Inorganic Polyphosphate Affects Biofilm Assembly, Capsule Formation, and Virulence of Hypervirulent ST23 Klebsiella pneumoniae.

The emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains poses a significant threat to public health due to high mortality rates and propensity to cause severe community-acquired infections in healthy individuals. The ability to form biofilms and produce a protective capsule contributes to its enhanced virulence and is a significant challenge to effective antibiotic treatment. Polyphosphate kinase 1 (PPK1) is an enzyme responsible for inorganic polyphosphate synthesis and plays a vital role in regulating various physiological processes in bacteria. In this study, we investigated the impact of polyP metabolism on the biofilm and capsule formation and virulence traits in hvKP using Dictyostelium discoideum amoeba as a model host. We found that the PPK1 null mutant was impaired in biofilm and capsule formation and showed attenuated virulence in D. discoideum compared to the wild-type strain. We performed a proteomic analysis to gain further insights into the underlying molecular mechanism. The results revealed that the PPK1 mutant had a differential expression of proteins involved in capsule synthesis (Wzi-Ugd), biofilm formation (MrkC-D-H), synthesis of the colibactin genotoxin precursor (ClbB), as well as proteins associated with the synthesis and modification of lipid A (ArnB-LpxC-PagP). These proteomic findings corroborate the phenotypic observations and indicate that the PPK1 mutation is associated with impaired biofilm and capsule formation and attenuated virulence in hvKP. Overall, our study highlights the importance of polyP synthesis in regulating extracellular biomolecules and virulence in K. pneumoniae and provides insights into potential therapeutic targets for treating K. pneumoniae infections.

Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer.

CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.

Proteogenomic analysis in an early onset diffuse gastric cancer patient revealed alterations in PIK3R1, TP53, SMAD4 and a potential role of the PI3K-AKT and EGFR pathways: a case report.

Background: Early-onset gastric cancers (EOGC) are poor prognosis hard-to treat malignancies that affect young individuals (<45 years old). Case Description: Herein we describe the case of a 26-year-old female EOGC patient that initially displayed stable disease after first-line CAPOX plus immunotherapy. However, patient eventually developed progressive disease and was consecutively switched to paclitaxel plus ramucirumab, and palliative irinotecan. In search for therapeutic alternatives a proteo-genomic analysis was performed in a tissue biopsy taken after the first progression. Our analyses found a total of 18 somatic mutations, including TP53 and PIK3R1, and a previously unreported germline alteration in the tumor suppressor SMAD4. Also, our proteomic analysis found 62 proteins previously documented as "enriched in stomach cancer" and AKT/mTOR and EGFR as pathways with therapeutic potential. Unfortunately, the clinical utility of AKT/mTOR inhibitors or EGFR targeted therapies could not be assessed. Conclusions: As explained above EOGC is a growing health concern that affects young individuals. Furthermore, the reported case displayed a poor response to standard therapy including checkpoint inhibitors and chemotherapy despite the presence of biomarkers that predict a favorable outcome. Future studies should adopt alternative approaches to find novel, more effective therapies.

Influencia de factores psicosociales en la adherencia al tratamiento farmacológico antihipertensivo: Resultados de una cohorte del Programa de Salud Cardiovascular de la Región Metropolitana, Chile / Influence of psychosocial factors on adherence to antihypertensive drug therapy: Results from a Cardiovascular Health Program cohort followed in the Metropolitan Region of Santiago, Chile

Background: Inadequate blood pressure control in hypertensive patients remains a persistent health problem in Chile and worldwide. Poor adherence to antihypertensive drug therapy is one of the frequently cited factors. Objectives: To determine the influence of psychosocial factors in the adherence to drug therapy in hypertensive patients followed through a Cardiovascular Health Program (CHP) that provides free access to primary care centers located in the Metropolitan Region of Santiago, Chile. Methods: Cross sectional study. A randomized sample of 513 hypertensive patients (30 to 68 years) was obtained from a universe of 1.484 patients. Adherence to treatment was determined by the Morisky-Green-Levine test. Demographic, socioeconomic and average values of blood pressure were recorded. Validated questionnaires were utilized to assess the patient-physician relationship, awareness of being hypertensive, patient perception of social support, family cohesion, patient self-health assessment and symptoms of emotional stress and depression. Results: The drug therapy adherence was 36.6%, higher in women (38.4% vs 28.9%; p < 0.001). After multivariate analysis, absence of adherence was associated with male gender (OR: 1.76 [95% CI 1.21-2.56]), low education (OR: 1.72 [95% CI 1.18 to 2.53]), inadequate patient-physician relationship (OR: 1.56 [95% CI 1.13 to 2.27]), and high level of emotional stress and depression (OR: 1.93 [95% CI 1.27 to 2.94]). Conclusions: Our study highlights the influence of inadequate patient-physician relation, high level of emotional stress and depression, low education level and income and male gender in the lack of adherence to antihypertensive drug therapy in hypertensive patients followed throughout the CHP.

