The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas.

Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

Dímeros D e hiperglucemia y mortalidad en COVID-19 en un centro hospitalario de México / D-dimers, hyperglycemia and mortality in COVID-19 in a hospital in Mexico

Resumen Objetivo: Evaluar la asociación entre la concentración de glucosa al ingreso y los niveles circulantes de dímeros D en pacientes hospitalizados por enfermedad por coronavirus 2019 (COVID-19). Pacientes y métodos: Se estudiaron 187 pacientes hospitalizados por COVID-19. Se evaluaron las características bioquímicas, la concentración de glucosa y dímeros D, la gravedad de la enfermedad definida por la presencia de neumonía y/o insuficiencia respiratoria que ameritó ventilación mecánica invasiva (VMI) y la causa del egreso hospitalario. Resultados: La edad promedio de los pacientes fue 52 años, el 68% eran hombres, un 40.8% con obesidad y un 23.5% con hipertensión. Del total de pacientes hospitalizados, el 45.5% presentaba diabetes o hiperglucemia a la admisión. La concentración de proteína C reactiva y de dímeros D (1,134 [646.5-4,135.0] vs. 755 [548.7-1,780.0] ng/ml; p = 0.04] fue superior en pacientes con diabetes e hiperglucemia, en comparación con los pacientes con glucosa normal. Los pacientes que requirieron VMI presentaron también mayor concentración de dímeros D. Se observó una correlación directa entre las concentraciones de glucosa inicial y dímeros D (r: 0.239; p = 0.003). Conclusión: En los pacientes con COVID-19 el estado hiperglucémico se asocia directamente con un incremento de la concentración de dímeros D. Los resultados de este estudio deben conducir a insistir en el control glucémico como estrategia fundamental en los pacientes con COVID-19.

Abstract Objective: To evaluate the association between glucose level at admission and circulating levels of D-dimers in patients hospitalized for coronavirus disease 2019 (COVID-19). Methods: 187 patients hospitalized for COVID-19 were studied. Biochemical characteristics, glucose and D-dimers levels, severity of disease, defined by the presence of pneumonia and/or respiratory failure that required invasive mechanical ventilation (IVM) and the cause of hospital discharge were evaluated. Results: Age was 52 years, 68% were male, 40.8% with obesity and 23.5% with hypertension. Of the total of hospitalized patients, 45.5% had diabetes or hyperglycemia upon admission. Patients with diabetes and/or admission hyperglycemia had higher levels of protein C-reactive and D-dimers [(1134 (646.5-4135.0) vs. 755 (548.7-1780.0) ng/ml, p = 0.04], compared to patients with normal glucose level. Patients who required IMV also had a higher concentration of D-dimers. A correlation between glucose and D-dimers levels was evidenced (r=0.239, p=0.003). Conclusions: In patients with COVID-19, the hyperglycemic state is directly associated with an increase in the concentration of D-dimers and severity of disease. The results of this study should lead to insisting on glycemic control as a fundamental strategy in patients with COVID-19.

Double-task exercise programmes to strengthen cognitive and vascular health in older adults at risk of cognitive decline: protocol for a randomised clinical trial.

INTRODUCTION: Cognitive and physical declines are frequent causes of disability among older adults (OAs) in Mexico that imposes significant burden on the health system and OAs' families. Programmes to prevent or delay OAs' cognitive and physical decline are scarce. METHODS AND ANALYSIS: A double-blind randomised clinical trial will be conducted. The study will aim to evaluate two 24-week double-task (aerobic and cognitive) square-stepping exercise programmes for OAs at risk of cognitive decline-one programme with and another without caregiver participation-and to compare these with an aerobic-balance-stretching exercise programme (control group). 300 OAs (100 per group) affiliated with the Mexican Institute of Social Security (IMSS) between 60 and 65 years of age with self-reported cognitive concerns will participate. They will be stratified by education level and randomly allocated to the groups. The intervention will last 24 weeks, and the effect of each programme will be evaluated 12, 24 and 52 weeks after the intervention. Participants' demographic and clinical characteristics will be collected at baseline. The outcomes will include: (1) general cognitive function; (2) specific cognitive functions; (3) dual-task gait; (4) blood pressure; (5) carotid intima-media thickness; (6) OAs' health-related quality of life; and (7) caregiver burden. The effects of the interventions on each outcome variable will be examined using a repeated-measures analysis of variance (ANOVA), with study groups as the between-subjects variable and time as the within-subject variable. ETHICS AND DISSEMINATION: The study was approved by the IMSS Ethics and Research Committees (registration number: 2018-785-095). All participants will sign a consent form prior to their participation. The study results will be disseminated to the IMSS authorities, healthcare providers and the research community. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04068376).

