Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma.

Glioblastoma multiforme (GBM) exhibits genetic alterations that induce the deregulation of oncogenic pathways, thus promoting metabolic adaptation. The modulation of metabolic enzyme activities is necessary to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates essential for fulfilling the biosynthetic needs of glioma cells. Moreover, the TCA cycle produces intermediates that play important roles in the metabolism of glucose, fatty acids, or non-essential amino acids, and act as signaling molecules associated with the activation of oncogenic pathways, transcriptional changes, and epigenetic modifications. In this review, we aim to explore how dysregulated metabolic enzymes from the TCA cycle and oxidative phosphorylation, along with their metabolites, modulate both catabolic and anabolic metabolic pathways, as well as pro-oncogenic signaling pathways, transcriptional changes, and epigenetic modifications in GBM cells, contributing to the formation, survival, growth, and invasion of glioma cells. Additionally, we discuss promising therapeutic strategies targeting key players in metabolic regulation. Therefore, understanding metabolic reprogramming is necessary to fully comprehend the biology of malignant gliomas and significantly improve patient survival.

Social gradient and rural-urban disparities in cancer mortality in Costa Rica.

INTRODUCTION: Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer mortality in Costa Rica between 2010 and 2018. METHODS: We linked 9-years of data from the National Electoral Rolls, National Birth Index and National Death Index to classify deaths due to cancer and socioeconomic characteristics of the district of residence, as measured by levels of urbanicity and wealth. We analyzed the fifteen most frequent cancer sites in Costa Rica among the 2.7 million inhabitants aged 20 years and older. We used a parametric survival model based on a Gompertz distribution. RESULTS: Compared to urban areas, mixed and rural area residents had lower mortality from pancreas, lung, breast, prostate, kidney, and bladder cancers, and higher mortality from stomach cancer. Mortality from stomach, lung and cervical cancer was higher, and mortality from colorectal cancer, non-Hodgkin lymphoma and leukemia was lower in the most disadvantaged districts, compared to the wealthiest ones. CONCLUSION: We observed marked disparities in cancer mortality in Costa Rica in particular from infection- and lifestyle- related cancers. There are important opportunities to reduce disparities in cancer mortality by targeting cancer prevention, early detection and opportune treatment, mainly in urban and disadvantaged districts.

COVID-19 and long-term impact on symptoms and Health-Related Quality of Life in Costa Rica: the RESPIRA cohort study.

BACKGROUND: Evidence continues to accumulate regarding the potential long-term health consequences of COVID-19 in the population. To distinguish between COVID-19-related symptoms and health limitations from those caused by other conditions, it is essential to compare cases with community controls using prospective data ensuring case-control status. The RESPIRA study addresses this need by investigating the lasting impact of COVID-19 on Health-related Quality of Life (HRQoL) and symptomatology in a population-based cohort in Costa Rica, thereby providing a robust framework for controlling HRQoL and symptoms. METHODS: The study comprised 641 PCR-confirmed, unvaccinated cases of COVID-19 and 947 matched population-based controls. Infection was confirmed using antibody tests on enrollment serum samples and symptoms were monitored monthly for 6 months post-enrolment. Administered at the 6-month visit (occurring between 6- and 2-months post-diagnosis for cases and 6 months after enrollment for controls), HRQoL and Self-Perceived Health Change were assessed using the SF-36, while brain fog, using three items from the Mental Health Inventory (MHI). Regression models were utilized to analyze SF-36, MHI scores, and Self-Perceived Health Change, adjusted for case/control status, severity (mild case, moderate case, hospitalized) and additional independent variables. Sensitivity analyses confirmed the robustness of the findings. RESULTS: Cases showed significantly higher prevalences of joint pain, chest tightness, and skin manifestations, that stabilized at higher frequencies from the fourth month post-diagnosis onwards (2.0%, 1.2%, and 0.8% respectively) compared to controls (0.9%, 0.4%, 0.2% respectively). Cases also exhibited significantly lower HRQoL than controls across all dimensions in the fully adjusted model, with a 12.4 percentage-point difference [95%CI: 9.4-14.6], in self-reported health compared to one year prior. Cases reported 8.0% [95%CI: 4.2, 11.5] more physical limitations, 7.3% [95%CI: 3.5, 10.5] increased lack of vitality, and 6.0% [95%CI: 2.4, 9.0] more brain fog compared to controls with similar characteristics. Undiagnosed cases detected with antibody tests among controls had HRQoL comparable to antibody negative controls. Differences were more pronounced in individuals with moderate or severe disease and among women. CONCLUSIONS: PCR-confirmed unvaccinated cases experienced prolonged HRQoL reductions 6 months to 2 years after diagnosis, this was particularly the case in severe cases and among women. Mildly symptomatic cases showed no significant long-term sequelae.

Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations in the hypoxic tumor microenvironment, as well as in transcriptional and signaling networks, which result in changes in global genetic expression. The signaling pathways PI3K/AKT/mTOR and RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, by modulating the transcriptional factors p53, HIF1, and c-Myc. The overexpression of HIF1 and c-Myc, master regulators of cellular metabolism, is a key contributor to the synthesis of bioenergetic molecules that mediate glioma cell transformation, proliferation, survival, migration, and invasion by modifying the transcription levels of key gene groups involved in metabolism. Meanwhile, the tumor-suppressing protein p53, which negatively regulates HIF1 and c-Myc, is often lost in glioblastoma. Alterations in this triad of transcriptional factors induce a metabolic shift in glioma cells that allows them to adapt and survive changes such as mutations, hypoxia, acidosis, the presence of reactive oxygen species, and nutrient deprivation, by modulating the activity and expression of signaling molecules, enzymes, metabolites, transporters, and regulators involved in glycolysis and glutamine metabolism, the pentose phosphate cycle, the tricarboxylic acid cycle, and oxidative phosphorylation, as well as the synthesis and degradation of fatty acids and nucleic acids. This review summarizes our current knowledge on the role of HIF1, c-Myc, and p53 in the genic regulatory network for metabolism in glioma cells, as well as potential therapeutic inhibitors of these factors.

Knowledge, attitudes and practices related to oral health in First-Year university students of the Paraíso campus of the University of Costa Rica / Conocimientos, actitudes y prácticas relacionadas con la salud bucal en estudiantes universitarios de primer año del Recinto de Paraíso de la Universidad de Costa Rica

Abstract People's knowledge, attitudes, and practices related to health are built throughout life, particularly during childhood and adolescence, and they reflect the practices of their family and social circle. The aim of this study was to identify the levels of knowledge, attitudes, and practices related to oral health of first-year university students at the Paraíso Campus of the University of Costa Rica. This was done through a questionnaire of closed questions that would allow oral health educational strategies to be established in the future for this population group. For this purpose, a cross-sectional descriptive study was conducted, where 70 first-year students of the Paraíso Campus participated in the first semester of the year 2019. For data collection, a survey of 22 closed questions on knowledge, attitudes, and practices about oral health was applied, and a score on oral health knowledge was subsequently performed, based on the answers to the questions. According to the results, the level of knowledge shown about oral health is low, since the average knowledge score (7.02 points) was less than half of the maximum score (17 points). The greatest deficiency in knowledge was evidenced in topics, such as, dental biofilm, gingivitis, use of fluorides, and the role of saliva. In addition, several practices that affect the condition of the oral cavity were identified, such as harmful habits, inadequate nutrition, and poor oral hygiene habits. In this study, a general lack of knowledge was identified regarding basic concepts of oral health in young university students, who are not clear about the role of some protective or risk factors related to the main oral diseases.

Resumen Los conocimientos, actitudes y prácticas relacionados a la salud en las personas se construyen a través de la vida, particularmente durante la infancia y la adolescencia y reflejan las prácticas de su círculo familiar y social. El objetivo de este estudio fue identificar los niveles de conocimiento, las actitudes y las prácticas relacionadas a la salud bucodental en estudiantes universitarios de primer ingreso en el Recinto de Paraíso de la Universidad de Costa Rica, mediante un cuestionario de preguntas cerradas que permitirá a futuro establecer estrategias educativas en salud bucal para este grupo de población. Se trató de un estudio descriptivo transversal de tipo observacional en 70 estudiantes de primer ingreso del Recinto de Paraíso en el I semestre del año 2019. Para la recolección de datos se aplicó una encuesta de 22 preguntas cerradas sobre los conocimientos, las actitudes y las prácticas sobre la salud oral. A partir de las preguntas sobre conocimiento en salud bucal se creó un puntaje de conocimiento. Se pudo evidenciar que el nivel de conocimiento sobre la salud bucal es bajo, ya que el promedio del puntaje de conocimiento (7,02 puntos) es menos de la mitad del puntaje máximo (17 puntos). La mayor deficiencia en el conocimiento se evidenció en temas como el biofilm dental, gingivitis, uso de fluoruros y el rol de la saliva. Además, se identificaron varias prácticas que afectan la condición de la cavidad bucal, como los hábitos nocivos, una alimentación inadecuada y hábitos de higiene oral deficiente. En este estudio se identificó en general una falta de conocimiento respecto a conceptos básicos de salud bucal en personas jóvenes universitarias, quienes no tienen claro la función de algunos factores protectores o de riesgo relacionados con las principales enfermedades bucales.