Estatura, factores de riesgo cardiovascular y riesgo de mortalidad en adultos: Proyecto San Francisco, Chile / Height, an early life predictor of cardiovascular risk factors and mortality in chilean adults: the San Francisco Project cohort study

Antecedentes: Una relación inversa entre estatura y riesgo de mortalidad ha sido establecida en estudios prospectivos de países desarrollados. Sin embargo, dicha asociación prácticamente permanece inexplorada en sociedades latinoamericanas en rápida transición económica y epidemiológica. Diseño: De un universo de 11.600 adultos viviendo en el centro urbano de Mostazal, Chile, se realizó un estudio de cohorte prospectivo de una muestra aleatoria ponderada de 795 sujetos seguidos durante 8 años. Método: Desde 1997 a 1999 se evaluó la estatura (percentiles 50 y 75 por sexo), hipertensión, diabetes, dislipidemia, obesidad, tabaquismo, consumo de alcohol y antecedentes hereditarios de enfermedad cardiovascular. El riesgo relativo de mortalidad por cualquier causa fue estimado a través de modelos de regresión de Cox ajustando por edad, sexo, factores de riesgo, educación e ingreso. Resultados: Se observó una relación inversa entre la estatura adulta y los factores de riesgo cardiovascular. En el modelo completamente ajustado el riesgo de mortalidad por cualquier causa asociado a la estatura fue 0,75 (IC 95 por ciento 0,66 - 0,85; p tendencia <0,001). Los factores de riesgo cardiovascular tradicionales solo explicaron 22 por ciento de la asociación inversa establecida entre estatura y mortalidad. Conclusión: En sociedades en transición económica como Chile, la estatura aparece como un factor de riesgo independiente de mortalidad. En esta cohorte de adultos chilenos, los factores de riesgo cardiovascular tradicionales solo explicaron parcialmente la relación inversa entre estatura y mortalidad.

Background: The inverse relationship between height and mortality risk has been well established in developed countries, but remains practically unexplored in Latin American societies. Setting: Chile, 11,600 adults living in the urban centre of Mostazal. Design: Prospective cohort study of a weighted random sample of 795 subjects followed during 8 years. Methods: Height (percentiles 50 and 75 by sex) along hypertension, diabetes, dyslipidemia, obesity, smoking, alcohol consumption and hereditary cardiovascular disease were assessed at baseline. Relative risks of all-cause mortality with 95% confidence intervals were computed in Cox regression models adjusting for age, gender, cardiovascular risk factors and joint-effects of other socioeconomic measures. Results: A significant inverse relationship between cardiovascular risk factors and height was observed. The risk of all cause mortality was 0.75 (95 percent CI 0.66 - 0.85; p-for trend <0.001) after full adjustments. Traditional cardiovascular risk factors explained only 22 percent of the association for height with mortality risk. Conclusions: In this adult cohort, traditional cardiovascular risk factors only explained partially the inverse relationship between height and all-cause mortality. Similar to developed countries, in economic transitioning societies such as Chile, height is an independent risk factor, likely reflecting different early exposure patterns that influence the health status during the life course.

Early life and adult socioeconomic influences on mortality risk: preliminary report of a 'pauper rich' paradox in a Chilean adult cohort.

