Sócrates Aedo

Obesity and its relation to depressive symptoms and sedentary lifestyle in middle-aged women

BACKGROUND The prevalence of obesity increases during female mid-life and although many factors have been identified, data from Latin America is lacking. OBJECTIVE To assess factors related to obesity among middle-aged women and determine the association with depressive symptoms, sedentary lifestyle and other factors. METHODS A total of 6079 women aged 40-59 years of 11 Latin American countries were asked to fill out the Goldberg Anxiety and Depression Scale, the Menopause Rating Scale, the Athens Insomnia Scale, the Pittsburgh Sleep Quality Index and a general questionnaire containing personal socio-demographic data, anthropometric measures and lifestyle information. Obesity was defined as a body mass index (BMI) ≥30 kg/m(2). RESULTS Obesity was observed in 18.5% and sedentary lifestyle in 63.9%. A 55.5% presented vasomotor symptoms, 12.2% had severe menopausal symptoms and 13.2% used hormone therapy for the menopause. Prevalence of depressive symptoms was 46.5% and anxiety 59.7%. Our logistic regression model found that significant factors associated to obesity included: arterial hypertension (OR: 1.87), depressive symptoms (OR: 1.57), sedentary lifestyle (OR: 1.50) diabetes mellitus (OR: 1.34), higher number of individuals living at home (OR: 1.31), sleep problems (OR:1.22), anxiety (OR: 1.21), having a stable partner (OR: 1.20), parity (OR: 1.16) and vasomotor symptoms (OR:1.14). A lower risk for obesity was found among women using hormonal contraceptives (OR: 0.69). CONCLUSION Obesity in middle-aged women is the consequence of the interaction of multiple factors. It was associated to hypertension, depressive symptoms, sedentary lifestyle, climacteric symptoms and other factors.

Sedentary lifestyle in middle-aged women is associated with severe menopausal symptoms and obesity

Objective:The aim of the study was to evaluate the association between sedentary lifestyle and the severity of menopausal symptoms and obesity in middle-aged women. Methods:The Menopause Rating Scale, the Goldberg Anxiety and Depression Scale, and the Athens Insomnia Scale were administered to 6,079 Latin American women aged 40 to 59 years. Sedentary lifestyle was defined as fewer than three weekly, 30-minute periods of physical activity. Results:Sedentary women had more severe menopausal symptoms (total Menopause Rating Scale score: 9.57 ± 6.71 vs 8.01 ± 6.27 points, P < 0.0001) and more depressive symptoms (Goldberg), anxiety (Goldberg), and insomnia (Athens Scale) compared with non-sedentary women. They also had greater mean waist circumference (86.2 ± 12.3 vs 84.3 ± 1.8 cm, P < 0.0001) and a higher prevalence of obesity (20.9% vs 14.3%, P < 0.0001). Logistic regression analysis showed that both obesity (odds ratio [OR] 1.52; 95% CI, 1.32-1.76) and severe menopausal symptoms (OR 1.28; 95% CI, 1.06-1.53), including insomnia and depressive mood, were positively associated with a sedentary lifestyle. Having a stable partner (OR 0.85; 95% CI, 0.76-0.96), using hormone therapy (OR 0.75; 95% CI, 0.64-0.87) and having a higher educational level (OR 0.66; 95% CI, 0.60-0.74) were negatively related to sedentary lifestyle. Conclusions:There was a high prevalence of sedentary lifestyle in this middle-aged Latin American female sample which was associated with more severe menopausal symptoms and obesity.

Netrin-1 acts as a non-canonical angiogenic factor produced by human Wharton’s jelly mesenchymal stem cells (WJ-MSC)

BackgroundAngiogenesis, the process in which new blood vessels are formed from preexisting ones, is highly dependent on the presence of classical angiogenic factors. Recent evidence suggests that axonal guidance proteins and their receptors can also act as angiogenic regulators. Netrin, a family of laminin-like proteins, specifically Netrin-1 and 4, act via DCC/Neogenin-1 and UNC5 class of receptors to promote or inhibit angiogenesis, depending on the physiological context.MethodsMesenchymal stem cells secrete a broad set of classical angiogenic factors. However, little is known about the expression of non-canonical angiogenic factors such as Netrin-1. The aim was to characterize the possible secretion of Netrin ligands by Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC). We evaluated if Netrin-1 presence in the conditioned media from these cells was capable of inducing angiogenesis both in vitro and in vivo, using human umbilical vein endothelial cells (HUVEC) and chicken chorioallantoic membrane (CAM), respectively. In addition, we investigated if the RhoA/ROCK pathway is responsible for the integration of Netrin signaling to control vessel formation.ResultsThe paracrine angiogenic effect of the WJ-MSC-conditioned media is mediated at least in part by Netrin-1 given that pharmacological blockage of Netrin-1 in WJ-MSC resulted in diminished angiogenesis on HUVEC. When HUVEC were stimulated with exogenous Netrin-1 assayed at physiological concentrations (10–200 ng/mL), endothelial vascular migration occurred in a concentration-dependent manner. In line with our determination of Netrin-1 present in WJ-MSC-conditioned media we were able to obtain endothelial tubule formation even in the pg/mL range. Through CAM assays we validated that WJ-MSC-secreted Netrin-1 promotes an increased angiogenesis in vivo. Netrin-1, secreted by WJ-MSC, might mediate its angiogenic effect through specific cell surface receptors on the endothelium, such as UNC5b and/or integrin α6β1, expressed in HUVEC. However, the angiogenic response of Netrin-1 seems not to be mediated through the RhoA/ROCK pathway.ConclusionsThus, here we show that stromal production of Netrin-1 is a critical component of the vascular regulatory machinery. This signaling event may have deep implications in the modulation of several processes related to a number of diseases where angiogenesis plays a key role in vascular homeostasis.

