insured. Early diagnosis was missed in 5132 persons with 4 common cancers. Conclusions: The pandemic stressed the Chilean health system, decreasing access to essential services, with a profound impact on cancer care. Oncology service reductions preceded large-scale lockdowns and supply-side disruptions. Importantly, not all population groups were equally affected, with patterns suggesting that gender and socioeconomic inequalities were exacerbated.

Objetivos: Examinar o impacto da pandemia de COVID-19 no acesso a tratamento de câncer no Chile, analisando efeitos diferenciais por tipo de cobertura de assistência à saúde, gênero e idade. Métodos: Realizamos um estudo quase-experimental utilizando análise de séries temporais interrompidas. A partir de várias fontes de dados, efetuamos uma avaliação abrangente da utilização de atenção à saúde relacionada ao câncer, de janeiro de 2017 a dezembro de 2020. Ajustamos modelos binomiais negativos por grupos populacionais a vários tipos de serviços e diagnósticos. Resultados: Uma queda acentuada no uso da assistência médica oncológica em março foi seguida por uma recuperação lenta e incompleta ao longo de 2020. Cumulativamente, a utilização de serviços oncológicos, as confirmações de diagnóstico e os afastamentos do trabalho por doença foram reduzidos em um terço em 2020. Essa redução foi mais pronunciada em mulheres e usuários do sistema público de saúde. No total, 5132 pessoas com 4 cânceres comuns não foram diagnosticadas precocemente. Conclusões: A pandemia impôs pressão sobre o sistema de saúde chileno, reduzindo o acesso a serviços essenciais e causando um profundo impacto no tratamento do câncer. As reduções na prestação de serviços de oncologia precederam os lockdowns em larga escala e as interrupções na oferta de suprimentos. É importante ressaltar que nem todos os grupos populacionais foram igualmente afetados e os padrões observados sugerem que as desigualdades de gênero e socioeconômicas foram exacerbadas.

Aging and self-reported health in 114 Latin American cities: gender and socio-economic inequalities.

BACKGROUND: Understanding how urban environments influence people's health, especially as individuals age, can help identify ways to improve health in the rapidly urbanizing and rapidly aging populations. OBJECTIVES: To investigate the association between age and self-reported health (SRH) in adults living in Latin-American cities and whether gender and city-level socioeconomic characteristics modify this association. METHODS: Cross-sectional analyses of 71,541 adults aged 25-97 years, from 114 cities in 6 countries (Argentina, Brazil, Colombia, Chile, El Salvador, and Guatemala), as part of the Salud Urbana en America Latina (SALURBAL) Project. We used individual-level age, gender, education, and self-reported health (SRH) data from harmonized health surveys. As proxies for socioeconomic environment we used a city-level socioeconomic index (SEI) calculated from census data, and gross domestic product (GDP) per-capita. Multilevel Poisson models with a robust variance were used to estimate relative risks (RR), with individuals nested in cities and binary SRH (poor SHR vs. good SRH) as the outcome. We examined effect modification by gender and city-level socioeconomic indicators. RESULTS: Overall, 31.4% of the sample reported poor SRH. After adjusting for individual-level education, men had a lower risk of poor SRH (RR = 0.76; CI 0.73-0.78) compared to women, and gender modified the association between age and poor SRH (p-value of interaction < 0.001). In gender stratified models, the association between older age and poor SRH was more pronounced in men than in women, and in those aged 25-65 than among those 65+ (RR/10 years = 1.38 vs. 1.10 for men, and RR/10 years = 1.29 vs. 1.02 for women). Living in cities with higher SEI or higher GDP per-capita was associated with a lower risk of poor SRH. GDP per-capita modified the association between age (25-65) and SRH in men and women, with SEI the interaction was less clear. CONCLUSIONS: Across cities in Latin America, aging impact on health is significant among middle-aged adults, and among men. In both genders, cities with lower SEI or lower GDP per-capita were associated with poor SRH. More research is needed to better understand gender inequalities and how city socioeconomic environments, represented by different indicators, modify exposures and vulnerabilities associated with aging.