PURPOSE: The inverse relationship between early life and adult socioeconomic measures and mortality risk has been well established in developed countries, but remains practically unexplored in Latin American societies. The setting was Chile; the study included 11,600 adults living in the urban center of San Francisco de Mostazal. This was a prospective cohort study of a weighted random sample of 795 subjects followed up during 8 years. METHODS: Education (elementary, high school and college), height (percentiles 50 and 75), and income (population quartiles) were assessed at baseline. Relative risks of all-cause mortality were computed in Cox regression models adjusting for age, gender, body mass index, smoking status, and joint effects of the socioeconomic measures. RESULTS: A graded inverse relationship with all-cause mortality was observed for education (risk: 1.0, 0.67, and 0.30, p for trend < 0.01) and height (risk: 1.0, 0.75, and 0.56, p for trend < 0.01), but not for income (p for trend = 0.94). CONCLUSIONS: These findings suggest a 'pauper rich' paradox in transitioning Latin American economies. Income level does not seem sufficient to improve survival in cohorts exposed to adverse early life influences reflected by education and height.

Razón cintura-estatura: un mejor predictor antropométrico de riesgo cardiovascular y mortalidad en adultos chilenos: nomograma diagnóstico utilizado en el Proyecto San Francisco / Waist to height ratio: a better predictor of cardiovascular risk factors and mortality in Chilean adults: diagnostic nomograms from the San Francisco project

Antecedentes: Medidas antropométricas de adiposidad como índice de masa corporal (IMC), circunferencia de cintura (CC), razón cintura-cadera (RCC) y razón cintura-estatura (RCE) son conocidas por estar asociadas a factores de riesgo metabólico. Sin embargo, es controversial cual de ellas es mejor para predecir riesgo cardiovascular y mortalidad. Método: En este estudio de cohorte prospectivo con una muestra ponderada de 6714 hombres y 6340 mujeres, examinamos la relación entre índices antropométricos de adiposidad, factores de riesgo cardiovascular y mortalidad. Calculamos el área bajo la curva ROC (Receiving Operating Characteristic) evaluando el desempeño de cada índice para detectar hipertensión, diabetes o dislipidemia. El riesgo relativo de mortalidad con intervalos de confianza al95 por ciento (IC95 por ciento) fue calculado utilizando regresión logística controlando por edad y factores de riesgo. Resultados: En hombres, las áreas bajo la curva ROC para detectar uno o más factores de riesgo fueron: IMC 0.75 (0.74-0.77), CC 0.85 (0.84-0.86), RCC 0.80 (0.79-0.81) y RCE 0.90 (0.89-0.91). En mujeres esas áreas fueron 0,72 (0,71-0,74), 0,77 (0,76-0,79), 0,65 (0,63-0,66) y 0,81 (0,80-0,82) respectivamente. Durante 8 años de seguimiento (670 muertes, 362 hombres), el riesgo multivariado de mortalidad para IMC, CC, RCC y RCE fue en hombres 0,81 (0,58-1,10), 1,27 (0,93-1,74), 0,89 (0,66-1,21) y 2,37 (1,61-3,49) respectivamente. En mujeres, el riesgo para IMC, CC, RCC, RCE fue 0,95 (0,70-1,27), 1,35 (1,00-1,85), 1,54 (1,17-2,16), y 1,56 (1,13-2,26) respectivamente. Conclusiones: El ajuste de la CC por la estatura permite predecir con mayor precisión factores de riesgo cardiovascular y mortalidad. Se propone un nomograma para adultos chilenos.

Background: Several obesity anthropometric measures like body-mass-index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are known to be associated with metabolic risk factors. However, it remains controversial which of these markers is better to predict cardiovascular risk factors and mortality. Methods: In this prospective observational study with a weighted random sample of 6714 men and 6340 women (San Francisco de Mostazal, Chile), we examined the relation between obesity anthropometric measures, cardiovascular risk factors and all-cause mortality. We calculated area under curve ROC (Receiving Operating Characteristic) to evaluate performance of anthropometric measures for detecting one or more cardiovascular risk factors. Multivariate risks for mortality were calculated with logistic regression models controlling for age and cardiovascular risk factors. Results: In men, areas under curve ROC for detecting one or more risk factors at the baseline were: BMI 0.85 (0.74-0.77), WC 0.85 (0.84-0.86), WHR 0.80 (0.79-0.81) and WHtR 0.90 (0.89-0.91). In women, these areas were respectively 0,72 (0,71-0,74), 0,77 (0,76-0,79), 0,65 (0,63-0,66) and 0,81 (0,80-0,82). During 8 years of follow-up (670 deaths, 362 men), multivariate risks with 95 percent confidence intervals (95%CI) for BMI, WC, WHR, and WHtR were respectively in men 0,80 (0,58-1,10), 1,27 (0,93-1,74), 0,89 (0,66-1,21) and 2,37 (1,61-3,49). In women, multivariate risks for BMI, WC, WHR and WHtR were respectively 0,95 (0,70-1,27), 1,35 (1,00-1,85), 1,54 (1,17-2,16), and 1,56 (1,13-2,26). Conclusions: In this prospective cohort study, adjusting WC for body height was the best way for predicting cardiovascular risk factors and all-cause mortality in Chilean adults.

