Gli1 mediates lung cancer cell proliferation and sonic hedgehog-dependent mesenchymal cell activation.

Non-Small-Cell-Lung-Cancer (NSCLC) represents approximately 85% of all lung cancers and remains poorly understood. While signaling pathways operative during organ development, including Sonic Hedgehog (Shh) and associated Gli transcription factors (Gli1-3), have recently been found to be reactivated in NSCLC, their functional role remains unclear. Here, we hypothesized that Shh/Gli1-3 could mediate NSCLC autonomous proliferation and epithelial/stromal signaling in the tumoral tissue. In this context, we have investigated the activity of Shh/Gli1-3 signaling in NSCLC in both, cancer and stromal cells. We report here that inhibition of Shh signaling induces a significant decrease in the proliferation of NSCLC cells. This effect is mediated by Gli1 and Gli2, but not Gli3, through regulation of cyclin D1 and cyclin D2 expression. While exogenous Shh was unable to induce signaling in either A549 lung adenocarcinoma or H520 lung squamous carcinoma cells, both cells were found to secrete Shh ligand, which induced fibroblast proliferation, survival, migration, invasion, and collagen synthesis. Furthermore, Shh secreted by NSCLC mediates the production of proangiogenic and metastatic factors in lung fibroblasts. Our results thus provide evidence that Shh plays an important role in mediating epithelial/mesenchymal crosstalk in NSCLC. While autonomous Gli activity controls NSCLC proliferation, increased Shh expression by NSCLC is associated with fibroblast activation in tumor-associated stroma. Our study highlights the relevance of studying stromal-associated cells in the context of NSCLC regarding new prognosis and therapeutic options

Modelo de co-creación en mypimes: estudio de caso en el sector lácteo de Bogotá, Colombia

Micro and small companies in Colombia need to strengthen their competitive, sustainable and sustainable advantages to respond, adapt and sustain themselves in the market; they must concentrate their efforts on knowledge management, ICT innovation, continuousimprovement, and co-Creation. This document presents a co-creation model based on knowledge management that allows innovating in the dairy sector, as a form of adaptation and survival, of differentiation and competitiveness as well as a tool for decision-making. The methodology adopted to solve the problem posed and to check the research hypothesis combines situations and predominant attitudes that propose solutions and evaluation alternatives for the development of strategies that allow generating competitive advantages and continuously improving the processes of Msmes in the dairy sector, and that, as a consequence, decrease the socioeconomic difficulties that afflict these Msmes. For the analysis of the competitiveness models of Msmes in the dairy sector in Bogota, the methodology adopted by the research group “Electronic Commerce in Colombia”(Gicoecol), was used to contextualize the competitiveness problem of Msmes in the dairy sector, as well as aspects of learning processes, creation and/or personalization of products and/or services offered, and applications of this type of model in other sectors or in large companies. Based on the information collected through the analysis stage, the study structured a model based on knowledge management and value co-creation, in order to be a base tool to improve competitiveness, generate strategies at an internal and external level, standardize and formalize their processes and increase their profitability; fundamental variables were identified for the construction of the model; Finally, the proposal was validated by measuring the acceptance of the proposed model.Las micro y pequeñas empresas en Colombia requieren fortalecer sus ventajas competitivas, sostenibles y sustentables para responder, adaptarse y sostenerse en el mercado; deben concentrar sus esfuerzos en la gestión del conocimiento, la innovación las TIC, el mejoramiento continuo, y la co-creación. Este documento presenta un modelo de co-creación basado en la gestión del conocimiento que permita innovar en el sector lácteo como forma de adaptación y supervivencia, así como de diferenciación y competitividad como herramientas para la toma de decisiones. La metodología adoptada para resolver el problema planteado y comprobar la hipótesis de investigación combina situaciones y actitudes predominantes que proponen soluciones y alternativas de evaluación para el desarrollo de estrategias que permitan generar ventajas competitivas y mejorar continuamente los procesos de las mipymes (micro, pequeñas y medianas empresas) del sector lácteo y que como consecuencia disminuyan las dificultades socioeconómicas que aquejan a estas mipymes. Para el análisis de los modelos de competitividad de las mipymes del sector lácteo en Bogotá, se utilizó la metodología adoptada por grupo de investigación “Comercio electrónico en Colombia” (Gicoecol), se contextualiza la problemática de competitividad de las mipymes del sector lácteo, así como aspectos de procesos de aprendizaje, creación y/o personalización de productos y/o servicios ofrecidos, y aplicaciones de este tipo de modelos en otros sectores o en grandes empresas. Con base en la información recolectada a través de la etapa de análisis, se estructura un modelo basado en la gestión del conocimiento y co-creación de valor con el fin de ser una herramienta base para mejorar la competitividad, de que se generen estrategias en los niveles interno y externo y se estandaricen y formalicen sus procesos e incrementen su rentabilidad, se identificaron variables fundamentales para la construcción del modelo; por último, se realizó la validación de la propuesta mediante la medición de la aceptación del modelo propuesto

Alteraciones Neuropsicológicas y Emocionales en Niños Prematuros de muy Bajo Peso al Nacer