Epigenetic Signatures at the RUNX2-P1 and Sp7 Gene Promoters Control Osteogenic Lineage Commitment of Umbilical Cord-Derived Mesenchymal Stem Cells.

Whartons Jelly mesenchymal stem cells (WJ‐MSCs) are an attractive potential source of multipotent stem cells for bone tissue replacement therapies. However, the molecular mechanisms involved in their osteogenic conversion are poorly understood. Particularly, epigenetic control operating at the promoter regions of the two master regulators of the osteogenic program, RUNX2/P57 and SP7 has not yet been described in WJ‐MSCs. Via quantitative PCR profiling and chromatin immunoprecipitation (ChIP) studies, here we analyze the ability of WJ‐MSCs to engage osteoblast lineage. In undifferentiated WJ‐MSCs, RUNX2/P57 P1, and SP7 promoters are found deprived of significant levels of the histone post‐translational marks that are normally associated with transcriptionally active genes (H3ac, H3K27ac, and H3K4me3). Moreover, the RUNX2 P1 promoter lacks two relevant histone repressive marks (H3K9me3 and H3K27me3). Importantly, RUNX2 P1 promoter is found highly enriched in the H3K4me1 mark, which has been shown recently to mediate gene repression of key regulatory genes. Upon induction of WJ‐MSCs osteogenic differentiation, we found that RUNX2/P57, but not SP7 gene expression is strongly activated, in a process that is accompanied by enrichment of activating histone marks (H3K4me3, H3ac, and H3K27ac) at the P1 promoter region. Histone mark analysis showed that SP7 gene promoter is robustly enriched in epigenetic repressive marks that may explain its poor transcriptional response to osteoblast differentiating media. Together, these results point to critical regulatory steps during epigenetic control of WJ‐MSCs osteogenic lineage commitment that are relevant for future applications in regenerative medicine. J. Cell. Physiol. 232: 2519–2527, 2017.

Quality of life in climacteric Chilean women treated with low-dose estrogen.

OBJECTIVES To evaluate the impact of low-dose oral estrogen therapy on the health-related quality of life (HRQoL) in 45-64-year-old women from the East Metropolitan Health Service (SSMO) in Santiago, Chile. MATERIAL AND METHODS We conducted an observational cross-sectional study. A random population sample of women between 45 and 64 years of age was obtained through an invitation to contact one of 15 primary health care centers of the SSMO of Santiago, Chile. Out of the 927 women who were originally contacted, 844 women were able to complete the Menopausal Rating Scale (MRS) questionnaire. Information about demographic parameters, health issues, and modality of hormonal therapy (HT) were registered. Three groups were compared: group 1 (n=647; non-users of HT), group 2 (n=82; users of low-dose oral estrogen HT), and group 3 (n=115; users of non low-dose estrogens HT). RESULTS There were no differences among groups in terms of demographic and health issue parameters. The results of the MRS scores (total score and somatic, psychological and urogenital domain scores) showed significant differences across the 3 study groups, with more favorable results for HRQoL in groups 2 and 3 (p<0.01 for total, somatic, and psychological scores; p=0.05 for urogenital score). CONCLUSION Climacteric women in the 45-64 age range using HT were shown to have a more favorable impact on HRQoL than non-HT users. Women using low-dose oral estrogen HT had a positive effect on HRQoL, similar to that obtained using non low-dose estrogen regimens.

Efecto diferencial sobre el IGF-1 sérico de tibolona (5 mg/día) vs combinado continuo de estrógeno/progestina en mujeres postmenopáusicas

: postmeno-pausal women, aged 45 to 60 years old, receiving estradiol valerate and medroxyprogesterone wereincluded in the study. After a two months wash out period, in a double blind fashion, they were ran-domly assigned to oral tibolone 5 mg/day or equine conjugated estrogens 0.625 mg + medroxiproges-terone acetate 2.5 mg/day (ECE/MPA). At baseline, 30 and 45 days of treatment, fasting serum osteo-calcin, somatomedin C (IGF-1, insulin-like growth factor 1), growth hormone (GH), and folliclestimulating hormone and first morning urine calcium and creatinine were measured.

Women's Health Initiative estrogen plus progestin clinical trial: a study that does not allow establishing relevant clinical risks.

