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The main purpose of this paper is to develop a systematic, spatially explicit approach to the analysis of the ecosystem services provided by the metropolitan landscape that can act as a support for green infrastructure planning. To achieve this, we have proposed a set of indicators to assess and map nine ecosystem services—including regulating, provisioning, habitat and cultural services. This methodology has been applied to three case studies in the south of Spain: the metropolitan areas of Seville, Malaga-Marbella and Cordoba. Despite the geographical proximity of these areas to one another, the indicators show that there are significant differences in their potentialities and available resources to form a multipurpose green space system. The results suggest that further reflection is needed on how the concept of green infrastructure can be applied to metropolitan areas, especially in the Mediterranean region and other similar geographical contexts. Instead of understanding green infrastructure strictly in terms of a network of interconnected green spaces and natural areas, planning initiatives should assign a more important role to the landscape matrix and, in particular, to the multifunctional cultivated space on the urban fringe. In addition, more thought needs to be given to how to create functional green corridors in the metropolitan landscape for public use and habitat conservation. From the perspective of spatial planning, the methodology proposed has been demonstrated to be a useful tool to identify key spaces for the provision of ecosystem services.

The growing processes of the socio-economic inequality resulting from the neoliberal political model are evident in large Spanish cities, with a spatial dimension that allows us to visualise its contradictions with great clarity. These social contradictions are particularly marked among the most vulnerable and foreign population groups. For this reason, the study of the spaces and services termed Social Infrastructures (SI), as facilities which favour social integration and cohesion in the city, is of special importance. Our study addresses the distribution of SI in the Spanish cities of Madrid and Barcelona, their relationship with the level of vulnerability in the neighbourhoods and the distribution of the Spanish and foreign population in a novel way, by creating a synthetic SI index and using a non-hierarchical clustering method. Our results show two completely different city models: in Barcelona, SI are distributed following the criterion of socio-territorial equity, while in Madrid, there is a greater presence of SI in the wealthier areas. This leads us to reflect on the social and political implications of our results in both cities.

Screening programs for colorectal cancer (CRC) are standard in most developed countries because they reduce mortality and are cost-effective. Within them, colonoscopy allows to directly visualize the colon and remove neoplastic lesions. However, it is an expensive exam with low adherence in asymptomatic individuals. The fecal occult blood test (FOBT) is a low-cost and risk-free method for the user, which results in a high rate of adherence, explaining its use in most screening programs. This article analyzes the effectiveness of different fecal occult blood tests in screening programs. The main conclusions are that the sensitivity of the guaiac-based chemical test for the detection of colorectal cancer is lower than that observed with qualitative and quantitative immunological tests. Automated quantitative methods allow objective readings independent of the operator and the reaction reading time, necessary for the analysis of large numbers of samples. The participation rate with immunological FOBTs is higher than with chemical ones, which is why they are preferred by the different countries that have screening programs. The use of quantitative tests allows stratification of symptomatic and asymptomatic patients at higher risk, in the screening programs.

Resumen: El análisis de los cambios en la localización residencial de la población migrante resulta fundamental a la hora de entender el proceso de segregación residencial que experimentan a nivel metropolitano. Incluso, según el modelo de asimilación espacial, la elección de vecindario puede considerarse un indicador de su grado de integración en la sociedad de acogida. Partiendo del análisis espacial de dichos cambios residenciales en dos áreas metropolitanas de Andalucía, Málaga y Almería durante el periodo 2003-2013, el presente artículo analiza los distintos modelos de incorporación residencial a la sociedad de acogida y la influencia del componente socioterritorial. Los resultados obtenidos muestran la inserción como modelo de incorporación a la ciudad predominante. Inserción que al ser meramente residencial suele derivar en la estigmatización socio-territorial de los barrios donde se concentra el inmigrante lo que dificulta su adecuada integración y plena incorporación a la sociedad de acogida. Abstract: The analysis of the residential changes of the migrant population is essential at the time of understand the process of residential segregation at the metropolitan level. Even, according to spatial assimilation model, the choice of neighborhood it can be considered an indicator of the degree of integration into the host society. Starting from a spatial analysis of residential changes of inmigrant on two metropolitan areas of Andalusia, Málaga y Almería over the period 2003-2013, this paper analyzes the different models of residential incorporation to the host society and the influence of socio-territorial component. The results show the prevalence of insertion as a model for incorporation into the city. Insertion to the being merely residential often leads to territorial stigmatization of neighborhoods where it concentrates the inmigrant making it difficult their proper integration and full integration into the host society.