Acceso a la atención del cáncer en los grupos vulnerables de Chile durante la pandemia de COVID-19

[RESUMEN]. Objetivo. Estudiar la repercusión de la pandemia de COVID-19 en el acceso a la atención del cáncer en Chile, analizando los efectos diferenciales por tipo de seguro, sexo y edad. Métodos. Se llevó a cabo un estudio cuasiexperimental mediante análisis de series temporales interrumpi- das. Se recurrió a fuentes de datos múltiples con el fin de lograr una evaluación amplia de la utilización de la atención del cáncer de enero del 2017 a diciembre del 2020. Se ajustaron modelos binomiales negativos en función de los grupos de población para una diversidad de servicios y diagnósticos. Resultados. Tras una disminución considerable de la utilización de la atención oncológica en marzo, se observó una recuperación lenta e incompleta durante el 2020. Los servicios de atención del cáncer, las con- firmaciones diagnósticas y las licencias por enfermedad acumulados se redujeron en un tercio en el 2020; la disminución fue más pronunciada en las mujeres y las personas afiliadas al seguro de enfermedad público. No se hizo un diagnóstico temprano en 5132 personas con cuatro tipos frecuentes de cáncer. Conclusiones. La pandemia sobrecargó el sistema de salud chileno y provocó una disminución del acceso a los servicios básicos, con una repercusión profunda en la atención del cáncer. La reducción de los servicios de oncología precedió los confinamientos a gran escala y las interrupciones por parte de los prestadores. Cabe destacar que no todos los grupos de la población se vieron afectados por igual y se observaron pautas que indican un agravamiento de las desigualdades por situación socioeconómica y sexo.

[ABSTRACT]. Objectives. To examine the COVID-19 pandemic’s impact on cancer care access in Chile, analyzing differential effects by insurance type, gender, and age. Methods. We conducted a quasi-experimental study using interrupted time series analysis. We used multiple data sources for a broad evaluation of cancer-related health care utilization from January 2017 to December 2020. We fit negative binomial models by population groups for a range of services and diagnoses. Results. A sharp drop in oncology health care utilization in March was followed by a slow, incomplete recovery over 2020. Cumulative cancer-related services, diagnostic confirmations, and sick leaves were reduced by one third in 2020; the decrease was more pronounced among women and the publicly insured. Early diagnosis was missed in 5132 persons with 4 common cancers. Conclusions. The pandemic stressed the Chilean health system, decreasing access to essential services, with a profound impact on cancer care. Oncology service reductions preceded large-scale lockdowns and supply-side disruptions. Importantly, not all population groups were equally affected, with patterns suggesting that gender and socioeconomic inequalities were exacerbated.

[RESUMO]. Objetivos. Examinar o impacto da pandemia de COVID-19 no acesso a tratamento de câncer no Chile, ana- lisando efeitos diferenciais por tipo de cobertura de assistência à saúde, gênero e idade. Métodos. Realizamos um estudo quase-experimental utilizando análise de séries temporais interrompidas. A partir de várias fontes de dados, efetuamos uma avaliação abrangente da utilização de atenção à saúde relacionada ao câncer, de janeiro de 2017 a dezembro de 2020. Ajustamos modelos binomiais negativos por grupos populacionais a vários tipos de serviços e diagnósticos. Resultados. Uma queda acentuada no uso da assistência médica oncológica em março foi seguida por uma recuperação lenta e incompleta ao longo de 2020. Cumulativamente, a utilização de serviços oncológicos, as confirmações de diagnóstico e os afastamentos do trabalho por doença foram reduzidos em um terço em 2020. Essa redução foi mais pronunciada em mulheres e usuários do sistema público de saúde. No total, 5132 pessoas com 4 cânceres comuns não foram diagnosticadas precocemente. Conclusões. A pandemia impôs pressão sobre o sistema de saúde chileno, reduzindo o acesso a serviços essenciais e causando um profundo impacto no tratamento do câncer. As reduções na prestação de serviços de oncologia precederam os lockdowns em larga escala e as interrupções na oferta de suprimentos. É impor- tante ressaltar que nem todos os grupos populacionais foram igualmente afetados e os padrões observados sugerem que as desigualdades de gênero e socioeconômicas foram exacerbadas.

An approach on the migratory processes in the north of Chile based on Y chromosome analysis.

