Impact of Bariatric Surgery on Circulating Metabolites and Cognitive Performance.

INTRODUCTION: Bariatric surgery is an effective intervention to reduce obesity and improve associated comorbidities. However, its effects on cognitive function are still the subject of debate. Given that the bioavailability of circulating metabolites can influence brain metabolism and cognitive performance, we aimed to assess the effects of bariatric surgery on plasma metabolic profiles and cognitive performance. METHODS: We recruited 26 women undergoing gastric bypass surgery. We conducted anthropometric assessments and collected plasma samples for metabolomic analysis. A set of 4 cognitive tests were used to evaluate cognitive performance. Participants were reevaluated 1 year post-surgery. RESULTS: After surgery, attention capacity and executive function were improved, while immediate memory had deteriorated. Regarding metabolic profile, reduction of beta-tocopherol and increase of serine, glutamic acid, butanoic acid, and glycolic acid were observed. To better understand the relationship between cognitive function and metabolites, a cluster analysis was conducted to identify more homogeneous subgroups based on the cognitive performance. We identified cluster 1, which did not show changes in cognitive performance after surgery, and cluster 2, which showed improved attention and executive function, but reduced performance in the immediate memory test. Thus, cluster 2 was more homogeneous group that replicated the results of non-clustered subjects. Analysis of the metabolic profile of cluster 2 confirmed serine, glutamic acid, and glycolic acid as potential metabolites associated with cognitive performance. CONCLUSIONS: Metabolites identified in this study have potential for biomarkers and alternative therapeutic target to prevent obesity-related cognitive decline. KEY POINTS: • Attention capacity and executive function were improved 12 months post bariatric surgery. • Immediate memory was worsened 12 months post bariatric surgery. • Serine, glutamic acid, and glycolic acid are potential metabolites linked to the alteration of cognitive performance.

Beneficial Short-Term Effects of Bariatric Surgery on Nutritional Inflammatory Profile and Metabolic Biomarkers.

PURPOSE: Bariatric surgery (BS) has several potential metabolic benefits. However, little is known about its impact on changes in the inflammatory potential of diet and its effect on inflammatory and metabolic markers. This study aimed to assess the short-term beneficial effects of BS on dietary inflammatory potential and inflammatory and metabolic markers. MATERIALS AND METHODS: Participants (n = 20) were evaluated 3 months before and after BS. Body mass, body mass index, anthropometric measurements, fat mass, fat-free mass, visceral fat, skeletal muscle mass, basal metabolic rate, serum lipids, HOMA-IR, QUICKI and inflammatory markers, including leptin, adiponectin, adiponectin/leptin ratio and plasminogen activator inhibitor-1 (PAI-1), were evaluated. Diet data were collected using a 3-day diet record and the dietary inflammatory index (DII®) and energy-adjusted dietary inflammatory index (E-DIITM) scores were computed. RESULTS: There was a reduction in DII® (2.56 vs 2.13) and E-DIITM (2.18 vs 0.45) indicating an improvement in inflammatory nutritional profile. Moreover, there were increases in the adiponectin/leptin ratio (0.08 vs 0.21) and QUICKI scores (0.31 vs 0.37), and reductions in leptin (36.66 vs 11.41 ng/ml) and HOMA-IR scores (3.93 vs 1.50). There were also improvements in body composition and anthropometric parameters. CONCLUSIONS: BS promotes changes in metabolic profile, inflammatory state and food intake and these modifications appeared to be associated with improvements in diet-related inflammation, an increase in the adiponectin/leptin ratio and a reduction in leptin. These results contribute to knowledge on the contribution bariatric surgery can make to the treatment of obesity and the reduction of related comorbidities.

Sleep deprivation modulates APOE and LDL receptor-related protein 1 through thyroid hormone T4 and impairs Aß clearance in hippocampus of rats.

