Abstract: Autophagy is a highly regulated catabolic process that involves sequestration and lysosomal degradation of cytosolic components such as damaged organelles and misfolded proteins. While autophagy can be considered to be a general cellular housekeeping process, it has become clear that it may also play cell type-dependent functional roles. In this study, we analyzed the functional importance of autophagy in human hematopoietic stem/progenitor cells (HSPCs), and how this is regulated during differentiation. Western blot-based analysis of LC3-II and p62 levels, as well as flow cytometry-based autophagic vesicle quantification, demonstrated that umbilical cord blood-derived CD34(+) /CD38(-) immature hematopoietic progenitors show a higher autophagic flux than CD34(+) /CD38(+) progenitors and more differentiated myeloid and erythroid cells. This high autophagic flux was critical for maintaining stem and progenitor function since knockdown of autophagy genes ATG5 or ATG7 resulted in reduced HSPC frequencies in vitro as well as in vivo. The reduction in HSPCs was not due to impaired differentiation, but at least in part due to reduced cell cycle progression and increased apoptosis. This is accompanied by increased expression of p53, proapoptotic genes BAX and PUMA, and the cell cycle inhibitor p21, as well as increased levels of cleaved caspase-3 and reactive oxygen species. Taken together, our data demonstrate that autophagy is an important regulatory mechanism for human HSCs and their progeny, reducing cellular stress and promoting survival. Resumen: La autofagia es un proceso lisosomal catabólico altamente regulado que implica el secuestro y degradación de componentes citosólicos: tales como proteínas mal plegadas y orgánelos deteriorados. Mientras que la autofagia puede ser considerada como un proceso general de limpieza celular, también juega un papel funcional dependiendo del tipo de célula. En el presente estudio, hemos analizado la importancia de la autofagia en las células madre hematopoyéticas y sus progenitores y cómo dicho proceso está regulado durante la diferenciación. El análisis de los niveles de LC3-II y p62, así como la cuantificación de la autofagia mediante citometría de flujo demostraron que los progenitores hematopoyéticos inmaduros CD34 (+) / CD38 (-) tienen un flujo de autofagia mayor que las células eritroides y mieloides. Este alto flujo de autofagia es crucial para las células madre y los progenitores hematopoyéticos inmaduros CD34 (+) / CD38 (-) ya que la disminución en los niveles de ATG7 y ATG5 resulta en una reducción de dichas células tanto in vitro como in vivo. Lo anterior es consecuencia de la inhibición parcial del ciclo celular y de un aumento en apoptosis. Adicionalmente, observamos un incremento en la expresión de p53, los genes pro-apoptosis BAX y PUMA, el inhibidor de ciclo celular p21, los niveles de caspasa-3 clivada y las especies reactivas del oxígeno. En conclusión, nuestros datos demuestran que la autofagia es un mecanismo de regulación importante para las células madre hematopoyéticas y sus progenitores reduciendo los niveles de estrés y promoviendo su supervivencia.