El perímetro de cuello y su relación con los factores de riesgo cardiometabólico en las mujeres / Neck´s perimeter and its relation with the cardiometabolic risk factors in women

RESUMEN Introducción: El perímetro de cuello en la actualidad es una medida útil asociada de manera significativa a la resistencia a la insulina y al riesgo cardiometabólico. Objetivo: Determinar la relación entre el perímetro de cuello y los factores de riesgo cardiometabólico en mujeres de 45 a 60 años de edad. Métodos: Se realizó un estudio en 270 mujeres aparentemente sanas, de 45 a 60 años de edad. Se tomaron medidas antropométricas como peso corporal, índice de masa corporal, perímetro de cintura, perímetro de cuello y el tejido adiposo visceral por bioimpedancia. Se determinaron niveles séricos de glucosa, perfil lipídico (colesterol, triglicéridos, HDL-colesterol, LDL-colesterol), HbA1c, insulina y proteína C reactiva. Resultados: El índice de masa corporal de las participantes fue de 28,2 ± 4,2. Se encontró que 38,1 por ciento de las mujeres presentaban síndrome metabólico y mayor perímetro de cuello, en comparación con las participantes sin síndrome (36,8 + 2,1 vs 35,1 + 1,6 cm, respectivamente, p< 0,0001). El perímetro de cuello se asoció positivamente con índice de masa corporal (r= 0,690, p= 0,0001), tejido adiposo visceral (r= 0,548, p= 0,0001), circunferencia de Cintura (r= 0,640, p< 0,0001), glucosa (r= 0,251, p= 0,0001), triglicéridos (r= 0,143, p= 0,019), HbA1c (r= 0,160, p= 0,010) y proteína C reactiva (r= 0,342, p= 0,001). Conclusiones: Las mujeres con incremento en el perímetro de cuello presentan un perfil de riesgo cardiometabólico aumentado. La medición del perímetro de cuello representa un método útil y práctico en la predicción del riesgo cardiometabólico(AU)

ABSTRACT Introduction: Neck´s perimeter is nowadays a useful measure significantly associated to insulin resistance and to cardiometabolic risk. Objective: To determine the relation between the neck´s perimeter and the cardiometabolic risk factors in women from 45 to 60 years old. Methods: A study was performed in 270 apparently healthy women, aging 45 to 60 years old. Anthropometric measurements were taken such as weight, body mass index, waist circumference, neck´s perimeter and visceral adipose tissue by bioelectrical impedance analysis. There were identified serum levels of glucose, lipid profile (cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol), HbA1c, insulin and C-reactive protein. Results: The body mass index of the participants was 28.2 ± 4.2. It was found that 38.1 percent of the women had a metabolic syndrome and a higher perimeter of neck, in comparison with participants without the syndrome (36.8 + 2.1 vs 35.1 + 1.6 cm, respectively, p< 0.0001). The neck´s perimeter was positively associated with body mass index (r = 0.690, p= 0.0001), visceral adipose tissue (r = 0.548, p= 0.0001), waist circumference (r = 0.640, p< 0.0001), glucose (r = 0.251, p= 0.0001), triglycerides (r = 0.143, p = 0.019), HbA1c (r = 0.160, p = 0.010) and C-reactive protein (r = 0.342, p = 0.001). Conclusions: Women with an increase in the neck´s perimeter have a profile of increased cardiometabolic risk. The measurement of neck´s perimeter represents a useful and practical method for the prediction of cardiometabolic risk(AU)

Soluble Intercellular Adhesion Molecule-1 (sICAM-1) as a Biomarker of Vascular Cognitive Impairment in Older Adults.