Alzheimer's disease is the most common form of dementia. One of its pathological hallmarks is Aß accumulation, which is influenced by APOE genotype and expression, as well as by sleep homeostasis. However, conflicting mechanisms for APOE roles in Aß clearance have been reported, and the relationship between APOE and sleep also remains unclear. In this study, we aimed to investigate how hormonal alteration caused by sleep deprivation affects APOE and its receptors in rats, and to evaluate the role of different cell types in Aß clearance. Paradoxical sleep deprivation for 96 h increased Aß level in hippocampus with concomitant reduction of APOE and LRP1 at the time point within the resting period. Sleep deprivation also significantly reduced T4 levels in both active and resting times. To evaluate the effect of T4 variation, C6 glial cells and primary brain endothelial cells were treated with T4. High T4 level (300 ng/mL) increased APOE, but reduced LRP1 and LDL-R in C6 cells, while in primary endothelial cells, LDL-R levels were increased. Treatment of C6 cells with exogenous APOE reduced LRP1 and Aß uptake. These results suggest that T4 modulates LRP1 and LDL-R in both cell types, but in the opposite manner, thus, sleep deprivation might modify the ratio of the receptors in blood-brain barrier and glial cells by altering T4 levels. Considering that LRP1 and LDL-R are important for Aß clearance, sleep deprivation might also affect the degree of participation of glia in Aß clearance, and consequently, turnover of Aß in the brain.

Severe Obesity in Women Can Lead to Worse Memory Function and Iron Dyshomeostasis Compared to Lower Grade Obesity.

Objective: Obesity is one of the modifiable risk factors for dementia. Insulin resistance, the abundance of advanced glycated end-products, and inflammation are some of the mechanisms associated with the lower cognitive performance observed in obesity. This study aims to evaluate the cognitive function of subjects with distinct degrees of obesity, comparing class I and II obesity (OBI/II) to class III obesity (OBIII), and to investigate metabolic markers that can distinguish OBIII from OBI/II. Study Design. This is a cross-sectional study, in which 45 females with BMI varying from 32.8 to 51.9 kg/m2 completed a set of 4 cognitive tests (verbal paired-associate test, stroop color, digit span, and Toulouse-Pieron cancellation test) and their plasma metabolites, enzymes, and hormones related to glycemia, dyslipidemia, and liver function, as well as the biomarkers of iron status, were concomitantly analyzed. Results: OBIII showed lower scores in the verbal paired-associate test compared to OBI/II. In other cognitive tests, both groups showed similar performance. OBIII presented a lower iron status compared to OBI/II based on total iron binding capacity, degree of transferrin saturation, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. The levels of indicators for glycemia, liver function, and lipid metabolism were similar in both groups. Analysis of plasma metabolites showed that OBIII had lower levels of pyroglutamic acid, myoinositol, and aspartic acid and higher levels of D-ribose than OBI/II. Conclusion: Iron is an essential micronutrient for several metabolic pathways. Thus, iron dyshomeostasis observed in severe obesity may aggravate the cognitive impairment by altering metabolic homeostasis and enhancing oxidative stress. These findings can contribute to searching for biomarkers that indicate cognitive performance in the population with obesity.

Iron-deficient diet induces distinct protein profile related to energy metabolism in the striatum and hippocampus of adult rats.

Iron deficiency is a public health problem that affects all age groups. Its main consequence is anemia, but it can also affect cognitive functions. Although the negative effects of iron deficiency on cognitive function have been extensively described, the underlying mechanism has not been fully investigated. Thus, to gain an unbiased insight into the effects of iron deficiency (ID) on discrete brain regions, we performed a proteomic analysis of the striatum and hippocampus of adult rats subjected to an iron restricted (IR) diets for 30 days. We found that an IR diet caused major alterations in proteins related to glycolysis and lipid catabolism in the striatum. In the hippocampus, a larger portion of proteins related to oxidative phosphorylation and neurodegenerative diseases were altered. These alterations in the striatum and hippocampus occurred without a reduction in local iron levels, although there was a drastic reduction in liver iron and ferritin. Moreover, the IR group showed higher fasting glycaemia than the control group. These results suggest that brain iron content is preserved during acute iron deficiency, but the alterations of other systemic metabolites such as glucose may trigger distinct metabolic adaptations in each brain region. Abnormal energy metabolism precedes and persists in many neurological disorders. Thus, altered energy metabolism can be one of the mechanisms by which iron deficiency affects cognitive functions.