OBJECTIVES: Northern Chile is an area characterized by a complex cultural and demographic trajectory. During the last few centuries, this complex trajectory has become the destination of intra- and intercontinental migratory waves. In this study, we analyzed the Y chromosome to evaluate how migratory and admixture patterns have affected the genetic composition of the populations in northern Chile compared with other populations of the country. METHODS: A total of 311 people from urban (Antofagasta and Calama), rural (Azapa and Camarones), and Native (Aymara and Atacameño) populations from northern Chile were characterized by 26 SNPs and the STR DYS393 of the Y chromosome, along with 69 individuals from Native populations (Mapuche, Pehuenche, and Huilliche) from southern Chile. In addition to characterizing the paternal lineages, multivariate analyses were performed to compare with published data from other Chilean populations. RESULTS: Both the Antofagasta and Calama populations show differences compared with the rest of the Chilean population. On one side, Antofagasta shows a high diversity of non-Amerindian lineages, including the highest value for haplogroup I (12%) for all Chileans populations. Otherwise, Calama has the highest value of any Chilean urban population (31.9%) for Amerindian lineages, including the only Q-M3 sub-lineage detected in the entire sample. Regarding the Native population, Aymara presents the highest percentage of Q-M3 (94.4%). CONCLUSIONS: The Y chromosome haplogroup distribution allowed us to identify recent migratory processes typical of the northern populations studied. These have shaped the demographic and cultural dynamics of local and migrant groups in the territory.

Exploring physical activity in Central Chile during the Early Ceramic Period and Late Intermediate Period (200-1450 CE).

OBJECTIVES: We explore physical activity in early farming societies of Central Chile during the Early Ceramic and Late Intermediate Periods (200-1450 CE), a time of technological changes and intensification of food production. The existence of differences in entheseal changes (EC) between females and males is evaluated in two periods with different subsistence strategies. MATERIAL AND METHODS: EC were recorded with method in the upper and lower limbs of 56 male and female adult individuals from the Early Ceramic Period (ECP) and Late Intermediate Period (LIP). Hierarchical multiple factor analysis and hierarchical clustering on principal components were performed using an exploratory approach. RESULTS: In all the analyzed limbs, the EC scores are higher in males than females, which may be explained by sexual dimorphism. A constant overlap in the variability of the EC among males and females is observed. However, the EC scores show a different pattern of variability when comparing ECP females with LIP females. The results show that the scores increase in the latter. In contrast, when comparing ECP males with LIP males scores decrease in the later period. DISCUSSION: Physical activity in the societies of Central Chile with incipient agriculture did not vary by sex or during the timeframe studied. Nevertheless, the interaction between sex-period and the variability pattern of the EC from one period to another suggests different ways of doing similar physical activities or different emphases for similar biomechanical actions.

Native American mitochondrial lineages in admixed populations from Chile: Detecting recent migrations during post-Columbian times using geographically restricted lineages.

OBJECTIVES: To analyze the mitochondrial diversity in three admixed populations and evaluate the historical migration effect of native southern population movement to Santiago (capital of Chile). The intensity of migration was quantified using three mitochondrial lineages restricted to South-Central native groups. METHODS: D-loop sequences were genotyped in 550 unrelated individuals from San Felipe-Los Andes (n = 108), Santiago (n = 217), and Concepción (n = 225). Sequence processing, alignment, and haplogroup inference were carried out, and different genetic structure analyses were performed for haplogroup frequencies and D-loop sequences. RESULTS: The Native lineages B2i2, C1b13, and D1g were the most frequent haplogroups, especially in Santiago (71.8%). Despite the distance, this city showed a high-genetic affinity with southern populations, including Concepción (~500 km distant) and native groups, rather than with those from San Felipe-Los Andes (<100 km distant). In fact, there was a negative correlation between geographical and genetic distance among these cities (r corr = -0.5593, p value = 0.8387). Network analysis revealed shared haplotypes between Santiago, Concepción, and other southern populations. Finally, we found lineages from Concepción acting as ancestral nodes in the northern clade. CONCLUSIONS: Considering the geographic distances from these cities, the results were not consistent with a model of genetic isolation by geographic distance, revealing the effects of a historical migration process from the south to the capital. We also show evidence of possible north-to-south migration during admixture onset in Concepción and in addition, we were able to identify previously unreported mitochondrial diversity in urban populations that became lost in Native groups post-European contact.