Health inequalities in the geographic distribution of dental practitioners in Costa Rica: An ecological study.

OBJECTIVE: The uneven distribution of dental health services in a territory can cause an imbalance in accessibility, increasing health inequalities. This study aimed to describe the geographical distribution of dental health practitioners according to urbanicity and area-level socio-economic status in Costa Rica. METHODS: A National Dentist Survey was developed to identify employment status, number of working hours, address and list of the working clinics. Data was completed using information from the national College of Surgeons, including all Costa Rican dentists. The Minimal Geographic Units (MGU) allowed for aggregating the population's individual level socio-economic position. Local Potential Accessibility (LPA) calculated the density of full-time hour's equivalents around each MGU using floating sectors. Clinics were geocoded using Geographic Information Systems, creating 2853 clinical points. Distance between each MGU and the nearest accessible clinics considering full-time working hours equivalents was estimated. MGU were divided into six categories: 'No accessibility', 'Very low accessibility', 'Low accessibility', 'Good accessibility' 'High accessibility' and 'Very high accessibility'. RESULTS: Mean national LPA was 6.5 full-time equivalents per 10 000 inhabitants, 3.4% of the Costa Rican population had no access to dentist; 12.9% had very low accessibility, 22.7% had low accessibility, 35.0% had good accessibility, 16.2% had high accessibility, and 9.8% had very high accessibility. Overall, 39% of the population has a rather low accessibility. LPA was higher in urban districts compared to rural districts and in wealthiest districts compared to most disadvantaged districts. Within districts, after adjustment for district's characteristics, LPA was higher in urban MGU compared to rural MGU and in wealthiest MGU compared to most disadvantaged MGU. CONCLUSIONS: This study found that despite having a high number of dentists, their numbers are small in many areas, increasing inequalities in access to health care. The dentist's free establishment, where they can decide to provide private services within a community, creates zones with very high densities, in particular in the wealthiest urban areas, and others with very low densities, in particular the poorest rural areas. The lack of territorial planning has been one of the reasons that has encouraged an imbalance in the availability of dental human resources. To achieve effective universal health coverage, public institutions should focus their efforts on improving access to dental services in underserved areas.

Cohort profile: evaluation of immune response and household transmission of SARS-CoV-2 in Costa Rica: the RESPIRA study.

PURPOSE: The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19. PARTICIPANTS: From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence. FINDINGS TO DATE: Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up. FUTURE PLANS: RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024. TRIAL REGISTRATION NUMBER: NCT04537338.

Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.

Glioma cells exhibit genetic and metabolic alterations that affect the deregulation of several cellular signal transduction pathways, including those related to glucose metabolism. Moreover, oncogenic signaling pathways induce the expression of metabolic genes, increasing the metabolic enzyme activities and thus the critical biosynthetic pathways to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates that are essential to accomplish the biosynthetic needs of glioma cells. In this review, we aim to explore how dysregulated metabolic enzymes and their metabolites from primary metabolism pathways in glioblastoma (GBM) such as glycolysis and glutaminolysis modulate anabolic and catabolic metabolic pathways as well as pro-oncogenic signaling and contribute to the formation, survival, growth, and malignancy of glioma cells. Also, we discuss promising therapeutic strategies by targeting the key players in metabolic regulation. Therefore, the knowledge of metabolic reprogramming is necessary to fully understand the biology of malignant gliomas to improve patient survival significantly.

Transsulfuration pathway: a targeting neuromodulator in Parkinson's disease.

The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, H2S, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine ß-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease.