Histopathological changes and oxidative damage in type I and type II muscle fibers in rats undergoing paradoxical sleep deprivation.

BACKGROUND: previous studies have shown that muscle atrophy is observed after sleep deprivation (SD) protocols; however, the mechanisms responsible are not fully understood. Muscle trophism can be modulated by several factors, including energy balance (positive or negative), nutritional status, oxidative stress, the level of physical activity, and disuse. The metabolic differences that exist in different types of muscle fiber may also be the result of different adaptive responses. To better understand these mechanisms, we evaluated markers of oxidative damage and histopathological changes in different types of muscle fibers in sleep-deprived rats. METHODS: Twenty male Wistar EPM-1 rats were randomly allocated in two groups: a control group (CTL group; n = 10) and a sleep deprived group (SD group; n = 10). The SD group was submitted to continuous paradoxical SD for 96  h; the soleus (type I fibers) and plantar (type II fiber) muscles were analyzed for histopathological changes, trophism, lysosomal activity, and oxidative damage. Oxidative damage was assessed by lipid peroxidation and nuclear labeling of 8-OHdG. RESULTS: The data demonstrated that SD increased the nuclear labeling of 8-OHdG and induced histopathological changes in both muscles, being more evident in the soleus muscle. In the type I fibers there was signs of tissue degeneration, inflammatory infiltrate and tissue edema. Muscle atrophy was observed in both muscles. The concentration of malondialdehyde, and cathepsin L activity only increased in type I fibers after SD. CONCLUSION: These data indicate that the histopathological changes observed after 96 h of SD in the skeletal muscle occur by different processes, according to the type of muscle fiber, with muscles predominantly composed of type I fibers undergoing greater oxidative damage and catabolic activity, as evidenced by a larger increase in 8-OHdG labeling, lipid peroxidation, and lysosomal activity.

Sleep deprivation regulates availability of PrPC and Aß peptides which can impair interaction between PrPC and laminin and neuronal plasticity.

PrPC is a glycoprotein capable to interact with several molecules and mediates diverse signaling pathways. Among numerous ligands, laminin (LN) is known to promote neurite outgrowth and memory consolidation, while amyloid-beta oligomers (Aßo) trigger synaptic dysfunction. In both pathways, mGluR1 is recruited as co-receptor. The involvement of PrPC /mGluR1 in these opposite functions suggests that this complex is a key element in the regulation of synaptic activity. Considering that sleep-wake cycle is important for synaptic homeostasis, we aimed to investigate how sleep deprivation affects the expression of PrPC and its ligands, laminin, Aßo, and mGluR1, a multicomplex that can interfere with neuronal plasticity. To address this question, hippocampi of control (CT) and sleep deprived (SD) C57BL/6 mice were collected at two time points of circadian period (13 hr and 21 hr). We observed that sleep deprivation reduced PrPC and mGluR1 levels with higher effect in active state (21 hr). Sleep deprivation also caused accumulation of Aß peptides in rest period (13 hr), while laminin levels were not affected. In vitro binding assay showed that Aßo can compete with LN for PrPC binding. The influence of Aßo was also observed in neuritogenesis. LN alone promoted longer neurite outgrowth than non-treated cells in both Prnp+/+ and Prnp0/0 genotypes. Aßo alone did not show any effects, but when added together with LN, it attenuated the effects of LN only in Prnp+/+ cells. Altogether, our findings indicate that sleep deprivation regulates the availability of PrPC and Aß peptides, and based on our in vitro assays, these alterations induced by sleep deprivation can negatively affect LN-PrPC interaction, which is known to play roles in neuronal plasticity.

Bacteremia in pediatric patients with hematopoietic stem cell transplantation.