Abstract: OBJECTIVE: To study the prevalence and profile of thyroid disease in a cohort of referred patients with oral lichen planus (OLP) in comparison with a random population sample and to examine the clinical characteristics of OLP patients with and without thyroid disease. STUDY DESIGN: Data from 1611 patients with OLP and 1615 patients from the general population were collected by using a standardized registration method. Patients with OLP using levothyroxine (OLP/levothyroxine+) were re-examined to collect information about existing OLP lesions and to confirm the thyroid disease diagnosis. The clinical characteristics of OLP lesions in this group were compared with those in an age- and gender-matched population of patients with OLP without a history of thyroid disease or levothyroxine medication (OLP/levothyroxine-). RESULTS: Nearly 11% (n = 170) of the patients with OLP were taking levothyroxine compared with 2.5% (n = 40) of the controls (multivariate odds ratio 2.99, 95% confidence interval 2.03-4.44; P < .0001). No difference was found in the thyroid disease profile between the groups. At the time of re-examination, patients with OLP/levothyroxine- displayed more erythematous OLP lesions and complained of more severe symptoms compared with the OLP/levothyroxine+ group (P < .001). CONCLUSION: The prevalence of thyroid disease in patients with OLP was significantly higher than in the general population. The OLP lesions of patients with concomitant thyroid disease have a different presentation over time, which indicates a specific subgroup of OLP." Resumen: OBJETIVO: Estudiar la prevalencia y el perfil de la enfermedad de la tiroides en una cohorte de pacientes remitidos con liquen plano oral (LPO) en comparación con una muestra aleatoria de una, y examinar las características clínicas de pacientes con LPO con y sin enfermedad de la tiroides. DISEÑO DEL ESTUDIO: Datos de 1.611 pacientes con LPO y 1.615 pacientes de la población general fueron recolectados usando un método estandarizado de registro. Los pacientes con LPO que estaban usando levotiroxina (LPO/levotiroxina+) fueron reexaminados para recolectar información sobre la existencia de lesiones de LPO y confirmar el diagnóstico de la enfermedad de la tiroides. Las características clínicas del LPO en este grupo fueron comparadas con un grupo, emparejado para edad y sexo, de pacientes con LPO sin historia de enfermedad de la tiroides o uso de levotiroxina (LPO/levotiroxina-). RESULTADOS: Aproximadamente el 11% (n = 170) de los pacientes con LPO estaban medicados con levotiroxina comparado con el 2.5% (n = 40) de los controles (OR multivariado 2.99, 95% CI 2.03-4.44; P < .0001). No se encontraron diferencias entre el perfil de la enfermedad de la tiroides entre los grupos. En el momento de la reexaminación, los pacientes con LPO/levotiroxina- mostraron más lesiones eritematosas de LPO y se quejaron de síntomas más severos en comparación con el grupo LPO/levotiroxina+ (P < .001). CONCLUSIÓN: La prevalencia de la enfermedad de la tiroides en pacientes con LPO es significativamente mayor que en la población general. Las lesiones de LPO en pacientes con enfermedad de la tiroides concomitante tiene una presentación diferente a través del tiempo, lo cual indica un subgrupo específico de LPO."

Conventional agricultural practices are often contrary to human health and environmental conservation. Use of and exposure to pesticides in agricultural communities in tropical countries is a pressing public health problem and an important facet of environmental degradation. This research project was undertaken by documenting use and exposure behaviors among agricultural communities in San Cristobal, Antioquia (Colombia). The research questions were: (1) What are the primary factors associated with the use of pesticides and do those factors differ between pesticide users and agroecological adherents? (2) How do campesino pesticide users and agroecological adherents(non-pesticide users) differ in their attitudes and beliefs with regards to pesticide use and exposure? and (3) How do these factors influence campesinos‟ behaviors associated with pesticide use and exposure? I implemented qualitative and quantitative methods in this investigation. The qualitative approach was based on community participatory ethnographic research. The latter involved participant observation, interviews, and focus groups aimed at existing pesticides users and agroecological adherents. The quantitative approach used questionnaires to derive demographic information, scale-based evaluations of attitudes and beliefs, pesticides decision making, perceived confidence, and perceived control. Findings showed that the most relevant factors related to pesticide use and their categories included: a) individual: beliefs, attitudes and knowledge; b) interpersonal: family support and cultural acceptance of pesticide use; c) economic: fear of living within financially unviable constraints, market conditions and lack of economic support from the government; d) cultural: collective acceptance or tolerance of pesticide use and exposure and onset of negative reactions when stopping pesticide use; e) political: deficient regulations for controlling pesticide use control and adequate utilization of protective equipment. Pesticide users experienced the most apprehension regarding stopping pesticide use as they often believed pesticides allow them to obtain better crop yields and, therefore, higher monetary gains. Pesticide users lacked a positive attitude toward personal protectionequipment, regardless of the risks to which they may be exposed. Pesticide training was deficient in this population showing a clear need to improve safety conditions and training to reduce occupational hazards. Future studies should explore with greater detail these attitudes and beliefs so as to promote mid- to long-term public health interventions that directly address the sense of food and income insecurity found among the population of pesticides users, which blocks their transition into a non-pesticide scenario for agricultural production. Over the short-term, public health programs should continue to educate the population of pesticide users on the immediate risks of exposure. The decision making process surrounding pesticide use in the studied population was influenced by a variety of factors. Campesinos who were prone to use pesticides for their crops often exhibited diminished degrees of knowledge about adverse effects of pesticides on human health, believed pesticides are necessary for their crops, had negative attitudes about stopping pesticide use, had a strong family influence toward the use of pesticides, experienced economic fear of stopping pesticide use, cultivated flowers as their main source of income, expressed strong social acceptance of pesticide use, experienced negative community reactions when attempting to stop pesticide use, received government subsidies for pesticide use, and had never received any training on the use of required protective equipment. Campesinos who showed more proclivities towards the use of pesticides were convinced that pesticides are necessary for their crops as they guarantee substantial yields and larger specimens of the different crop varieties. They also exhibited low perceived control, low perceived confidence, and a low perception of adverse pesticide effects on human health and the natural environment. Future studies are required to fully comprehend the unique occupational health and safety needs of these campesinos. Additionally, future studies should be aimed at designing and introducing long-term, well-structured public health interventions to increase awareness about the harmfulness of pesticides on human and environmental health so as to promote a well-established behavioral change in relation to pesticides use reduction among these communities.