Ancestry and admixture of a southernmost Chilean population: The reflection of a migratory history.

OBJECTIVES: Punta Arenas is a Chilean city situated on ancestral Aönikenk territory. The city was founded by 19th- and 20th-century colonists from Chile (Chiloé) and Europe (Croatia). This work uses uniparental and ancestry-informative markers (AIMs) to explore the effects of historic migratory and admixture patterns on the current genetic composition of Punta Arenas. METHODS: We analyzed mitochondrial DNA (mtDNA), Y-chromosome single-nucleotide polymorphisms (SNPs), and 141 AIMs obtained from 129 DNA samples from male residents with regional ancestry. After characterizing uniparental lineages and ancestry proportions, multivariate analysis was used to explore relationships among the various types of data. RESULTS: Punta Arenas has an admixed population with three main genetic components: European (56.5%), northern Native (11.3%), and south-central Native (28.6%). The Native component is preponderant in the mtDNA (83.76%), while the foreign component predominates in the Y-chromosome (92.25%). Non-Native mtDNA lineages are associated with European genetic ancestry, and Native mtDNA lineages originated mainly in the southern and southernmost regions of Chile. Most non-Native Y-chromosome SNPs originated in Spain, and secondly, in Croatia. CONCLUSIONS: The population of Punta Arenas is mainly of Chilote origin with south-central Native and Spanish ancestral components, as well as some Croatian components. The persistence of local Native lineages is notable, suggesting continuity with the ancestral populations of the region such as the Kawésqar, Aönikenk, Yámana, or Selknam peoples. This study contributes to our knowledge of local history and its links to national and global developments in genetic ancestry.

Acceso a la atención del cáncer en los grupos vulnerables de Chile durante la pandemia de COVID-19 / Cancer care access in Chile's vulnerable populations during the COVID-19 pandemic / Acesso a tratamento de câncer em populações vulneráveis no Chile durante a pandemia de COVID-19

RESUMEN Objetivo. Estudiar la repercusión de la pandemia de COVID-19 en el acceso a la atención del cáncer en Chile, analizando los efectos diferenciales por tipo de seguro, sexo y edad. Métodos. Se llevó a cabo un estudio cuasiexperimental mediante análisis de series temporales interrumpidas. Se recurrió a fuentes de datos múltiples con el fin de lograr una evaluación amplia de la utilización de la atención del cáncer de enero del 2017 a diciembre del 2020. Se ajustaron modelos binomiales negativos en función de los grupos de población para una diversidad de servicios y diagnósticos. Resultados. Tras una disminución considerable de la utilización de la atención oncológica en marzo, se observó una recuperación lenta e incompleta durante el 2020. Los servicios de atención del cáncer, las confirmaciones diagnósticas y las licencias por enfermedad acumulados se redujeron en un tercio en el 2020; la disminución fue más pronunciada en las mujeres y las personas afiliadas al seguro de enfermedad público. No se hizo un diagnóstico temprano en 5132 personas con cuatro tipos frecuentes de cáncer. Conclusiones. La pandemia sobrecargó el sistema de salud chileno y provocó una disminución del acceso a los servicios básicos, con una repercusión profunda en la atención del cáncer. La reducción de los servicios de oncología precedió los confinamientos a gran escala y las interrupciones por parte de los prestadores. Cabe destacar que no todos los grupos de la población se vieron afectados por igual y se observaron pautas que indican un agravamiento de las desigualdades por situación socioeconómica y sexo.

ABSTRACT Objectives. To examine the COVID-19 pandemic's impact on cancer care access in Chile, analyzing differential effects by insurance type, gender, and age. Methods. We conducted a quasi-experimental study using interrupted time series analysis. We used multiple data sources for a broad evaluation of cancer-related health care utilization from January 2017 to December 2020. We fit negative binomial models by population groups for a range of services and diagnoses. Results. A sharp drop in oncology health care utilization in March was followed by a slow, incomplete recovery over 2020. Cumulative cancer-related services, diagnostic confirmations, and sick leaves were reduced by one third in 2020; the decrease was more pronounced among women and the publicly insured. Early diagnosis was missed in 5132 persons with 4 common cancers. Conclusions. The pandemic stressed the Chilean health system, decreasing access to essential services, with a profound impact on cancer care. Oncology service reductions preceded large-scale lockdowns and supply-side disruptions. Importantly, not all population groups were equally affected, with patterns suggesting that gender and socioeconomic inequalities were exacerbated.