BACKGROUND: This study aimed to describe the incidence, microbiological profile, and risk factors associated with bacteremia in pediatric patients with hematopoietic stem cell transplantation (HSCT). METHODS: A retrospective cohort study was performed on patients under 18 years old who underwent HSCT due to any indication, between January 2012 and January 2017. The patient data were collected from the first 100 days post-HSCT. Bacteremia was defined as the isolation of bacteria from at least one blood culture. The relation between bacteremia and associated risk factors was evaluated using univariate and multivariate analysis. RESULTS: We enrolled a total of 111 pediatric patients who received HSCT during the period of study. The total number of patients who developed at least one episode of bacteremia was 46 (41.4%), and the total number of bacteremia episodes was 62. Rectal swabs were performed in 44 patients to detect prior colonization and this showed that 25% of them were positive, the main pathogen isolated being carbapenem-resistant enterobacteriaceae. The Gram-negative bacteria cases accounted for 60% of 62 events. The main Gram-negative bacteria isolated were Klebsiella pneumoniae and Escherichia coli and the majority were resistant strains. The mortality rate on day +100 for the whole cohort was 18% (n=20). Regarding the patients with bacteremia, the mortality rate on day +100 was 30% (n=14), and the cause of death was related to infection in 10 of them. We did not find any statistically significant risk factor for the development of bacteremia. CONCLUSION: Bacteremia is common after HSCT, and there is a high frequency of resistant Gram-negative infections which is related to high mortality.

Latent tuberculosis infection in patients with autoimmune diseases treated with Infliximab and Etanercept / Infección latente por tuberculosis en pacientes con enfermedades autoinmunes que reciben tratamiento con Infliximab y Etanercept

Introduction: Latent tuberculosis infection (LTI) in patients receiving biological therapies is a reality, but this has not been studied in depth in Colombia. Objective: To determine the prevalence of LTI in patients with autoimmune diseases receiving treatment with Infliximab / Etanercept in a referral health center in Cali, Colombia, between the years 2011-2017. Methodology: A retrospective observational study was conducted. We reviewed the 'Registry of patients exposed to tumor necrosis factor-alpha (TNF-α) antagonist drugs in Fundación Valle del Lili'. Patients diagnosed with a chronic inflammatory disease were included who received treatment with Infliximab, Etanercept, or both and followed at least two years. Design: Retrospective observational study. We reviewed the 'Registry of patients exposed to tumor necrosis factor alpha (TNF-α) antagonist drugs in Fundación Valle del Lili'. Patients diagnosed with a chronic inflammatory disease were included who received treatment with Infliximab, Etanercept or both and followed at least a period of 2 years. Results: We included 82 patients; the median age was 47.5 years (IQR=28-60 years), 76% were female, 2% had intimate contact with tuberculosis, 15% were older than 65 years. The 56% had a diagnosis of rheumatoid arthritis as an indication of therapy, and 2% presented infection by hepatitis C virus. The median PPD was 12 mm (IQR=10-17 mm). The prevalence was 3.8% for LTI. Conclusion: The conversion to LTI shows an important prevalence, so it is convenient to perform a routine follow-up of patients receiving therapies with Infliximab and Etanercept.

Introducción: La infección latente por tuberculosis (ILTB) en pacientes que reciben terapias biológicas es una realidad, pero esto no ha sido estudiado a profundidad en Colombia. Objectivo: Determinar la prevalencia de ILTB en pacientes con enfermedades autoinmunes que reciben tratamiento con Infliximab/Etanercept en una institución de salud de referencia de Cali, Colombia, entre los años 2011-2017. Metodología: Se realizó un estudio observacional retrospectivo. Se revisó el 'Registro de pacientes expuestos a fármacos antagonistas del factor de necrosis tumoral alfa (anti TNF-α) en la Fundación Valle del Lili entre los años 2011 y 2017'. Se incluyeron pacientes con diagnóstico de una enfermedad inflamatoria crónica quienes recibieron tratamiento con Infliximab, Etanercept o ambos y con seguimiento al menos un periodo de 2 años. Resultados: Se incluyeron 82 pacientes; la mediana de edad fue 47,5 años RIC (28-60 años), el 76% fue de sexo femenino, el 2% tuvo contacto íntimo con TB, el 15% era mayor de 65 años. El 56% tenía diagnóstico de artritis reumatoide como indicación de terapia y el 2% presentaba infección por HCV. La mediana de PPD fue 12 mm RIC (10-17 mm). La prevalencia fue del 3,8% para ILTB. Conclusiones: La conversión a ILTB muestra una prevalencia importante, por lo que resulta conveniente la realización de un seguimiento rutinario a los pacientes que reciben terapias con Infliximab y Etanercept.