Prevalence of tooth loss, bleeding on probing and malocclusion as oral disease indicators in Costa Rican male adolescents: a cross sectional study / Prevalencia de la pérdida de piezas dentales, del sangrado al sondeo y la maloclusión como indicadores de enfermedades orales en adolescentes varones costarricenses: un estudio transversal

The evidence to characterize oral health during adolescence in Costa Rica is limited. This lack of adequate research makes it difficult to develop appropriate health policies for this subgroup of the population. This is particularly important because adolescence is the period during which good health habits must take root in order to foster good physical and cognitive development. This study aims to determine the prevalence of tooth loss, bleeding on probing and malocclusion in Costa Rican male adolescents at the ''Colegio Técnico Profesional San Agustín'' (St. Augustine's Technical High School) located in the province of Cartago. Data was collected from 428 male adolescents aged 12-22 years in a cross-sectional study during 2019. Prevalence of tooth loss was calculated as the number of individuals having lost at least one tooth. The average number of teeth lost by individuals was also recorded. The bleeding on probing was an indicator used as a proxy parameter for monitoring periodontal health where the presence of bleeding on probing and calculus was also recorded. Malocclusion was measured using the Dental Aesthetic Index (DAI). The results showed that the prevalence of tooth loss, bleeding on probing and malocclusion was of 19%, 70.0% and 98%, respectively. It was also found that 81% of the participants had all their teeth, 11% had lost 1 tooth, 8% had lost more than one tooth of which 0.5% had lost more than 5 teeth. Considering a general classification of periodontal problems based on bleeding on probing and presence of calculus, the prevalence of periodontal problems increases to 92%. Regarding the DAI, the category identifying a very severe malocclusion was the most prevalent in the sample (88%). It is alarming the high prevalence of tooth loss, bleeding on probing, and malocclusions in a sample of Costa Rican male adolescents, compared to similar studies in other countries. The overarching conclusion of this study is that oral diseases represent an important health problem that urgently need proper public health action.

La evidencia para caracterizar la salud bucal durante la adolescencia en Costa Rica es limitada. Esta falta de investigación adecuada dificulta el desarrollo de políticas de salud convenientes para este subgrupo de la población. Esto es particularmente importante porque la adolescencia es el período durante el cual se deben arraigar buenos hábitos de salud para fomentar un buen desarrollo físico y cognitivo. Este estudio tiene como objetivo determinar la prevalencia de pérdida de piezas dentales, sangrado al sondeo y maloclusión en adolescentes varones costarricenses del Colegio Técnico Profesional San Agustín ubicado en la provincia de Cartago. Se recopilaron datos de 428 adolescentes varones de 12 a 22 años en un estudio transversal durante 2019. La prevalencia de pérdida de piezas dentales se calculó como el número de individuos que habían perdido al menos una pieza dental. También se registró el número promedio de dientes perdidos por individuos. El sangrado al sondeo fue un indicador utilizado como parámetro para el seguimiento de la salud periodontal donde también se registró la presencia de sangrado al sondeo y cálculo dental. La maloclusión se midió utilizando el Índice Estético Dental (DAI, por sus siglas en inglés). Los resultados mostraron que la prevalencia de pérdida de piezas dentales, sangrado al sondeo y maloclusión fue del 19%, 70,0% y 98%, respectivamente. También se encontró que el 81% de los participantes tenían todos sus dientes, el 11% había perdido 1 pieza dental, el 8% había perdido más de una pieza dental, de los cuales el 0,5% había perdido más de 5 piezas dentales. Considerando una clasificación general de problemas periodontales basada en sangrado al sondeo y presencia de cálculo, la prevalencia de problemas periodontales aumenta al 92%. En cuanto al DAI, la categoría que identifica una maloclusión muy severa fue la más prevalente en la muestra (88%). Es alarmante la alta prevalencia de pérdida de piezas dentales, sangrado al sondeo y maloclusiones en una muestra de adolescentes varones costarricenses, en comparación con estudios similares en otros países. La conclusión general de este estudio es que las enfermedades bucodentales representan un importante problema de salud que necesita urgentemente una acción adecuada de salud pública.

Excess mortality from COVID 19 in Costa Rica: a registry based study using Poisson regression.