RESUMO Objetivos. Examinar o impacto da pandemia de COVID-19 no acesso a tratamento de câncer no Chile, analisando efeitos diferenciais por tipo de cobertura de assistência à saúde, gênero e idade. Métodos. Realizamos um estudo quase-experimental utilizando análise de séries temporais interrompidas. A partir de várias fontes de dados, efetuamos uma avaliação abrangente da utilização de atenção à saúde relacionada ao câncer, de janeiro de 2017 a dezembro de 2020. Ajustamos modelos binomiais negativos por grupos populacionais a vários tipos de serviços e diagnósticos. Resultados. Uma queda acentuada no uso da assistência médica oncológica em março foi seguida por uma recuperação lenta e incompleta ao longo de 2020. Cumulativamente, a utilização de serviços oncológicos, as confirmações de diagnóstico e os afastamentos do trabalho por doença foram reduzidos em um terço em 2020. Essa redução foi mais pronunciada em mulheres e usuários do sistema público de saúde. No total, 5132 pessoas com 4 cânceres comuns não foram diagnosticadas precocemente. Conclusões. A pandemia impôs pressão sobre o sistema de saúde chileno, reduzindo o acesso a serviços essenciais e causando um profundo impacto no tratamento do câncer. As reduções na prestação de serviços de oncologia precederam os lockdowns em larga escala e as interrupções na oferta de suprimentos. É importante ressaltar que nem todos os grupos populacionais foram igualmente afetados e os padrões observados sugerem que as desigualdades de gênero e socioeconômicas foram exacerbadas.

[Design of a real and perceived academic workload measurement instrument for health care undergraduate students]. / Diseño y validación de un instrumento de medición de la carga académica de estudiantes de carreras de la salud.

BACKGROUND: A high academic workload may have adverse consequences among university students. AIM: To design and validate an instrument to measure both real and perceived academic workload for health care students. MATERIAL AND METHODS: The questionnaire was designed based on a bibliographic revision and the conduction of two focus groups conformed by undergraduate students from a Faculty of Medicine. Afterwards, it was submitted to qualitative pre-tests. The final instrument consists of a self-applied questionnaire with both a characterization section (10 questions) and one concerning academic workload by subject and semester (five and two questions, respectively). A national and international panel of 14 experts evaluated the survey content's validity. The analysis was performed according to the Content Validity Ratio and the Content Validity Index. RESULTS: The complete instrument was validated with an 84% consensus between the judges. Each section of the instrument was approved separately with a 77% and a 94% agreement, respectively. After being individually analyzed by the judges, each question was validated. The wording of questions was improved taking the experts comments into consideration. CONCLUSIONS: The proposed instrument constitutes a contribution for the measurement of real and perceived academic workload for students.

SARAF and EFHB Modulate Store-Operated Ca2+ Entry and Are Required for Cell Proliferation, Migration and Viability in Breast Cancer Cells.

Breast cancer is among the most common malignancies in women. From the molecular point of view, breast cancer can be grouped into different categories, including the luminal (estrogen receptor positive (ER+)) and triple negative subtypes, which show distinctive features and, thus, are sensitive to different therapies. Breast cancer cells are strongly dependent on Ca2+ influx. Store-operated Ca2+ entry (SOCE) has been found to support a variety of cancer hallmarks including cell viability, proliferation, migration, and metastasis. The Ca2+ channels of the Orai family and the endoplasmic reticulum Ca2+ sensor STIM1 are the essential components of SOCE, but the extent of Ca2+ influx is fine-tuned by several regulatory proteins, such as the STIM1 modulators SARAF and EFHB. Here, we show that the expression and/or function of SARAF and EFHB is altered in breast cancer cells and both proteins are required for cell proliferation, migration, and viability. EFHB expression is upregulated in luminal and triple negative breast cancer (TNBC) cells and is essential for full SOCE in these cells. SARAF expression was found to be similar in breast cancer and pre-neoplastic breast epithelial cells, and SARAF knockdown was found to result in enhanced SOCE in pre-neoplastic and TNBC cells. Interestingly, silencing SARAF expression in ER+ MCF7 cells led to attenuation of SOCE, thus suggesting a distinctive role for SARAF in this cell type. Finally, we used a combination of approaches to show that molecular knockdown of SARAF and EFHB significantly attenuates the ability of breast cancer cells to proliferate and migrate, as well as cell viability. In aggregate, SARAF and EFHB are required for the fine modulation of SOCE in breast cancer cells and play an important role in the maintenance of proliferation, migration, and viability in these cells.