[Lethality analysis in patients with tuberculosis diagnosis in a high complexity hospital in Cali, Colombia]. / Análisis de letalidad en pacientes con diagnóstico de tuberculosis en un centro de alta complejidad en Cali, Colombia.

Background In 2016 tuberculosis (TB) was considered the ninth leading cause of death worldwide and the leading cause of a single infectious agent, with approximately 1.6 million deaths worldwide and a lethality of 15%. Over 95% of cases and deaths are in developing countries like Colombia. AIM: To describe the sociodemographic and clinical characteristics of patients who died during TB treatment in a high complexity hospital in Cali, Colombia. METHODS: We conducted an analytic retrospective cohort during 2007-2016 in Fundación Valle del Lili. We included patients with TB diagnosis, who died during TB treatment. RESULTS: From 787 patients with TB, 69 died (8.8%). Fifty nine percent were male, the average of age was 51.9 years. There was diagnosis delay in 51% of the patients and 74% presented pulmonary TB. Sixty four percent 64 died in the first 30 days of the TB diagnosis and 61% of the deaths were attributable to TB. Twenty five percent of patients had TB/HIV coinfection. Elderly patients (> 65 years old) were associated with death in the first 30 days of TB diagnosis (p < 0,001). DISCUSSION: The lethality found in this study was higher than expected (8.8%), the majority of patients had serious comorbidities. Elderly patients were associated with early death. The main pathophysiological mechanism of death was septic shock caused by severe tuberculous pneumonia.

Análisis de letalidad en pacientes con diagnóstico de tuberculosis en un centro de alta complejidad en Cali, Colombia / Lethality analysis in patients with tuberculosis diagnosis in a high complexity hospital in Cali, Colombia

Resumen Introducción: En el 2016 la tuberculosis (TBC) fue considerada la novena causa de muerte en el mundo y la primera por un único agente infeccioso, con aproximadamente 1,6 millones de muertes y una letalidad de 15%. Más de 95% de los casos de mortalidad mundial se presentan en países en vía de desarrollo como Colombia. Objetivo: Describir las características sociodemográficas y clínicas de los pacientes que fallecieron durante el tratamiento antituberculoso en un centro de alta complejidad en Cali, Colombia. Métodos: Estudio analítico de cohorte retrospectiva, realizado entre 2007-2016 en la Fundación Valle del Lili. Se incluyeron pacientes con diagnóstico de TBC con seguimiento clínico, que fallecirron por cualquier causa. Resultados: De 787 pacientes diagnosticados con TBC, murieron 69 (8,8%). La mayoría de los fallecidos (59%) fueron hombres, edad promedio de 51,9 años. Hubo retraso diagnóstico en 51% de los pacientes y 75% presentaron TBC pulmonar. El 64% murió en los primeros 30 días posteriores al diagnóstico de TBC y 61% de las muertes fueron atribuibles a TBC. Co-infección TBC e infección por VIH se presentó en 23% de los casos. La edad avanzada (> 65 años) se asoció a muerte en menos de 30 días desde el diagnóstico de TBC (p < 0,001). Discusión: La letalidad encontrada es superior a lo esperado (8,8%); la mayoría de los pacientes fallecidos presentó co-morbilidades graves. La edad avanzada se asoció a muerte temprana. El principal mecanismo fisiopatológico de muerte por TBC en este estudio fue el choque séptico secundario a neumonía grave tuberculosa.