Tesis de Nicolás Osorio para optar al título de Doctor en Medicina, en la Facultad de Medicina de París, en 1865. A lo largo del documento, escrito en francés, Osorio analiza el comportamiento de los tumores que obstruyen el líquido cefalorraquídeo.

Abstract: Dengue is a widely spread vector-borne disease. Dengue cases in the Americas have increased over the last few decades, affecting various urban spaces throughout these continents, including the tourism-oriented city of Girardot, Colombia. Interactions among mosquitoes, pathogens and humans have recently been examined using different temporal and spatial scales in attempts to determine the roles that social and ecological systems play in dengue transmission. The current work characterizes the spatial and temporal behaviours of dengue in Girardot and discusses the potential territorial dynamics related to the distribution of this disease. Methods: Based on officially reported dengue cases (2012–2015) corresponding to epidemic (2013) and inter-epidemic years (2012, 2014, 2015), space (Getis-Ord index) and space-time (Kulldorff’s scan statistics) analyses were performed. Results: Geocoded dengue cases (n = 2027) were slightly overrepresented by men (52.1%). As expected, the cases were concentrated in the 0- to 15-year-old age group according to the actual trends of Colombia. The incidence rates of dengue during the rainy and dry seasons as well as those for individual years (2012, 2013 and 2014) were significant using the global Getis-Ord index. Local clusters shifted across seasons and years; nevertheless, the incidence rates clustered towards the southwest region of the city under different residential conditions. Space-time clusters shifted from the northeast to the southwest of the city (2012–2014). These clusters represented only 4.25% of the total cases over the same period (n = 1623). A general trend was observed, in which dengue cases increased during the dry seasons, especially between December and February. Conclusions: Despite study limitations related to official dengue records and available fine-scale demographic information, the spatial analysis results were promising from a geography of health perspective. Dengue did not show linear association with poverty or with vulnerable peripheral spaces in intra-urban settings, supporting the idea that the pathogenic complex of dengue is driven by different factors. A coordinated collaboration of epidemiological, public health and social science expertise is needed to assess the effect of “place” from a relational perspective in which geography has an important role to play. Resumen: El dengue es una enfermedad trasmitida por vectores ampliamente distribuida. En las últimas décadas el dengue ha aumentado en América, afectando diferentes espacios urbanos del continente incluyendo la ciudad turística de Girardot, Colombia. La interacción entre mosquitos, patógenos y humanos se ha examinado usando diferentes escalas espaciales y temporales para determinar la función que tienen los sistemas sociales y ecológicos en la transmisión del dengue. Este trabajo caracteriza el comportamiento espacial y temporal del dengue en Girardot y discute el potencial que tienen las dinámicas territoriales en la distribución de esta enfermedad. Métodos: Se realizaron análisis espaciales (Índice Getis-Ord) y espaciotemporales (Estadística de Kulldorff) utilizando los reportes oficiales de casos de dengue (2012-2015), los cuales corresponden a periodos epidémicos (2013) e interepidémicos (2012, 2014, 2015). Resultados: Dentro de los casos georreferenciados (n = 2027) hubo una representación ligeramente mayor de hombres (52.1%). Según lo esperado, de acuerdo a las tendencias actuales en Colombia, los casos se concentraron en la población de 0 a 15 años. El índice de Getis-Ord fue significativo para las tasas de incidencia de dengue en periodo de lluvia y periodo de sequía, al igual que para los años de estudio (2012, 2013 and 2014). Se identificaron conglomerados locales en toda la ciudad, sin embargo, estos se agruparon en la parte suroeste de la ciudad en diferentes condiciones residenciales. Los conglomerados espaciotemporales se desplazaron del noreste hacia el suroeste de la ciudad (2012–2014). Estos conglomerados espaciotemporales representan solo el 4.25% del total de casos del periodo (n = 1623). Se identificó una tendencia general de aumento de casos durante la época de sequía, especialmente entre diciembre y febrero. Conclusiones: A pesar de las limitaciones relacionadas a los registros oficiales de casos de dengue y la información demográfica disponible, los resultados fueron promisorios desde la perspectiva de la geografía de la salud. El dengue no mostró una relación lineal con la pobreza o con espacios periféricos vulnerables en espacios intraurbanos. Esto apoya la idea que el complejo patogénico del dengue comprende múltiples factores. Se requiere de una colaboración coordinada entre la epidemiología, la salud pública y las ciencias sociales para evaluar el efecto que tiene el “lugar” desde una perspectiva relacional donde la geografía tiene un rol importante a desempeñar.