Diseño y validación de un instrumento de medición de la carga académica de estudiantes de carreras de la salud / Design of a real and perceived academic workload measurement instrument for health care undergraduate students

Background: A high academic workload may have adverse consequences among university students. Aim: To design and validate an instrument to measure both real and perceived academic workload for health care students. Material and Methods: The questionnaire was designed based on a bibliographic revision and the conduction of two focus groups conformed by undergraduate students from a Faculty of Medicine. Afterwards, it was submitted to qualitative pre-tests. The final instrument consists of a self-applied questionnaire with both a characterization section (10 questions) and one concerning academic workload by subject and semester (five and two questions, respectively). A national and international panel of 14 experts evaluated the survey content's validity. The analysis was performed according to the Content Validity Ratio and the Content Validity Index. Results: The complete instrument was validated with an 84% consensus between the judges. Each section of the instrument was approved separately with a 77% and a 94% agreement, respectively. After being individually analyzed by the judges, each question was validated. The wording of questions was improved taking the experts comments into consideration. Conclusions: The proposed instrument constitutes a contribution for the measurement of real and perceived academic workload for students.

Melatonin downregulates TRPC6, impairing store-operated calcium entry in triple-negative breast cancer cells.

Melatonin has been reported to induce effective reduction in growth and development in a variety of tumors, including breast cancer. In triple-negative breast cancer (TNBC) cells, melatonin attenuates a variety of cancer features, such as tumor growth and apoptosis resistance, through a number of still poorly characterized mechanisms. One biological process that is important for TNBC cells is store-operated Ca2+ entry (SOCE), which is modulated by TRPC6 expression and function. We wondered whether melatonin might intersect with this pathway as part of its anticancer activity. We show that melatonin, in the nanomolar range, significantly attenuates TNBC MDA-MB-231 cell viability, proliferation, and migration in a time- and concentration-dependent manner, without having any effect on nontumoral breast epithelial MCF10A cells. Pretreatment with different concentrations of melatonin significantly reduced SOCE in MDA-MB-231 cells without altering Ca2+ release from the intracellular stores. By contrast, SOCE in MCF10A cells was unaffected by melatonin. In the TNBC MDA-MB-468 cell line, melatonin not only attenuated viability, migration, and SOCE, but also reduced TRPC6 expression in a time- and concentration-dependent manner, without altering expression or function of the Ca2+ channel Orai1. The expression of exogenous TRPC6 overcame the effect of melatonin on SOCE and cell proliferation, and silencing or inhibition of TRPC6 impaired the inhibitory effect of melatonin on SOCE. These findings indicate that TRPC6 downregulation might be involved in melatonin's inhibitory effects on Ca2+ influx and the maintenance of cancer hallmarks and point toward a novel antitumoral mechanism of melatonin in TNBC cells.

Comparison of nutritional screening tools to assess nutritional risk and predict clinical outcomes in Mexican patients with digestive diseases.