Background: Official death toll related to COVID-19 has been considerably underestimated in reports from some Latin American countries. This study aimed to analyze the mortality associated with the COVID-19 pandemic in Costa Rica between March 2020 and December 2021. Methods: A registry based study based on 2017-2021 data from the National Institute of Statistics and Census was designed (N = 128,106). Excess deaths were defined by the WHO as "the difference in the total number of deaths in a crisis compared to those expected under normal conditions"; and were estimated using a Poisson regression, and mortality and years of potential life lost (YPLL) rates were calculated. Findings: The COVID-19 pandemic represented 15% of the deaths in Costa Rica between March 2020 and December 2021. The mortality rate related to COVID-19 was 83 per 100,000 person-years. Between March and July 2020 (low-incidence period), observed number of deaths was 9%-lower than expected, whereas it was 15% and 24% higher than expected between July 2020 and March 2021 (high incidence period - no vaccination), and between March 2021 and December 2021 (high incidence period - progressive vaccination) respectively. Between July 2020 and December 2021, excess deaths observed and COVID-19 deaths reported were comparable (7461 and 7620 respectively). Nevertheless, there were more deaths than expected for conditions that predispose to COVID-19 deaths. YPLL and mortality rates increased with age, but significant excess deaths were observed in all age-groups older than 30-39 years. No large differences were noted by districts' socioeconomic characteristics although excess death rate was lower in rural compared to urban areas. Interpretation: Reporting of deaths was only slightly underestimated. In the pre-vaccination period, mortality rate and YPLL rates increased with age, being highest in people aged 60 years or older and justifying the decision to initially prioritize vaccination of older individuals. Funding: The study was supported by the University of Costa Rica and the Agencia Costarricense de Investigaciones Biomédicas - Fundación Inciensa.

Health inequalities in cause-specific mortality in Costa Rica: a population-based cohort study.

OBJECTIVE: To analyze health inequalities in cause-specific mortality in Costa Rica from 2010 to 2018, observing the main causes for inequality in the country. METHODS: The National Electoral Rolls were used to follow-up all Costa Rican adults aged 20 years or older from 2010 to 2018 (n = 2,739,733) in an ecological study. A parametric survival model based on the Gompertz distribution was performed and the event death was classified according to the ICD-10. RESULTS: After adjustment for urbanicity, the poorest districts had a higher mortality than the wealthier districts for most causes of death except neoplasms, mental and behavioral disorders, and diseases of the nervous system. Urban districts showed significantly higher mortality than mixed and rural districts after adjustment for wealth for most causes except mental and behavioral disorders, diseases of the nervous system, and diseases of the respiratory system. Differences according to wealth were more frequent in women than men, whereas differences according to urbanicity were more frequent in men than in women. CONCLUSIONS: The study's findings were consistent, but not fully similar, to the international literature.

Health inequalities in cause-specific mortality in Costa Rica: a population-based cohort study

ABSTRACT OBJECTIVE To analyze health inequalities in cause-specific mortality in Costa Rica from 2010 to 2018, observing the main causes for inequality in the country. METHODS The National Electoral Rolls were used to follow-up all Costa Rican adults aged 20 years or older from 2010 to 2018 (n = 2,739,733) in an ecological study. A parametric survival model based on the Gompertz distribution was performed and the event death was classified according to the ICD-10. RESULTS After adjustment for urbanicity, the poorest districts had a higher mortality than the wealthier districts for most causes of death except neoplasms, mental and behavioral disorders, and diseases of the nervous system. Urban districts showed significantly higher mortality than mixed and rural districts after adjustment for wealth for most causes except mental and behavioral disorders, diseases of the nervous system, and diseases of the respiratory system. Differences according to wealth were more frequent in women than men, whereas differences according to urbanicity were more frequent in men than in women. CONCLUSIONS The study's findings were consistent, but not fully similar, to the international literature.