Enfermedades músculo esqueléticas en población hipertensa y su asociación con obesidad: un estudio transversal en laRegión Metropolitana, Chile / Musculo and skeletal diseases in hypertensive subjects and their association with obesity: a cross sectional study in the Region Metropolitana, Chile

Antecedentes: Los hipertensos presentan elevada prevalencia de obesidad lo que puede predisponer para el desarrollo de enfermedades músculo-esqueléticas (EME). Actualmente se desconoce la magnitud de estas patologías en población hipertensa chilena. Objetivo: Determinar prevalencia de EME en hipertensos bajo control en el programa de salud cardiovascular de la Región Metropolitana y su posible asociación con obesidad. Método: Estudio transversal en una muestra aleatoria simple (n = 1194 sujetos) a partir del universo (N = 391.129) distribuida en 52 comunas de Santiago. Se registró diagnóstico de EME (CIE10, códigos MM00-99), edad, sexo, presión arterial, índice de masa corporal (IMC), obesidad (IMC ³ 30 kg/m2) y carga psicológica. La asociación con obesidad se exploró a través de regresión logística estimando odds ratio (OR) con intervalos de confianza al 95% (IC95%). Resultados: La prevalencia de EME fue 36,5% (39,9% mujeres y 28,3% hombres, p<0.01). En ambos sexos las patologías más frecuentes fueron lumbago, artrosis de rodilla y artralgias. La asociación de EME y obesidad presentó un OR crudo de 1,09 (1,06-1,19) en hombres y de 1,24 (1,22-1,26) en mujeres; luego de ajuste multivariante el OR fue de 1,19 (1,15-1,23) y 1,49 (1,46-1,52) respectivamente. Conclusiones: Además de la edad, sexo femenino y carga psicológica, la obesidad aparece como un factor de riesgo para EME en población hipertensa. La elevada prevalencia observada enfatiza la necesidad de acentuar el control de peso, incluir el ejercicio físico y brindar acceso a la kinesioterapia en la atención primaria chilena.

Background: Hypertensive subjects frequently are obese, which may lead to development of muscular and skeletal diseases (MSD). There is no data regarding the frequency of this complications in Chile. Aim: to determine the prevalence of MSD in hypertensive subjects being followed by the Cardiovascular Health Program in the Region Metropolitana; to determine the association of MSD to obesity in those subjects. Methods: Cross sectional study using a simple random sample of 1194 subjects from the population of 391,129 hypertensives distributed in 52 municipalities in Santiago, Chile. Diagnosis of MSD was established according to CIE 10 codes MM00-99). Age, sex, blood pressure, body mass index and psychological burden were determined. Obesity was defined as IMC ³ 30 kg/m2). Association of MSD with obesity was explored using logistic regression and OR with 95% confidence intervals (95% CI). Results: The prevalence of obesity was 36.5% (39.0% in women, 28.3% in males, p<0.01). In both sexes, lumbar pain, knee osteoarthritis and joint pain were the most common forms of MSD. OR for the association of MSD and obesity was 1.09 (95% CI 1.06-1.19) in males and 1.24 (1.22-1.26) in females. After multivariate adjustment the respective OR became 1.19 (1.15-1.23) and 1.49 (1.46-1.52). Conclusion: In addition to age, female sex and psychological burden, obesity is an independent risk factor for MSD en hypertensive patients. These findings stress the need for better weight control in hypertensives. Physical exercise and physical therapy should be helpful in the primary care of this population.