Objective:This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Womens Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention. Methods:Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome. Results:Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, −2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, −0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, −2.73 days (95% CI, −5.32 to −0.13) for colorectal cancer, and −2.77 days (95% CI, −5.44 to −0.1) for hip fracture. Conclusions:The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.

Agentes causantes de bacteriemia en niños con cáncer y neutropenia febril de alto riesgo en seis hospitales de Santiago, Chile, período 2004-2009

Introduccion: Conocer la etiologia de los episodios de neutropenia febril de alto riesgo (NFAR) en pacientes con cancer tiene importancia para implementar tratamientos antimicrobianos ajustados a la epidemiologia local, lo que tiene impacto en la morbilidad y mortalidad. Objetivo: Describir la etiologia de las bacteriemias en ninos con cancer y NFAR en el periodo 2004-2009, en la red PINDA de Santiago (Region Metropolitana), Chile, y comparar estos agentes y su susceptibilidad antimicrobiana con un estudio previo realizado en el periodo 1994-1998. Material y Metodos: Se registraron prospectivamente los agentes causantes de bacteriemia y su susceptibilidad a antimicrobianos de los pacientes bajo 18 anos de edad en tratamiento quimioterapico por cancer, ingresados con diagnostico de NFAR a los seis hospitales de la red, durante el periodo 2004-2009. Resultados: De 839 episodios de NFAR, 181 tuvieron hemocultivos positivos, correspondientes a cocaceas grampositivas (56%), bacilos gramnegativos (42%) y levaduras (2%). Los agentes mas frecuentemente aislados fueron: Staphylococcus coagula-sa negativa (25%), Escherichia coli (20%), Streptococcus grupo viridans (14%), Staphylococcus aureus (13%) y Pseudomonas spp (9%). Al comparar los dos periodos de tiempo, destacan los siguientes cambios significativos: disminucion en frecuencia relativa de Staphylococcus coagulasa negativa (desde 44 a 25%), aumento de Streptococcus spp (desde 4 a 17%), y aumento de la resistencia de Staphylococcus coagulasa negativa a oxacilina (desde 55 a 77%). Conclusiones: Se dan a conocer los principales agentes etiologicos de los episodios de NFAR y la susceptibilidad a antimicrobianos en un periodo de cinco anos. Esto permite racionalizar el manejo antimicrobiano empirico de los episodios de NFAR en esta poblacion.

Sertraline improves the somatic and psychological symptoms of the climacteric syndrome

ABSTRACT Objective To evaluate the efficacy of sertraline versus placebo in the management of somatic and psychological complaints of the climacteric syndrome. Methods We conducted a randomized, double-blind, placebo-controlled trial. A total of 44 women with moderate to severe complaints, defined as 16 or more points according to the Menopause Rating Scale (MRS) considering only the psychological and somatic domains, were incorporated into the trial and randomized to receive either sertraline (50 mg/day) or placebo. Both groups were evaluated at baseline and after 45 and 90 days of treatment. A reduction of 50% or more in the score was considered as a successful response. Results Thirty-three patients finished the trial (16 in the sertraline group and 17 in the placebo group), showing an odds ratio of 7.94 (95% confidence interval 1.3–57.3), p = 0.0038 for the sertraline group, in spite of the prominent effect of placebo. Conclusions Sertraline was more effective than placebo in the management of the somatic and psychological complaints of the climacteric syndrome.

Risk factors of long-term mortality in middle-aged women: a 27-year follow-up cohort

Abstract Objective: This study aimed to evaluate the impact of different risk factors on long-term mortality in middle-aged women. Methods: Women who received preventive health care control between 1990 and 1993 were recruited. Anamnesis and physical examination were recorded. Blood samples for the measurement of glycemia and lipids were taken. Data are reported as of December 2017. Results: We studied 1197 women aged between 40 and 60 years. We observed 183 deaths (survival 84.0%; 95% confidence interval [CI], 81.7–86.1, Kaplan–Meier survival analysis). The main causes of death were cancer (39.9%; 95% CI, 32.7–47.1), cardiovascular disease (22.9%; 95% CI, 16.8–29.1), infectious disease (13.7%; 95% CI, 8.6–18.7), other causes (7.1%, 95% CI, 3.4–10.9), and unspecified cause (6.6%; 95% CI, 2.9–10.2). The final Cox regression model showed the following hazard ratios for mortality: diabetes mellitus 2.51 (95% CI, 1.40–4.51), history of fracture 2.47 (95% CI, 1.15–5.30), history of heart illness 2.06 (95% CI, 1.15–3.72), arterial hypertension 1.51 (95% CI, 1.08–2.11), age 1.07 (95% CI, 1.04–1.10), body mass index 1.06 (95% CI, 1.02–1.09), and sexual intercourse 0.94 (95% CI, 0.89–0.98). Lipid disorders did not reach statistical significance as a risk factor. Conclusion: Diabetes, a history of fractures, and cardiovascular risk factors, except lipids, are markers of long-term mortality in middle-aged women. Physicians should pay special attention to these risk factors.