BACKGROUND: The prevalence of malnutrition remains high in hospitals but no "gold standard" has been established to identify nutritional risks adequately. The Nutrition Risk Screening-2002 (NRS-2002), Subjective Global Assessment (SGA), and Controlling Nutritional Status Index (CONUT) are widely used screening tools, but their efficacy has not yet been compared in Mexican patients. Here, we aimed to compare the efficacy of these tools in identifying nutritional risks within the first 48 h of admission in a group of patients with gastrointestinal diseases. METHODS: This was a cross-sectional study of 196 patients. The results of the screening tools, length of hospital stay, serum albumin and cholesterol concentrations, lymphocyte counts, age, body mass index (BMI), complications, and mortality were analyzed. Kappa (κ) statistics were applied to determine the degree of agreement between tools. The performances of the screening tools in predicting complications and mortality were assessed using binary logistic regression. RESULTS: The NRS-2002, SGA, and CONUT tools identified nutritional risk in 67, 74, and 51% of the patients, respectively. The observed agreements between tools were: NRS2002/SGA, κ = 0.53; CONUT/NRS-2002, κ = 0.42; and SGA/CONUT, κ = 0.36. Within age groups, the best agreement was found in those aged 51-65 years (κ = 0.68). CONUT and length of stay were both predictive for the number of complications. The number of complications and serum cholesterol concentrations were predictive for mortality. CONCLUSIONS: The proportion of patients identified as having nutritional risk was high using all three screening tools. SGA, NRS-2002, and CONUT had similar capacities for screening risk, but the best agreement was observed between NRS-2002 and SGA. Only CONUT predicted complications, but none of these tools performed well in predicting mortality.

Clinical evaluation of the antifungal effect of sertraline in the treatment of cryptococcal meningitis in HIV patients: a single Mexican center experience.

PURPOSE: Cryptococcal meningitis is a potentially fatal fungal infection associated with a significant attributable morbidity and mortality, especially among HIV/AIDS patients. The first-line therapy for the treatment of this clinical entity is the combinatory therapy of amphotericin B plus flucytosine. However, the high cost, toxic effects, and limited repertoire of effective antifungal drugs have led to the investigation of novel molecules. This is a prospective, double-blinded, and randomized study performed in a Mexican tertiary care center to evaluate the antifungal activity of sertraline in the treatment of cryptococcal meningitis in HIV patients. METHODS: During June 2015-December 2016, patients were recruited and included in one of two study groups: group A was given standard antifungal treatment plus sertraline 200 mg/day, while group B was given standard antifungal plus placebo. Lumbar punctures were performed on days 0, 7, and 14 of the study, and cryptococcal antigenemia and quantitative fungal culture in cerebrospinal fluid at each time point were evaluated to measure the rate of fungal clearance. RESULTS: The fungal loads and cryptococcal antigenemia titers showed a marked tendency to decrease by day 14 in both groups. Otherwise, group B exhibited a slightly higher nonstatistical rate of fungal clearance (-0.2868 ± 0.08275 log CFU/ml/day) than group A (-0.2496 ± 0.08340 log CFU/ml/day). CONCLUSIONS: A statistical difference between study groups was not found. This is the first study in Latin America that reports the experience of using sertraline as an adjuvant in the antifungal management of cryptococcal meningitis in HIV patients.

Solvation Thermodynamic Properties of Hydrogen Sulfide in [C4mim][PF6], [C4mim][BF4], and [C4mim][Cl] Ionic Liquids, Determined by Molecular Simulations.

Removal of hydrogen sulfide (H2S) and acid gases from natural gas is accomplished by absorption processes using a solvent. The gas solubility in a liquid can be used to measure the degree of removal of the gas and is quantified by the Henry's constant, the free energy of solvation at infinite dilution, or the excess chemical potential. In this work, Henry's constants and thermodynamic properties of solvation of H2S were calculated in three ionic liquids: [C4mim][PF6], [C4mim][BF4], and [C4mim][Cl] ([C4mim], 1-butyl-3-methyl imidazolium). The first step in this work was the evaluation of the force fields for the gas and condensed phases in order to obtain accurate values for the excess chemical potential for H2S on each ionic liquid using free energy perturbation techniques. In the H2S-[C4mim][PF6] and H2S-[C4mim][BF4] systems, the results obtained by molecular simulation agree with the experimental values reported in the literature. However, the solvation free energy calculated for the H2S-[C4mim][Cl] system can be considered predictive because of the lack of experimental data at the simulated conditions. Based on these results, the best solvent for removing H2S is [C4mim][Cl] because it has the highest affinity for this species (lowest value of the Henry's constant). Also, solvation thermodynamic properties such as enthalpy and entropy were calculated in order to evaluate their contribution to the free energy of solvation.