Desigualdad educacional y socioeconómica como determinante de mortalidad en Chile: análisis de sobrevida en la cohorte del proyecto San Francisco / Socioeconomic and educational inequities as independent predictors for mortality in a developing country: A cohort study in San Francisco, Chile

Background: The socioeconomic position (SEP) and educational level of individuals have an inverse correlation with mortality in developed societies. Aim To assess in a society undergoing a socioeconomic transition, the mortality risk associated to a low SEP (combination of education and income, scale 0-25 points, reference > 10 points) and low education (education years, reference > 8 years), adjusting for other known risk factors. Material and methods: In this prospective cohort study, a random sample of 920 subjects, living in San Francisco de Mostazal, Chile, aged more than 20years (395 males) was examined for the first time in 1997-1999 and re-examined in 2005-2006. All had information about economic household income and level of education. A Cox regression model was used to evaluate the association between mortality and socioeconomic measures. Results: The crude mortality hazard ratio (HR) was 3.34 (95 percent confidence interval (CI) 2.88-3.87) and 6.05 (95 percent CI 5.04-7.26) for low SEP and low educational level, respectively. After adjusting for age, gender, hypertension, diabetes, dyslipidemia, abdominal obesity, smoking, alcohol intake and family history of cardiovascular disease, the figures were 1.23 (95 percent CI 1.04-1.43) and 1.54 (95 percent CI 1.23-1.85) for low SEP and low educational level, respectively. Conclusions: In a society in socioeconomic transition, low SEP and especially low educational level are risk factors for mortality even after adjusting for known mortality risk factors.

[Socioeconomic and educational inequities as independent predictors for mortality in a developing country: A cohort study in San Francisco, Chile]. / Desigualdad educacional y socioeconómica como determinante de mortalidad en Chile: análisis de sobrevida en la cohorte del proyecto San Francisco.

BACKGROUND: The socioeconomic position (SEP) and educational level of individuals have an inverse correlation with mortality in developed societies. AIM: To assess in a society undergoing a socioeconomic transition, the mortality risk associated to a low SEP (combination of education and income, scale 0-25 points, reference > 10 points) and low education (education years, reference > 8 years), adjusting for other known risk factors. MATERIAL AND METHODS: In this prospective cohort study, a random sample of 920 subjects, living in San Francisco de Mostazal, Chile, aged more than 20 years (395 males) was examined for the first time in 1997-1999 and re-examined in 2005-2006. All had information about economic household income and level of education. A Cox regression model was used to evaluate the association between mortality and socioeconomic measures. RESULTS: The crude mortality hazard ratio (HR) was 3.34 (95% confidence interval (CI) 2.88-3.87) and 6.05 (95% CI 5.04-7.26) for low SEP and low educational level, respectively. After adjusting for age, gender, hypertension, diabetes, dyslipidemia, abdominal obesity, smoking, alcohol intake and family history of cardiovascular disease, the figures were 1.23 (95% CI 1.04-1.43) and 1.54 (95% CI 1.23-1.85) for low SEP and low educational level, respectively. CONCLUSIONS: In a society in socioeconomic transition, low SEP and especially low educational level are risk factors for mortality even after adjusting for known mortality risk factors.

Razón cintura-estatura como un predictor de mortalidad en población chilena: un estudio de 8 años de seguimiento en la cohorte del proyecto San Francisco / Wais-to-height ratio to predict mortality in chilean adults: an 8 year follow-up studies