Diferencias de mortalidad y sus causas: un estudio comparativo entre las zonas indígenas y no indígenas de Costa Rica

Introducción: En la mayoría de los países de los continentes americanos y oceánicos, las personas indígenas tienen peores indicadores de salud que el resto de la población. El objetivo de este estudio es analizar las diferencias de mortalidad y de causas de muerte entre las zonas indígenas y el resto de Costa Rica, en el periodo de 2010 a 2018. Metodología: La población de estudio se conformó a partir del padrón electoral de las elecciones presidenciales de 2010 y las causas de muerte (ICD-10) se extrajeron del registro del Instituto Nacional de Estadísticas y Censos (INEC); fueron incluidas 2 747 616 personas para 23 985 602 personas-año de seguimiento. Resultados: No se observaron diferencias de mortalidad entre los hombres de ambas poblaciones. En cambio, la mortalidad fue ligeramente superior en las mujeres indígenas. En las zonas indígenas, por un lado, la mortalidad fue más alta en quienes tenían menos de 50 años al inicio del seguimiento, en particular, por enfermedades del sistema digestivo y causas externas de morbilidad y mortalidad; por otro, fue inferior en mayores de 70 años y se debió a tumores y enfermedades del sistema circulatorio. Conclusiones: Los resultados obtenidos no confirman la hipótesis de una mortalidad sistemáticamente mayor en las poblaciones que viven en las zonas indígenas.

Introduction: In most countries of the American and Oceanic continents, indigenous people have worse health indicators than the rest of the population. The objective of this study is to analyze the differences in mortality and causes of death between people living in indigenous areas, and people living in the rest of Costa Rica, between 2010 and 2018. Methods: . The study population is based on the 2010 National Electoral Rolls. The Registry of the National Institute of Statistics and Censuses (INEC) allowed knowing the cause of death (ICD-10). 2,747,616 people for 23,985,602 person-years of follow-up were included. Results: No differences in mortality in men were observed between both populations. In women, mortality was slightly higher in indigenous areas. In indigenous areas, mortality was higher in people who were under 50 years of age at the beginning of the follow-up, compared to the rest of the population, in particular mortality due to Diseases of the digestive system and External causes of morbidity and mortality. Mortality was lower in indigenous areas in people over 70 years of age, particularly mortality due to Tumors and Diseases of the circulatory system. Conclusion: The results of this study do not confirm the hypothesis of systematically higher mortality in populations living in indigenous areas.

Estimating vaccine effectiveness against SARS-CoV-2 infection, hospitalization and death from ecologic data in Costa Rica.

BACKGROUND: Clinical trials and individual-level observational data in Israel demonstrated approximately 95% effectiveness of mRNA-based vaccines against symptomatic SARS-CoV-2 infection. Individual-level data are not available in many countries, particularly low- and middle- income countries. Using a novel Poisson regression model, we analyzed ecologic data in Costa Rica to estimate vaccine effectiveness and assess the usefulness of this approach. METHODS: We used national data from December 1, 2020 to May 13, 2021 to ascertain incidence, hospitalizations and deaths within ecologic units defined by 14 age groups, gender, 105 geographic areas, and day of the epidemic. Within each unit we used the proportions of the population with one and with two vaccinations, primarily tozinameran. Using a non-standard Poisson regression model that included an ecologic-unit-specific rate factor to describe rates without vaccination and a factor that depended on vaccine effectiveness parameters and proportions vaccinated, we estimated vaccine effectiveness. RESULTS: In 3.621 million persons aged 20 or older, there were 125,031 incident cases, 7716 hospitalizations, and 1929 deaths following SARS-CoV-2 diagnosis; 73% of those aged ≥ 75 years received two doses. For one dose, estimated effectiveness was 59% (95% confidence interval 53% to 64%) for SARS-CoV-2 incidence, 76% (68% to 85%) for hospitalizations, and 63% (47% to 80%) for deaths. For two doses, the respective estimates of effectiveness were 93% (90% to 96%), 100% (97% to 100%), and 100% (97% to 100%). CONCLUSIONS: These effectiveness estimates agree well with findings from clinical trials and individual-level observational studies and indicate high effectiveness in the general population of Costa Rica. This novel statistical approach is promising for countries where ecologic, but not individual-level, data are available. The method could also be adapted to monitor vaccine effectiveness over calendar time.