BACKGROUND: Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal. OBJECTIVE: To determine whether sICAM-1 contributes to the prediction of VCI. METHODS: Community-dwelling older adults (n = 172) from the "Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults" (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI. RESULTS: A total of 31 VCI cases were identified. sICAM-1 was higher in VCI (VCI: 450.7 [241.6] ng/mL vs. controls: 296.9 [140.9] ng/mL). sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) were associated with VCI group membership in all models (OR: 6.9, 95% CI: 1.1-42.2). The final saturated model explained 64% of the variance in VCI group membership. CONCLUSION: High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.

[Asociación del estado hormonal con el riesgo cardiovascular evaluado por Globorisk en mujeres mexicanas].

INTRODUCTION: Cardiovascular disease is the main cause of mortality worldwide. In women, its incidence increases at the sixth decade of life, coinciding with postmenopause. Whether this effect is due to menopause-related hormonal changes is not known. OBJECTIVE: To evaluate the differences in cardiovascular risk in pre- and postmenopausal women by means of the Globorisk risk scale, the triglyceride/high-density lipoproteins cholesterol (Tg/HDL-C) ratio and metabolic syndrome (MS) criteria. METHOD: Cross-sectional study that included 408 women from 40 to 60 years of age; anthropometric measurements and biochemical determinations were performed. The participants were classified as premenopausal and postmenopausal. Cardiovascular risk was assessed using the MS criteria, the Globorisk risk calculator and the Tg/HDL-C ratio. RESULTS: Postmenopausal women showed a significant increase in waist circumference, total cholesterol and triglycerides in comparison with premenopausal women. Significant associations were found between hormonal state and Globorisk measured cardiovascular risk (OR = 2.50; 95 % CI = 1.67-3.74) and the Tg/HDL-C ratio (OR = 1.66; 95 % CI = 1.09-2.52). CONCLUSION: Cardiovascular risk factors have a higher prevalence in postmenopause. The Globorisk scale and Tg/HDL-C ratio identify cardiovascular risk in postmenopausal women.

INTRODUCCIÓN: La enfermedad cardiovascular es la principal causa de mortalidad en el mundo. En la mujer se incrementa en la sexta década de la vida, coincidiendo con la posmenopausia. Se desconoce si este efecto se debe a cambios hormonales relacionados con la menopausia. OBJETIVO: Evaluar diferencias del riesgo cardiovascular en mujeres pre y posmenopáusicas mediante la escala de riesgo Globorisk, el índice triglicéridos/c-HDL (Tg/c-HDL) y los criterios de síndrome metabólico (SM). MÉTODOS: Estudio transversal que incluyó a 408 mujeres de 40 a 60 años; se realizaron mediciones antropométricas y bioquímicas. Las participantes se clasificaron en premenopáusicas y posmenopáusicas. El riesgo cardiovascular se evaluó utilizando los criterios de SM, calculadora de riesgo Globorisk y el índice Tg/c-HDL. RESULTADOS: Las mujeres en etapa posmenopáusica presentaron incremento significativo en la circunferencia de cintura, de colesterol total y triglicéridos, en comparación con las mujeres premenopáusicas. Se encontraron asociaciones significativas del estado hormonal con el riesgo cardiovascular evaluado por Globorisk (RM = 2.50, IC 95 % = 1.67-3.74) y con el índice Tg/c-HDL (RM = 1.66, IC 95 % = 1.09-2.52). CONCLUSIÓN: Los factores de riesgo cardiovascular tienen mayor prevalencia en la posmenopausia. La escala Globorisk y el índice Tg/c-HDL identifican el riesgo cardiovascular en la mujer posmenopáusica.