 La  prematuridad  es  uno  de  los  problemas  de  salud  más  prevalentes  en  la población infantil de los países desarrollados. Entre un 8 y un 10% de los nacimientos ocurren antes de la 37ª semana de gestación y justifican el 75 % de la mortalidad perinatal y el 50% de la discapacidad en la infancia. El principal objetivo de este trabajo fue realizar una evaluación de las posibles secuelas  neuropsicológicas  y  emocionales  a  los  7  años  de  edad  de  niños prematuros  comparándolo  con  niños  de  la  misma  edad  pero  nacidos  a término.  Instrumentos: Historias  Clínicas  y  Entrevistas.  Batería  de Evaluación Neuropsicológica Infantil (BENI). Sistema de Evaluación de la Conducta  de  niños  y  Adolescentes  (BASC).  Los  resultados  han  mostrado que los niños prematuros presentan alteraciones centradas en la memoria la  función  ejecutiva  en  la  evaluación  neuropsicológica  y  en  problemas  de conducta  y  de  atención  en  la  evaluación  psicopatológica.  Estos  resultados deberían  considerarse  para  iniciar  programas  de  intervención  en  los  dos ámbitos  descritos  que  ayuden  a  estos  niños  a  superar  las  dificultades  que manifiestan por la presencia de dichos problemas. Palabras claves: Prematuridad;  Niños;  Secuelas  neuropsicológicas  y  emocionales;  Batería Neuropsicológica (BENI).   Memory Consolidation and Neural Substrate of Reward: Prematurity is one of the most relevant health problems among children in the developed countries.  Around  8  to  10%  of  children  birth  before  the  37  week  and/or with  a  very  low  birth  weight  (VLBW)  (1500  g).  This  causes  75%  of  the prenatal  mortality  and  the  50%  of  the  children  disability.  The  aim  of  this study  was  to  assess  neuropsychological  and  emotional  impairments  in  7 year old children who were born VLBW. A clinical interview, the Children Neuropsychological  Assessment  Battery,  and  the  Behavioral  Assessment System for Children (BASC) were administrated. VLBW children showed memory  and  executive  function  deficits,  as  well  as,  behavioral  and attention  problems.  These  results  highlight  the  importance  of  long  term follow up of the VLBW children and point out the necessity of developing adequate  neuropsychological  and  emotional  treatment  program  for  these children. Key Words: Prematurity; very low birth weight children; neuropsychological and emotional consequences; Bateria de Evaluación Neuropsicologica Infantil (BENI).

Observación de la Responsabilidad Social Empresarial de las Actividades Económicas de Cafam para Sufragar la Crisis Sanitaria en Colombia

Anexo 1. Enlace del Código de Ética https://docs.google.com/document/d/1bQLyK3lauwtoJckS-DTxsouM2q6r3vtrsF5BVLCAOYQ/edit?usp=sharing Anexo 2. Formato de Recolección de Información https://forms.gle/ipULqmCjv6C6pMyM6Cafam es una empresa prestadora de servicios con una alta trayectoria en el mercado, contando con un gran posicionamiento de marca, el cual la convierte en objeto de estudio para la presente investigación. La responsabilidad social se crea a raíz de preocupación del deterioro severo del medio ambiente, por tal motivo todo tipo de organización que tenga en sus objetivos corporativos como énfasis responsabilidad social en su entorno, marca la diferencia ya que hace que sus empresas puedan contribuir con el mejoramiento continuo de las condiciones laborales y ambientales en el mercado. Por esto es importante identificar que programas tiene en la actualidad Cafam, que tengan como objetivo implementar la responsabilidad social, y así conocer de primera mano (de sus colaboradores) como desde su rol contribuyen a la consecución satisfactoria del programas ambientales, sociales, laborales, comerciales y corporativos. De igual manera con la recolección de información obtenida mediante la encuesta, se logra evidenciar que se presentan algunas falencias en el uso de los recursos naturales y la contaminación del entorno en el campo de recreación, por tal motivo como equipo de trabajo, se organiza un plan de estudio que ayude a minimizar el desperdicio de los recursos naturales y el daño ambiental por sus actividades, los cuales van hacer eje fundamental de estudio con el fin de lograr una solución parcial o definitiva a la problemática que presenta.Cafam is a service provider company with a long history in the market, with a great brand positioning, which makes it the object of study for this research. Social responsibility is created as a result of the reintegration of social resources obtained by companies, for this reason any type of organization that has in its corporate objectives as an emphasis social responsibility in its environment makes a difference since it makes its companies can contribute with the continuous improvement of labor and environmental conditions in the market. For this reason, it is important to identify what programs Cafam currently has, which have the objective of implementing social responsibility, and thus learn first-hand (from its collaborators) how, from their role, they contribute to the satisfactory achievement of environmental, social, labor, commercial and corporate. In the same way with the collection of information obtained through the survey, it is possible to show that there are some shortcomings in the use of natural resources and the contamination of the environment in the recreation field, for this reason as a work team, a study plan that helps minimize the waste of natural resources and environmental damage due to its activities, which will be the fundamental axis of study in order to achieve a partial or definitive solution to the problem it presents

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers’ feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.Part of the research currently in progress in the authors' laboratory is funded by the company Hero Spain, S. A. through the grant #3582 managed by the Fundacion General Empresa-Universidad de Granada

Landscape - wildfire interactions in southern Europe: implications for landscape management

ReviewEvery year approximately half a million hectares of land are burned by wildfires in southern Europe, causing large ecological and socio-economic impacts. Climate and land use changes in the last decades have increased fire risk and danger. In this paper we review the available scientific knowledge on the relationships between landscape and wildfires in the Mediterranean region, with a focus on its application for defining landscape management guidelines and policies that could be adopted in order to promote landscapes with lower fire hazard. The main findings are that (1) socio-economic drivers have favoured land cover changes contributing to increasing fire hazard in the last decades, (2) large wildfires are becoming more frequent, (3) increased fire frequency is promoting homogeneous landscapes covered by fire-prone shrublands; (4) landscape planning to reduce fuel loads may be successful only if fire weather conditions are not extreme. The challenges to address these problems and the policy and landscape management responses that should be adopted are discussed, along with major knowledge gapsinfo:eu-repo/semantics/publishedVersio

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years