Antecedentes: Medidas antropométricas de obesidad como el índice de masa corporal (IMC), circunferencia de cintura (CC), razón cintura-cadera (RCC) y razón cintura-estatura (RCE) son conocidas por estar asociadas a factores de riesgo metabólico. Sin embargo, es controversial cuál de ellas es mejor para predecir mortalidad. Método: En este estudio prospectivo observacional, reclutamos 920 adultos sanos (>20 años, 395 hombres, San Francisco de Mostazal, Chile) y examinamos la relación entre medidas antropométricas de obesidad y mortalidad general utilizando puntos de corte población-específicos (IMC≥28 kg/m2 ambos sexos; CC≥92cm hombres, ≥88cm mujeres; RCC≥0,94 hombres, ≥0,84 mujeres y RCE≥0,55 ambos sexos). El riesgo relativo (RR) fue calculado utilizando regresión logística controlando por factores de riesgo cardiovascular convencionales. Además, calculamos el área bajo la curva ROC (Receiving Operating Characteristic) para evaluar el desempeño de cada medida antropométrica para predecir mortalidad. Resultados: Durante 8 años de seguimiento ocurrieron 47 muertes. En hombres, el RR con intervalos de confianza al 95 por ciento (IC95 por ciento) para IMC, CC, RCC y RCE fue 1.21 (0.93-1.58), 2.52 (1.86-3.40), 1.11 (0.86-3.20) y 3.38 (2.31-4.96) respectivamente. En mujeres, el RR fue 0.78 (0.60-1.01), 1.44 (1.07-1.93), 1.54 (1.13-2.10), y 1.56 (1.13-2.26) respectivamente. En hombres, las áreas bajo la curva ROC (IC95 por ciento) fueron: IMC 0.66 (0.65-0.68), CC 0.72 (0.71-0.74), RCC 0.72 (0.71-0.74) y RCE 0.77 (0.75-0.78). En mujeres, estas áreas fueron: 0.59 (0.57-0.61), 0.65 (0.63-0.67), 0.58 (0.56-0.60) y 0.70 (0.68-0.71) respectivamente.

Background: Several obesity anthropometric measures like body-mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are known to be associated with metabolic risk factors. However, it remains controversial which of these markers is better to predict mortality. Methods: In this prospective observational study, we enrolled 920 healthy adults (> years, 395 men, 98.7 percent Chilean-Hispanics living in San Francisco de Mostazal, Chile). We examined the relation between obesity anthropometric measures and all-cause mortality using population-specific cutoffs (BMI ≥28 kg/m2 both genders; WC ≥92 cm men, ≥88 cm women; WHR ≥0,94 men, 0,84 women and WHtR ≥0,55 both genders). Multivariate risks were calculated with logistic regression models controlling for cardiovascular and metabolic risk factors. In addition we calculated area under ROC curve (Receiving Operating Characteristic) to evaluate performance of every anthropometric measure to predict mortality. Results: Forty seven deaths occurred during 8 years of follow-up. In men, multivariate risks with 95 percent CI) for BMI, WC, WHR, and WHtR were respectively 1.21 (0.93-1.58), 2.52 (1.86-3.40), 1.11 (0.86-3.20) and 3.38 (2.31-4.96). In women, multivariate risk were respectively 0.78 (0.60-1.01). 1.44 (1.07-1.93), 1.54 (1.13-2.10), and 1.56 (1.13-2.26). In men, areas under curve ROC (95 percent CI) were BMI 0.66 (0.65-0.68), WC 0.72 (0.71-0.74), WHR 0.72 (0.71-0.74) and WHtR 0.77 (0.75-0.78). In women these areas were respectively 0.59 (0.57-0.61), 0.65 (0.63-0.67), 0.58 (0.56-0.60) and 0.70 (0.68-0.71). Conclusions: In this Chilean-Hispanic cohort WHtR is the most accurate predictor of all-cause mortality in comparison with other anthropometric measures of adiposity.

Mediciones antropométricas y riesgo de sufrir un evento cardiovascular no fatal en población chilena: resultados del proyecto San Francisco / Anthropometric indexes and risk of non-fatal cardiovascular events in a Chilean population: the San Francisco Project