In memory of Dr. Arturo Zárate Treviño, pioneer in the study of gynecological endocrinology in Mexico / In memoriam Dr. Arturo Zárate Treviño, pionero en el estudio de la endocrinología ginecológica en México

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Sin resumen

Relationship between bone remodeling and metabolism in the elderly / Relación entre la actividad ósea y el metabolismo en el adulto mayor

Background: Recent studies have shown that osteocalcin (OC) is related to not only bone metabolism but also energy metabolism. The aim of the present study was to investigate whether OC was associated with metabolic factors and bone mineral density (BMD) in elderly men. Methods: A cross-sectional study was done including 122 healthy men aged 60 years or older. Serum glucose, lipids, insulin, adiponectin and OC were measured and BMD was estimated using dual energy X-ray absorptiometry. Results: 42.8% of men had metabolic syndrome (MetS). OC levels were not significantly different between men with and without MetS. OC concentrations were inversely associated with body mass index (BMI) (r = −0.226, p = 0.04), waist circumference (r = −0.261, p = 0.02), glucose (r = −0.245, p = 0.03), insulin (r = −0.235, p = 0.03), and HOMA-IR (r = −0.211, p = 0.04). In addition, OC levels were higher in patients with diminished BMD compared with those with normal BMD. Conclusions: OC levels correlate negatively with BMI, waist circumference, glucose, insulin and HOMA-IR in elderly men, which suggests a connection between bone and energy metabolism.

Introducción: diversos estudios sugieren que la osteocalcina (OC) contribuye no solo a la regulación del metabolismo óseo, sino también al metabolismo energético. El objetivo del trabajo fue evaluar la relación entre la concentración sérica de OC y los parámetros metabólicos y la densidad mineral ósea (DMO) en adultos mayores. Métodos: estudio transversal descriptivo en 122 hombres sanos mayores de 60 años. Se les determinó glucosa, lípidos, insulina, adiponectina y OC. La DMO se analizó por absorciometría de doble fotón. Resultados: el 42.8% de la muestra presentó síndrome metabólico (SM). Los niveles de OC no difirieron entre el grupo de pacientes con y sin SM. Se observó una correlación negativa entre la concentración de OC y el índice de masa corporal (IMC) (r = −0.226, p = 0.04), circunferencia de cintura (r = −0.261, p = 0.02), glucosa (r = −0.245, p = 0.03), insulina (r = −0.235, p = 0.03) y HOMA-IR (r = −0.211, p = 0.04). Los pacientes con DMO disminuida mostraron una concentración significativamente mayor de OC en comparación con aquellos con DMO normal. Conclusiones: la OC se asoció inversamente con el IMC, la obesidad abdominal, la glucosa, la insulina y la resistencia a la insulina en hombres mayores de 60 años. Lo anterior confirma la conexión que existe entre el tejido óseo y el metabolismo.

Oxidative stress in the elderly with diabetes mellitus or hypertension / Estrés oxidativo en adultos mayores con diabetes mellitus o hipertensión arterial

Background: Mexico City has the highest aging rate in the country, as well as a high prevalence of diabetes mellitus (DM) and hypertension (HT). It is known that each one of these conditions increase oxidative stress (OS) independently. Methods: With this study we described changes in OS of 18 patients without DM or HT (controls), 12 with DM, 23 with HT, and 18 with DM and HT, all of them members of the COSFAMM (Cohorte de Obesidad, Sarcopenia y Fragilidad en Adultos Mayores de México). OS was measured by the quantification of reactive oxygen species (ROS), by the oxidation of diclorofluorosceine, and by determination of lipid peroxidation by product malondialdehyde (MDA). Results: HT patients showed increased ROS levels, as did men with HT compared with the respective DM and HT groups. Also, women of control group showed higher levels of ROS compared with men. Conclusions: Generally, HT turned out to be the most influential factor for the increase of oxidative stress in the elderly while DM has no effect whatsoever.

Introducción: la Ciudad de México tiene el mayor índice de envejecimiento del país, así como una alta prevalencia de diabetes mellitus (DM) e hipertensión arterial (HTA). Se sabe que cada una de estas condiciones incrementa el estrés oxidativo (EO) de forma independiente. Métodos: en este estudio describimos los cambios en el EO de 18 pacientes sin DM ni HTA (controles), 12 con DM, 23 con HTA y 18 con DM y HTA, todos miembros de la Cohorte de Obesidad, Sarcopenia y Fragilidad en Adultos Mayores de México (COSFAMM). El EO fue medido por la cuantificación de especies reactivas de oxígeno (ERO) por la oxidación de la diclorofluorosceína (DCFH) y por determinación de peroxidación de lípidos por producto malondialdehído (MDA). Resultados: los pacientes con HTA mostraron niveles de ERO elevados, así como los hombres con HTA, comparados con los grupos correspondientes de DM y HTA. Asimismo, las mujeres del grupo control mostraron mayor cantidad de ERO que los hombres. Conclusiones: en general, la HTA en el adulto mayor resultó ser el factor que mayor contribución tiene en el incremento del estrés oxidativo, mientras que la DM no tiene efecto alguno.