Identificación de las zonas con dificultades geográficas de acceso a los servicios públicos de salud en Costa Rica: una propuesta metodológica / Identification of areas with geographical access difficulties to public health services in Costa Rica: a methodological proposal

Objetivo: el propósito de este estudio es presentar y aplicar una herramienta metodológica para identificar las zonas en las cuales el acceso a los servicios de salud pudiera resultar difícil para la población debido a la barrera geográfica, tanto por su distancia al centro médico, como por su capacidad de desplazamiento, específicamente en los cantones de Curridabat, Escazú y Desamparados. Métodos: a partir de la división geográfica del país en unidades geoestadísticas mínimas realizada por el Instituto Nacional de Estadísticas y Censos, se calculó, por cada unidad, la distancia en minutos que se tardaría en recorrer caminando, por la ruta real más rápida, desde la unidad geoestadística mínima hasta la sede de su equipo básico de atención en salud asignado. Resultados: el 3,4% de la población estudiada vivía en una unidad geoestadística mínima clasificada como con dificultad importante de acceso a los servicios de salud, pues presentaba tanto la barrera física de la distancia, como poco desplazamiento en automotores y baja condición socioeconómica. Se identificaron 65 unidades geoestadísticas mínimas (sobre 2014 incluidas en el estudio) que se encontraban a más de 20 minutos caminando de la sede de su equipo básico de atención en salud y cuya población contaba con baja capacidad de desplazamiento y baja condición socioeconómica; la mayoría de ellas en el Área de Salud de Desamparados. Conclusión: este estudio presenta una herramienta metodológica para aplicar en la identificación de zonas a cuya población le pudiera resultar difícil el acceso geográfico a los servicios de salud, tanto por su distancia a un centro médico, como por su capacidad de desplazamiento, específicamente en los cantones de Curridabat, Escazú y Desamparados.

Aim: The objective of this study is to present and apply a methodological tool to identify the areas in which the inhabitants could have geographic access difficulties as a barrier to access to health services, both because of its distance from the health center and its mobility capacity, specifically in the cantons of Curridabat, Escazú and Desamparados. Methods: Based on the geographical division of the country into minimum geostatistical units carried out by the Instituto Nacional de Estadísticas y Censos, the distance in minutes that it would take to walk it was calculated for each unit, based on the actual fastest route between the minimum geostatistical unit and the headquarters of its assigned basic health care team. Results: An 3.4% of the studied population lived in a minimum geostatistical unit classified as having significant difficulty accessing health services since they accumulated both the physical barrier of distance and little mobility in automobiles. 65 minimum geostatistical units were identified (out of 2014 included in the study) as being at more than 20 minutes walking from the basic health care team, with a population with low mobility capacity, and consequently low socioeconomic status. Most of these were found in the Desamparados Health Area. Conclusion: This study presents and applies a methodological tool to identify the areas in which the inhabitants could have geographic access difficulties as a barrier to access to health services, both due to their distance from the health center and their mobility capacity, in Curridabat, Escazú and Desamparados.

Hypoxia as a Modulator of Inflammation and Immune Response in Cancer.

A clear association between hypoxia and cancer has heretofore been established; however, it has not been completely developed. In this sense, the understanding of the tumoral microenvironment is critical to dissect the complexity of cancer, including the reduction in oxygen distribution inside the tumoral mass, defined as tumoral hypoxia. Moreover, hypoxia not only influences the tumoral cells but also the surrounding cells, including those related to the inflammatory processes. In this review, we analyze the participation of HIF, NF-κB, and STAT signaling pathways as the main components that interconnect hypoxia and immune response and how they modulate tumoral growth. In addition, we closely examine the participation of the immune cells and how they are affected by hypoxia, the effects of the progression of cancer, and some innovative applications that take advantage of this knowledge, to suggest potential therapies. Therefore, we contribute to the understanding of the complexity of cancer to propose innovative therapeutic strategies in the future.

Social inequality in incidence and mortality of malignant neoplasms of lip, oral cavity and pharynx: Is Costa Rica an international paradox?