Antecedentes: Varios índices antropométricos (IA) de obesidad han mostrado ser predictores de morbilidad cardiovascular en estudios epidemiológicos internacionales. Objetivo: Evaluar el impacto del índice de masa corporal (IMC), circunferencia de abdomen (CA), razón cintura/cadera (RCC), razón cintura/estatura (RCE) e índice pulso-masa (IPM) sobre el riesgo de sufrir un evento cardiovascular (ECV) en una cohorte de población chilena. Diseño: Estudio longitudinal de 920 personas (edad 39,5 +/- 16,3 años, 382 hombres) que participan en el proyecto San Francisco (PSF). Método: La población fue examinada entre 1997 y 1999 consignándose nivel socioeconómico (NSE), hipertensión arterial (HTA), diabetes, colesterol total, triglicéridos, tabaquismo, IMC > 30 kg/m2, CA > 102 cm en hombres y > 85 cm en mujeres, RCC > 1,00 en hombres y > 0,85 en mujeres, IPM > 1,00 y RCE > 0,53. Análisis de riesgo (RR) con intervalos de confianza al 95 por ciento (IC95 por ciento) y regresión logística mediante procedimiento stepwise. Resultados: Luego de 5,3 +/- 0,3 años de seguimiento se registraron 26 ECV resultando predictores: diabetes RR=4,48 (IC95 por ciento 1,87-10,7); HTA RR=5,16 (IC84 por ciento 2,27-11,71); bajo NSE RR=1,81 (IC95 por ciento 1,38-2,37); IMC RR=2,43 (IC95 por ciento 1,10- 5,37); CA RR=3,10 (IC95 por ciento 1,39-6,91) y RCE RR=6,58 (IC95 por ciento 1,96-22,1). En el análisis multivariado que incluyo con todos los IA controlados por edad y sexo, sólo la RCE fue predictor independiente con riesgo de 3,14 (p<0,01). En el modelo completo que incluyó todos los factores de riesgo analizados, sólo la edad, HTA, diabetes, RCE y bajo NSE predicen un ECV no fatal. Conclusión: En la cohorte de San Francisco la RCE aparece como un predictor simple e independiente de enfermedad cardiovascular con mejor desempeño que otros IA de obesidad. Sin embargo, puntos de corte específicos para población chilena deberían ser determinados y evaluados.

Background: International studies have shown that several obesity related anthropometric indices are associated to increased cardiovascular risk. Aim: To evaluate the risk of non-fatal cardiovascular events associated to body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) , pulse mass index (PMI) and waist-to-height ratio (WHtR) upon cardiovascular risk in a cohort of Chileans subjects. Methods: 920 subjects (age 39.5 +/- 16.3 years, 382 males) from the San Francisco Project were prospectively followed.From 1997 to 1999 we determined the socio-economic status (SES), the presence of hypertension, diabetes, cholesterol, and triglyceride levels, smoking status, obesity (BMI >30 kg/m2 , WC >102 for males and > 85 cm for females, WHR > 1 for males and > 0.85 for females, PMI >1 and WHtR > 0.53). Risk ratios and 95 percent confidence intervals (CI) along with stepwise logistic regression were used to assess statistical significance.Results: 26 cardiovascular events took place within 5.3+/-0.3 years of follow up. Significant predictive values were shown for diabetes (RR=4.8, CI 1.9-10.7), hypertension (RR=5.16, CI 2.27 – 11.7), low SEL(RR=1.81, CI 1.38-2.37), BMI (RR 2.43, CI 1.1-5.37), WC (RR=3.1, CI 1.39-6.91 and WHtR (RR = 6.58, CI 1.96-22.1). Logistic regression analysis indicated that only WHtR remained an independent predictor for cardiovascular events. After a different adjustment model, age, hypertension, diabetes, WHtR and low SES had predictive value for cardiovascular events. Conclusion: WHtR appears to be an independent marker for cardiovascular risk in the San Francisco cohort study. However, specific anthropometric cut-off points for chonic diseases in chilean subjets should be determined and tested.

[Predictors of non fatal cardiovascular events in a Chilean cohort: results of the San Francisco Project]. / Predictores de eventos cardiovasculares no fatales en una comunidad urbana en Chile: experiencia de seguimiento Proyecto San Francisco.

BACKGROUND: The San Francisco Project is a prospective study aiming to determine the most important cardiovascular risk factors in the Chilean population. AIM: To report the results of the San Francisco Project after a mean follow up of five years. MATERIAL AND METHODS: Between 1997 and 1999, 920 subjects (aged 39.5 +/- 16.3 years, 382 males), free of cardiovascular events, were examined to determine their cardiovascular risk factors. The prevalence of risk factors was compared with the Chilean National Health Survey. All non fatal cardiovascular events were registered until 2003. A logistic regression model including gender, obesity, family history, educational level and classical cardiovascular risk factors, was performed to identify independent predictors of cardiovascular events. RESULTS: The prevalence of cardiovascular risk factors in the studied population was similar to that of the Chilean National Health Survey, except for serum lipid levels, that were lower in the latter. The mean follow up was 5.3 +/- 0.3 years (range 4-6 years), and 26 cardiovascular events were registered. The independent predictors of these events were age, with a relative risk (RR) of 4.3 and 95% confidence intervals (CI) of 1.9 to 9.5 (p <0.001), high blood pressure with a RR of 5.2 (95% CI 2.3-11.7, p <0.001), diabetes mellitus with a RR of 4.5 (95% CI 1.9-10.7, p <0.01) and a low socioeconomic level with a RR of 3.5 (95% CI 1.5-7.9, p <0.01). The model did not accept serum lipid levels, smoking and alcohol intake as independent predictors. CONCLUSIONS: In this cohort of Chilean people, the independent predictors of non fatal cardiovascular events were high blood pressure, diabetes mellitus and a low socioeconomic level.