Background In 2016 tuberculosis (TB) was considered the ninth leading cause of death worldwide and the leading cause of a single infectious agent, with approximately 1.6 million deaths worldwide and a lethality of 15%. Over 95% of cases and deaths are in developing countries like Colombia. Aim: To describe the sociodemographic and clinical characteristics of patients who died during TB treatment in a high complexity hospital in Cali, Colombia. Methods: We conducted an analytic retrospective cohort during 2007-2016 in Fundación Valle del Lili. We included patients with TB diagnosis, who died during TB treatment. Results: From 787 patients with TB, 69 died (8.8%). Fifty nine percent were male, the average of age was 51.9 years. There was diagnosis delay in 51% of the patients and 74% presented pulmonary TB. Sixty four percent 64 died in the first 30 days of the TB diagnosis and 61% of the deaths were attributable to TB. Twenty five percent of patients had TB/HIV coinfection. Elderly patients (> 65 years old) were associated with death in the first 30 days of TB diagnosis (p < 0,001). Discussion: The lethality found in this study was higher than expected (8.8%), the majority of patients had serious comorbidities. Elderly patients were associated with early death. The main pathophysiological mechanism of death was septic shock caused by severe tuberculous pneumonia.

Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner.

Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC) and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR) or with normal diet (CTL) for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA) was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological disorders. Our findings show that nutritional iron deficiency produces these molecular alterations in a region-specific manner and provide new insight into the variety of molecular pathways that can lead to distinct neurological symptoms upon iron deficiency. Thus, adequate iron supplementation is essential for brain health and prevention of neurological diseases.

Expression of Tyrosine Hydroxylase is Negatively Regulated Via Prion Protein.

Cellular prion protein (PrP(C)) is a glycoprotein of the plasma membrane that plays pleiotropic functions by interacting with multiple signaling complexes at the cell surface. Recently, a number of studies have reported the involvement of PrP(C) in dopamine metabolism and signaling, including its interactions with tyrosine hydroxylase (TH) and dopamine receptors. However, the outcomes reported by independent studies are still debatable. Therefore in this study, we investigated the effects of PrP(C) on the TH expression during the differentiation of N2a cells with dibutyryl-cAMP, a well-known cAMP analog that activates TH transcription. Upon differentiation, TH was induced with concomitant reduction of PrP(C) at protein level, but not at mRNA level. shRNA-mediated PrP(C) reduction increased the basal level of TH at both mRNA and protein levels without dibutyryl-cAMP treatment. This phenotype was reversed by re-expression of PrP(C). PrP(C) knockdown also potentiated the effect of dibutyryl-cAMP on TH expression. Our findings suggest that PrP(C) has suppressive effects on TH expression. As a consequence, altered PrP(C) functions may affect the regulation of dopamine metabolism and related neurological disorders.

Aprendiendo juntas: experiencia comunitaria en talleres de sexualidad / Learning together: communitary experience in sexuality workshops

Describe el trabajo realizado por Círculo de Mujeres por la Salud en la temática de Sexualidad. Incluye una revisión de los distintos períodos que conforman la trayectoria de 15 años de esta organización de mujeres pobladoras de la comuna de El Bosque. Presenta las visiones que las integrantes del grupo han constituido en torno a la sexxualidad, a la metodología con que abordan su trabajo educativo dirigido a adolescentes y mujeres adultas y acerca de como su accionar educativo podría aportar a la constitución de nuevas organizaciones. Se describe la forma en que el grupo se organiza, los contenidos de dos talleres educativos realizados en 1999 y los componentes de su metodología. Las conclusiones dan cuenta de las reflexiones del grupo respecto a los aportes del proceso de sistematización de su experiencia y de los impactos que tiene la participación en actividades educativas orientadas por un enfoque de educación popular, como también , de las dificultades que enfrentan en el abordaje de este tema y de las necesidades de capacitación y recursos para dar continuidad a su trabajo de educación en sexualidad