OBJECTIVES: Low socioeconomic position (SEP) has been associated with higher incidences and mortality of lip, oral cavity and pharynx (LOP) cancers in the vast majority of countries with available data. The origins of health inequalities in cancer are socioeconomic, although they vary by time and country. Evidence from Low-and Middle-income Countries (LMICs) remains scarce. This study aims to identify and describe socioeconomic inequalities in LOP cancers incidence and mortality in Costa Rica. The hypothesis tested is that people leaving in low-SEP districts in Costa Rica have greater incidence and mortality rates of lip, oral cavity and pharynx cancers. METHODS: The 10th revision of the International Classification of Diseases (ICD-10) was used to define cancer sites. Data come from a national population-based Cancer Registry with 100% completeness to study incidence. Incidence rate included all new cases of LOP cancer diagnosed from January 1, 2011, and December 31, 2015, for a total of 2 798 517 individuals, 13 832 524 years of follow-up and 601 LOP cases. Mortality rate was extracted from the National Death Index, including 2 739 733 individuals, 23 950 240 person-years of follow-up and 586 LOP cancer deaths, from January 1, 2010, to December 31, 2018. The 2011 Census (with 94% of Costa Rican inhabitants) was used to characterize the urbanicity and wealth of 477 districts. Survival models were performed for both incidence and mortality, allowing to consider existing competitive risks. Cox models were used for incidence, and parametric survival models based on a Gompertz distribution for mortality. RESULTS: The study found that people who lived in the most socioeconomically disadvantaged areas had lower probabilities of developing LOP cancers than people in the richest districts. The same pattern for mortality, however, was not significant. CONCLUSIONS: The hypothesis that incidence and mortality of LOP cancers will show a positive social gradient was not confirmed in this study, contradicting the existing literature. This could be explained by the social distribution of risky health behaviours, more frequent in socially advantaged populations.

The oral microbiota: a literature review for updating profesional s in dentistry-Part II / La microbiota oral: una revisión de literatura para la actualización de profesionales en odontología-Parte II

ABSTRACT: In the first part of this literature review, published in October 2019 in this journal, we summarized the conceptual background of the oral microbiota, and the main methods used in microbiology to characterize oral organisms. We also presented the most studied bacteria species in the oral microbiota. In this second part, we will discuss the evidence regarding the biological plausibility linking the oral microbiota dysbiosis and systemic diseases, as well as the main factors and mechanisms suspected in this association.

RESUMEN: En la primera parte de esta revisión de literatura, publicada en esta revista en octubre de 2019, se resumieron los antecedentes conceptuales de la microbiota oral y describieron los principales métodos utilizados en microbiología para caracterizar los microorganismos orales. Asimismo, se presentaron las especies bacterianas mejor estudiadas de la microbiota oral. En esta segunda parte, se explorará la plausibilidad biológica que vincularía la disbiosis de la microbiota oral y las enfermedades sistémicas, así como las características que podrían influenciar la composición de la microbiota oral.

Complex social gradient in life expectancy in Costa Rica: an ecological study with 24-Million person-years follow-up / Complejo gradiente socioeconómico en esperanza de vida en Costa Rica: un estudio ecológico con seguimiento de 24 millones de personas-año

ABSTRACT: The knowledge of Costa Rica's situation regarding the social gradient in mortality is still incomplete. National Electoral Rolls, which included all adult Costa Rican citizens were used. The event was death between 2010 and 2018. The exhaustive final sample included 2,747,616 people for 23,985,602 person-years of follow-up. An ecological study at the electoral district level was performed. A negative social gradient was observed in men and in women, in particular in urban area. A protective effect of rural areas compared to urban areas was revealed in men, but not in women. As a result, in men, the poorest districts of mixed/rural areas had similar life expectancy than the richest districts in urban areas. These results partially contradicted the international literature on socioeconomic inequalities. It demonstrates the importance of studying contexts other than high-income countries to better understand the social inequalities in health worldwide.

RESUMEN: El conocimiento sobre la distribución del gradiente social de la mortalidad en Costa Rica aún no ha sido totalmente comprendido y nuevos estudios pueden confirmar o refutar lo que anteriormente se ha observado. Se utilizaron las listas electorales nacionales, que incluían a todos los ciudadanos costarricenses adultos. El evento fue la muerte entre 2010 y 2018. Siendo la muestra exhaustiva final de 2.747.616 personas para 23.985.602 personas-año de seguimiento. Se realizó un estudio ecológico a nivel de distrito electoral, para caracterizar la situación socioeconómica de cada uno. Se observó un gradiente social negativo en hombres y mujeres, en particular en el área urbana. Se observó un efecto protector de las áreas rurales en comparación con las áreas urbanas en los hombres, pero no en las mujeres. Como resultado, en los hombres, los distritos más pobres de las áreas mixtas/rurales tenían una esperanza de vida similar a la de los distritos más ricos de las áreas urbanas. Estos resultados contradicen parcialmente la literatura internacional sobre las inequidades socioeconómicas en mortalidad. Demuestra la importancia de estudiar contextos distintos a los de los países de ingresos altos para comprender mejor las desigualdades sociales en salud en todo el mundo.