An increase in epicardial fat in women is associated with thrombotic risk. / El incremento de la grasa epicárdica en mujeres se asocia a riesgo trombótico.

INTRODUCTION: A decrease in fibrinolytic activity and an increase in the thickness of the epicardial adipose tissue have been observed in patients with coronary artery disease. The aim of this study was to determine the association between epicardial adipose tissue and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). METHODS: A cross-sectional study was conducted on 56 apparently healthy women aged 45 to 60 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Epicardial thickness was assessed by transthoracic echocardiography. RESULTS: The concentration of PAI-1 was directly associated with the thickness of the epicardial adipose tissue (r=0.475, P=.001), body mass index (BMI), visceral adipose tissue, insulin resistance, glucose, and HDL-cholesterol. The multivariate regression analysis indicated that epicardial fat independently predicts the concentrations of PAI-1. CONCLUSIONS: Women with thicker epicardial adipose tissue have reduced fibrinolytic activity, and consequently greater thrombotic risk.

Menopausal women have hypofibrinolysis even in subclinical stage of atherosclerosis.

BACKGROUND: PAI-1 is the main inhibitor of fibrinolysis. Increase in PAI-1 levels has been associated with the risk of coronary disease; however, there are few studies on the relationship between subclinical atherosclerosis and PAI-1 levels. OBJECTIVE: The aim of this study was to analyze the relationship between PAI-1 level and carotid intima-media thickness in premenopausal and postmenopausal women without apparent cardiovascular disease. MATERIAL AND METHODS: A cross-sectional study was conducted in 142 women aged 45 to 60 years with no history of cardiovascular disease. Anthropometric and laboratory measurements were performed, including PAI-1 levels. All participants underwent a B-Mode ultrasound to measure intima-media thickness. Subclinical atherosclerosis was considered when intima-media thickness was ≥ 0.7 mm and/or an atheromatous plaque was observed. RESULTS: Postmenopausal women had greater intima-media thickness than premenopausal women (0.688 ± 0.129 vs. 0.621 ± 0.113 mm; p < 0.05). Compared to women with normal intima-media thickness, women with subclinical atherosclerosis had higher PAI-1 levels (23.2 ± 13.7 vs. 30.4 ± 20.7 ng/ml; p < 0.05). In all participants, intima-media thickness correlated with PAI-1 (r = 0.302; p = 0.01) and with age (r = 0.358; p = 0001). CONCLUSIONS: An increase in intima-media thickness was observed in postmenopausal women compared with premenopausal women. Asymptomatic women with increased intima-media thickness had higher PAI-1 levels. These findings suggest that fibrinolytic activity is low in the subclinical stage of atherosclerosis.

Prevalence of anemia and its impact on the state of frailty in elderly people living in the community: SADEM study.

Anemia represents a global health problem that negatively impacts quality of life in elderly population; however, its impact on the geriatric syndrome of frailty is unclear. We examined the prevalence of anemia among elderly and sought a relationship between hemoglobin and the phenotype of frailty. Baseline hemoglobin quintiles and anemia were assessed in relation to frailty status in a prospective study with 1,933 older community-dwelling adults enrolled in the Study on Aging and Dementia in Mexico (SADEM). Logistic regression was used to model the relationship between frailty and Hb, adjusting for risk factors of frailty, sociodemographic data, cognitive decline, chronic diseases, and some risky habits. Prevalence of frailty was 8.3 %. Frailty risk was highest at the lowest hemoglobin quintile (<14.3 g/dL for men; <13.3 g/dL for women), and 160 (8.3 %) were anemic (<13 g/dL for men; <12 g/dL for women). The relationship between frailty and Hb levels, adjusted for age and sex, observed in the first and fifth quintiles, compared with the fourth quintile, were 1.53 (95 % confidence interval (CI), 1.46-1.60) and 1.05 (95 % CI, 1.01-1.15). After multivariate adjustment, the odds ratios (ORs) were 1.23 (95 % CI, 1.17-1.13) and 1.06 (95 % CI, 1.01-1.11). The association was not diminished by risk factors for frailty (body mass index (BMI), comorbidity, cognitive decline, smoking, alcohol consumption, etc.). In community-dwelling older adults, low hemoglobin concentrations and anemia were independently associated with increased frailty risk. This suggests that mild anemia and low Hb levels are independent, modifiable risk factors for frailty.