Teoría de la ciencia de Karl R. Popper: el principio de falsación como criterio de objetividad y honestidad científica / Karl Popper's science theory: falsification principle like approach to the objectivity and scientific honesty

El punto de partida para la reflexión sobre una teoría de la ciencia son las teorías científicas. Para Popper las ciencias empíricas son sistemas de teorías; y la lógica del conocicmiento científico, puede describirse como una teoría de teorías, es decir una metateoría. La formulación teórica hipotética del intelecto humano intenta imponer leyes a la naturaleza y no descubrirlas. Así partimos de la base que todo conocimiento, incluso las observaciones, están impregnadas de teoría. Para Popper las teorías son conjeturas, hipótesis generales que permiten explicar fenómenos. Nunca son verdaderas, pero si pueden ser falsadas o refutadas, lo cual debe encaminar al científico a rechazarlas. De esta manera, la honestidad y objetividad científica se revela en la formulación de teorías falsables, que son probadas sin recurrir a estratagemas de inmunización contra el error. Las teorías están en competencia y se eliminan por selección de errores mediante la refutación o falsación a partir de un método de contraste de hipótesis esencialmente deductivo, común a todas las ciencias empíricas, de modo que la inducción como método de verificación de hipótesis no es realmente posible bajo la óptica popperiana. Estos conceptos de la metateoría popperiana son revisados en este artículo.

Capacidad aeróbica, composición corporal y gasto calórico asociado a oxidación de sustratos energéticos durante el ejercicio en mujeres sedentarias con sobrepeso / Changes in body composition associated to oxidation of energetic substrates during exercise in sedentary obese women

Objetivo: Explorar la relación entre el consumo de oxígeno máximo (VO2max), composición corporal y oxidación de ácidos grasos (AG) en mujeres con sobrepeso. Métodos: En una serie consecutiva de 30 mujeres sedentarias se evaluó composición corporal por bio-impedanciometría determinando masa grasa absoluta y porcentual (MG y por ciento MG) masa magra (MM y por ciento MM), circunferencia mayor de abdomen (CMA) e índice de masa corporal (IMC). Todas fueron sometidas a calorimetría indirecta en reposo y ejercicio determinándose el índice metabólico basal (IMB), el VO2max y la oxidación de AG. Se realizó análisis por correlación de Pearson y regresión multivariante, error alfa del 5 por ciento. Resultados: El IMC y el CMA muestran correlaciones directas con el IMB sin ajustar. Cuando éste último es ajustado por unidad de peso corporal se observa una relación inversa, especialmente de la CMA con el IMB (-0,81;p<0.01). Lo mismo ocurre con el VO2max que ajustado por unidad de masa corporal exhibe correlación inversa con el por ciento MG (-0,47;p<0,01), IMC (-0,30;p<0,05) y CMA (-029;p<0,05) manteniendo un correlación directa con el por ciento MM (-0,47;p<0,01) y la oxidación de AG durante el ejercicio (0,30;p<0,05). El IMB está fuertemente determinado por la MM (0,99;p<0,001) y éste último fue el mejor predictor del VO2 max en los modelos multivariantes. Conclusión: Tanto IMB y VO2 max ajustados por unidad de peso sugieren que la obesidad, especialmente abdominal, reduce la capacidad metabólica fuertemente dependiente de una disminución de la MM. Así, ejercicios para aumentar MM provocarían un aumento del IMB mientras ejercicios aeróbicos mejorarían la capacidad oxidativa de AG.