Many low- and middle-income countries are experiencing a rapid increase of overweight and obesity rates. Nonetheless, there are some concerns not only about the pace of the increase in overweight and obesity, but also about inequalities in their distribution across social groups. The main aims of this thesis were to: i) examine socioeconomic differences in overweight and obesity over the last decades among women of childbearing age in low- and middle- income countries; ii) determine the contribution of reproductive variables (e.g., parity, age at first birth, breastfeeding) to socioeconomic inequalities in overweight and obesity in low- and middle-income countries; and iii) assess the impact of recently adopted poverty reduction policies, namely conditional cash transfer programs (CCT) on determinants of child health and children´s nutritional status. Overall, the prevalence of overweight and obesity among women has increased in most low- and middle-income countries across all educational groups and occupational classes in the last two decade. Nonetheless, overweight and obesity trends have rapidly increased among less educated and lower occupational classes especially in North Africa/West and Central Asia (NWA), Sub-Saharan (SS) and Latin America and the Caribbean (LAC) region. For example, women working in agriculture and production sector had an annual increase in the prevalence of overweight/obesity ranged from 2.8% in LAC region to 3.7% in the SS region. In addition, women with lower age at first birth, high parity, and shorter duration of breastfeeding had an increased odds of overweight. Nonetheless, those reproductive factors did not play a key role in explaining differences in overweight by socioeconomic status and related trends. Finally, the CCT Familias en Accion was associated with significant higher BMI z-scores among children beneficiaries of this program; BMI-for-age z-scores (β=0.14, 95%CI 0.00, 0.27, p <0.05). These results suggest that in future years, the unequal distribution of body weight between and within societies likely contributes to perpetuate poverty and poor health as in high-income countries. In addition, poverty reduction policies such as CCT programs in a middle- income country such as Colombia have not been very successful in preventing overweight and obesity. Therefore, additional efforts specifically focused on preventing an increase in inequalities in overweight and obesity are needed, targeting mothers and children from low income households.

Abstract: Bone remodeling is a continuous physiological process that requires constant generation of new osteoblasts from mesenchymal stem cells (MSCs). Differentiation of MSCs to osteoblast requires a metabolic switch from glycolysis to increased mitochondrial respiration to ensure the sufficient energy supply to complete this process. As a consequence of this increased mitochondrial metabolism, the levels of endogenous reactive oxygen species (ROS) rise. In the current study we analyzed the role of forkhead box O3 (FOXO3) in the control of ROS levels in human MSCs (hMSCs) during osteogenic differentiation. Treatment of hMSCs with H2O2 induced FOXO3 phosphorylation at Ser294 and nuclear translocation. This ROS-mediated activation of FOXO3 was dependent on mitogen-activated protein kinase 8 (MAPK8/JNK) activity. Upon FOXO3 downregulation, osteoblastic differentiation was impaired and hMSCs lost their ability to control elevated ROS levels. Our results also demonstrate that in response to elevated ROS levels, FOXO3 induces autophagy in hMSCs. In line with this, impairment of autophagy by autophagy-related 7 (ATG7) knockdown resulted in a reduced capacity of hMSCs to regulate elevated ROS levels, together with a reduced osteoblast differentiation. Taken together our findings are consistent with a model where in hMSCs, FOXO3 is required to induce autophagy and thereby reduce elevated ROS levels resulting from the increased mitochondrial respiration during osteoblast differentiation. These new molecular insights provide an important contribution to our better understanding of bone physiology. Resumen: La remodelación ósea es un proceso fisiológico continuo que demanda la generación constante de nuevos osteoblastos a partir de células madre mesenquimales (CMMs). La diferenciación de las CMMs a osteoblastos requiere un cambio de glicólisis a respiración mitocondrial para así asegurar la obtención de suficiente energía. Como consecuencia, los niveles endógenos de especies reactivas del oxígeno (ERO) se elevan siendo perjudiciales para la integridad celular. En el presente estudio hemos analizado el papel de FOXO3 en el control de ERO en las CMMs durante la diferenciación osteogénica. El tratamiento de las CMMs con H2O2 induce la fosforilacion de FOXO3 en la serina 294 resultando en la translocación de FOXO3 al núcleo. Dicha activación mediada por el aumento de ERO es dependiente de la actividad de JNK. Al disminuir los niveles de FOXO3, la diferenciación osteoblástica se deteriora y las CMMs pierden su capacidad para controlar los niveles de ERO. Adicionalmente, nuestros resultados demuestran que en presencia de ERO, FOXO3 induce la autofagia en CMMs. En este orden de ideas, la disminución en los niveles de ATG7 da lugar a una reducción de la capacidad de las CMMs para regular los niveles elevados de ERO, junto con una reducción de la diferenciación de osteoblastos. Tomados en conjunto, nuestros resultados son consistentes con un modelo en el que FOXO3 es necesario para inducir la autofagia y por lo tanto reducir los niveles elevados de ERO que resultan del aumento de la respiración mitocondrial durante la diferenciación de osteoblastos. Estos nuevos conocimientos moleculares son importantes para una mejor comprensión de la fisiología ósea.