Epicardial adipose tissue is associated with visceral fat, metabolic syndrome, and insulin resistance in menopausal women.

INTRODUCTION AND OBJECTIVES: Epicardial adipose tissue has been associated with several obesity-related parameters and with insulin resistance. Echocardiographic assessment of this tissue is an easy and reliable marker of cardiometabolic risk. However, there are insufficient studies on the relationship between epicardial fat and insulin resistance during the postmenopausal period, when cardiovascular risk increases in women. The objective of this study was to examine the association between epicardial adipose tissue and visceral adipose tissue, waist circumference, body mass index, and insulin resistance in postmenopausal women. METHODS: A cross sectional study was conducted in 34 postmenopausal women with and without metabolic syndrome. All participants underwent a transthoracic echocardiogram and body composition analysis. RESULTS: A positive correlation was observed between epicardial fat and visceral adipose tissue, body mass index, and waist circumference. The values of these correlations of epicardial fat thickness overlying the aorta-right ventricle were r = 0.505 (P < .003), r = 0.545 (P < .001), and r = 0.515 (P < .003), respectively. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome than in those without this syndrome (mean [standard deviation], 544.2 [122.9] vs 363.6 [162.3] mm(2); P = .03). CONCLUSIONS: Epicardial fat thickness measured by echocardiography was associated with visceral adipose tissue and other obesity parameters. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome. Therefore, echocardiographic assessment of epicardial fat may be a simple and reliable marker of cardiovascular risk in postmenopausal women.

[Historical notes about scientific research in the Instituto Mexicano del Seguro Social.] / Notas históricas sobre la investigación científica en el IMSS.

Medical research in the Instituto Mexicano del Seguro Social has been considered one of the most important in this country for quality and quantity. Thanks to the work and leadership of Benito Coquet, who initiated the building of the National Medical Center in 1961, and the work of two pillars of research, Luis Castelazo and Bernardo Sepúlveda, the Institute successfully improved scientific research. In the years that followed, the Institute fostered the professionalization of research, the creation of research units in different areas of science, the incorporation of consolidated groups of researchers, the relationship with other institutions, the incorporation to the Sistema Nacional de Investigadores, the editing of a journal to expose outside the work done within the Institute, and the formation of a trust to raise funds for financing. Thanks to all that, institutional research strengthened in all lines, and it was placed first, at certain times, at the national level.

La investigación médica del Instituto Mexicano del Seguro Social ha sido considerada una de las más importantes del país. Gracias a la labor del doctor Benito Coquet --en cuya gestión se comenzó en 1961 la edificación del Centro Médico Nacional-- y al trabajo de dos pilares de la investigación, los doctores Bernardo Sepúlveda y Luis Castelazo, el Instituto se orientó a la superación en los servicios de atención, académicos y de investigación. En los años posteriores se impulsó la profesionalización de la investigación, la creación de las unidades de investigación médica en las diferentes áreas de especialización, la incorporación de grupos consolidados, las relaciones interinstitucionales, la incorporación al Sistema Nacional de Investigadores, la edición de una revista que fuera el foro de exposición de los trabajos realizados y la formación de un fideicomiso para la obtención de fondos de financiamiento. Gracias a todo ello se ha podido robustecer la investigación institucional en todos los renglones, para ubicarla en algunas épocas como la primera a nivel nacional.

[Male hormonal profile in workers exposed to toluene in an industrial packaging plant]. / Perfil hormonal masculino de trabajadores expuestos a tolueno en una fábrica de empaques industriales.