Transcriptional activity of Forkhead box transcription factor class O (FOXO) proteins can result in a variety of cellular outcomes depending on cell type and activating stimulus. These transcription factors are negatively regulated by the phosphoinositol 3-kinase (PI3K)–protein kinase B (PKB) signaling pathway, which is thought to have a pivotal role in regulating survival of tumor cells in a variety of cancers. Recently, it has become clear that FOXO proteins can promote resistance to anti-cancer therapeutics, designed to inhibit PI3K–PKB activity, by inducing the expression of proteins that provide feedback at different levels of this pathway. We questioned whether such a feedback mechanism may also exist directly at the level of FOXO-induced transcription. To identify critical modulators of FOXO transcriptional output, we performed gene expression analyses after conditional activation of key components of the PI3K–PKB–FOXO signaling pathway and identified FOXP1 as a direct FOXO transcriptional target. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that FOXP1 binds enhancers that are pre-occupied by FOXO3. By sequencing the transcriptomes of cells in which FOXO is specifically activated in the absence of FOXP1, we demonstrate that FOXP1 can modulate the expression of a specific subset of FOXO target genes, including inhibiting expression of the pro-apoptotic gene BIK. FOXO activation in FOXP1-knockdown cells resulted in increased cell death, demonstrating that FOXP1 prevents FOXO-induced apoptosis. We therefore propose that FOXP1 represents an important modulator of FOXO-induced transcription, promoting cellular survival.

This report compiles the results of a research project aimed at describing the current palliative care situation in eight Latin American countries. The project’s general objective—to raise awareness and influence public policy around the need to approach palliative care from a human rights perspective—was achieved through rapprochement among professionals from various fields in the region, which in and of itself is a key step forward in terms of bringing together communities that defend patients’ rights with communities that advocate a drug policy embracing a public health focus. We hope that this diagnostic report is useful for professional associations, health professionals, patients’ rights advocates, drug policy reform activists, and decision makers, who can rely on its findings to better integrate palliative care into general health services and to use human rights language to promote public policy reform and guarantee the human rights of those in the Americas who suffer from severe and chronic pain. Description tooked from: https://www.dejusticia.org/publication/palliative-care-a-human-rights-approach-to-health-care-2/ Consulte la versión en español en la siguiente URL: http://babel.banrepcultural.org/cdm/ref/collection/p17054coll31/id/30

Mowinga es un proyecto de impacto social que busca desarrollar una compañía dedicada a la producción y comercialización de productos 100% orgánicos a base de una planta llamada Moringa cuyas hojas y rama contienen múltiples nutrientes y propiedades alimenticias que le permiten a sus consumidores tener una alimentación balanceada. Este proyecto busca ser implementado en la región Caribe en donde se ve la problemática con la nutrición de los niños de bajo recursos y Mowinga puede significar la solución de raíz a ese impacto social que buscará darle solución a la poca y mala alimentación de dichos niños. También se busca llegar a las nuevas tendencias a nivel mundial sobre la "onda fit" en donde nuestros potenciales clientes buscarán con nuestros productos mejorar su estilo de vida y lograr ser saludables. Nuestro producto será Polvo de Hojas de Moringa Orgánico 100% puro, ideal para ser consumido en ensaladas, infusiones, sopas o con diferentes tipos de bebidas, para todo el público que busca beneficios. generales de salud y bienestar y será comercializado en las siguientes presentaciones: Caja moringa en polvo x 20 sachets x 200 gr Tarro de 90 cápsulas de moringa x 50 gr Sobre sellado moringa en polvo 200 gr