OBJECTIVE: to identify changes in the male hormonal profile (MHP), consisting of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone, in workers exposed to toluene. METHODS: cross-sectional study that included 42 workers, formed in two groups: with high and low exposure to toluene (HET and LET, respectively); the hippuric acid in urine, and the serum concentration in FSH, LH, and testosterone were measured. RESULTS: hippuric acid in subjects with LET was 2.53 ± 1.20 g/g creatinine, and with HET: 6.31 ± 3.83 g/g creatinine (p = 0.02). Seric FSH concentration was 5.12 ± 0.77 and 3.55 ± 0.3 mU/mL (p = 0.02) in LET and HET, respectively; LH: 2.66 ± 0.45 and 2.77 ± 0.21 (p = 0.81), and testosterone 3.91 ± 0.34 and 4.86 ± 0.23 ng/mL (p = 0.04). By regression analysis, the correlation coefficient of FSH with hippuric acid was r = -0.33 (p = 0.031), with coefficient of determination of 11 %; the LH correlation coefficient was r = -0.037 (p = 0.88) and 0.05 %, respectively; and the one for testosterone was r = 0.61 (p = 0.0001) and 34 %. CONCLUSIONS: in HET group, FSH and LH serum levels diminished; testosterone shows an opposite response, perhaps explained by a different sensitivity of the male gonads exposed to toluene.

Objetivo: identificar cambios en el perfil hormonal masculino (PHM), integrado por las hormonas luteinizante (LH), folículo-estimulante (FSH) y testosterona, de trabajadores expuestos a tolueno. Métodos: estudio transversal que incluyó a 42 trabajadores. Se constituyeron dos grupos: con exposición alta (EAT) y con exposición baja (EBT) a tolueno. Se midió la concentración sérica de FSH, LH y testosterona, así como el ácido hipúrico en orina. Resultados: ácido hipúrico en sujetos con EBT: 2.53 ± 1.20 g/g creatinina; con EAT: 6.31 ± 3.83 g/g creatinina (p = 0.02). Concentración sérica de FSH: 5.12 ± 0.77 y 3.55 ± 0.3 mU/mL (p = 0.02) en EBT y EAT, respectivamente; de LH: 2.66 ± 0.45 y 2.77 ± 0.21 (p = 0.81); y testosterona: 3.91 ± 0.34 y 4.86 ± 0.23 ng/mL (p = 0.04). Por análisis de regresión, el coeficiente de correlación de FSH con ácido hipúrico fue de r = -0.33 (p = 0.031), con coeficiente de determinación de 11%; el de LH: r = -0.037 (p = 0.88) y 0.05 % respectivamente, y el de testosterona: r = 0.61 (p = 0.0001) y 34 %. Conclusiones: en el grupo EAT, los niveles séricos de la FSH y LH disminuyeron; la testosterona muestra una respuesta contraria, lo cual quizás se explique por una diferente sensibilidad de gónadas masculinas a la exposición del tolueno.

[Oral or trandsdermanl hormone replacement therapy reduces interleukine-6 levels]. / La terapia estrogénica de reemplazo, oral o transdérmica, reduce las concentraciones de interleucina-6.

OBJECTIVE: To compare the effect of oral and transdermal estrogen replacement therapy (ET) on circulating interleukin-6 (IL-6) in post-menopausal women. PATIENTS AND METHOD: Prospective open trial study in 55 healthy hysterectomized postmenopausal women with a mean age of 52 years. Twenty-seven women received oral conjugated equine estrogens (0.625 mg daily) and the remaining 28 received transdermal estrogen replacement therapy (50 microg/day) during 6 months. At baseline both groups were similar as to age, body weight, and body mass index as well as serum levels of LH, FSH, 17-beta estradiol (E2) and IL-6. RESULTS: Baseline elevated IL-6 levels decreased significantly (p<0.05) after both oral and transdermal estrogen replacement therapy; this decrement showed no difference between the two groups. After the follow-up there were no differences in body weight and body mass index between groups; however, in the oral group there was a trend to increment this parameters. Serum levels of E2 and IL-6 were negatively correlated in the two groups and IL-6 was positively correlated with body mass index in untreated women and this correlation was the same in women with estrogen replacement therapy. CONCLUSIONS: The decrement of IL-6 after estrogen replacement therapy was similar for both routes of administration; in addition IL-6 had a negative correlation with E2 and a positive correlation with body mass index.