Background: General anesthesia is a safe, frequent procedure in clinical practice. Although it is very unusual in procedures not related to head and or neck surgery, vocal cord paralysis is a serious and important complication. Incidence has been associated with patient age and comorbidities, as well as the position of the endotracheal tube and cuff. It can become a dangerous scenario because it predisposes aspiration. Objectives: To present a case and analyze the risk factors associated with increased risk of vocal cord paralysis described in the literature. Case report: 53 year-old diabetic man, who developed hoarseness in the postoperative period after receiving general anesthesia for an elective abdominal laparoscopic surgery. Otolaryngological evaluation showed left vocal cord paralysis. Conclusions: Vocal cord paralysis can be a serious complication of general anesthesia because of important voice dysfunction and risk of aspiration. The management is not yet fully established, so prevention and early diagnosis is essential. Resumo: Justificativa: A anestesia geral é um procedimento seguro e frequente na prática clínica. Embora seja muito rara em procedimentos não relacionados à cirurgia de cabeça ou pescoço, a paralisia das cordas vocais é uma complicação séria e importante. Sua incidência tem sido associada à idade e comorbidades do paciente, bem como à posição do tubo endotraqueal e seu balonete. A paralisia das cordas vocais pode ser uma condição perigosa porque predispõe à aspiração. Objetivos: Apresentar um caso e analisar os fatores de risco associados ao aumento do risco de paralisia das cordas vocais descritos na literatura. Relato de caso: Paciente do sexo masculino, 53 anos, diabético, que desenvolveu rouquidão no pós-operatório após anestesia geral para cirurgia laparoscópica abdominal eletiva. A avaliação otorrinolaringológica mostrou paralisia da corda vocal esquerda. Conclusões: A paralisia de cordas vocais pode ser uma complicação séria da anestesia geral devido ao risco grave de disfunção da voz e aspiração. O manejo dessa condição ainda não está totalmente estabelecido, de modo que a prevenção e o diagnóstico precoce são essenciais. Keywords: Vocal cord paralysis, Intubation, General anesthesia, Hoarseness, Palavras-chave: Paralisia de cordas vocais, Intubação, Anestesia geral, Rouquidão

Colorectal cancer (CRC) is one of the most common cancers worldwide. As with other cancers, CRC is a multifactorial disease due to the combined effect of genetic and environmental factors. Most cases are sporadic, but a small proportion is hereditary, estimated at around 5-10%. In both, the tumor interacts with heterogeneous cell populations, such as endothelial, stromal, and immune cells, secreting different signals (cytokines, chemokines or growth factors) to generate a favorable tumor microenvironment for cancer cell invasion and metastasis. There is ample evidence that inflammatory processes have a role in carcinogenesis and tumor progression in CCR. Different profiles of cell activation of the tumor microenvironment can promote pro or anti-tumor pathways; hence they are studied as a key target for the control of cancer progression. Additionally, the intestinal mucosa is in close contact with a microorganism community, including bacteria, bacteriophages, viruses, archaea, and fungi composing the gut microbiota. Aberrant composition of this microbiota, together with alteration in the diet‐derived microbial metabolites content (such as butyrate and polyamines) and environmental compounds has been related to CRC. Some bacteria, such as pks+ Escherichia coli or Fusobacterium nucleatum, are involved in colorectal carcinogenesis through different pathomechanisms including the induction of genetic mutations in epithelial cells and modulation of tumor microenvironment. Epithelial and immune cells from intestinal mucosa have Pattern-recognition receptors and G-protein coupled receptors (receptor of butyrate), suggesting that their activation can be regulated by intestinal microbiota and metabolites. In this review, we discuss how dynamics in the gut microbiota, their metabolites, and tumor microenvironment interplays in sporadic and hereditary CRC, modulating tumor progression.

La noción de infraestructura verde se ha consolidado en los últimos años como una potente herramienta conceptual y metodológica para la mejora ambiental en ámbitos urbanos y metropolitanos. Dos de sus principios esenciales son, de un lado, la interconexión física y funcional de los espacios verdes y zonas naturales presentes en el territorio, y de otro, el fomento de los servicios ecosistémicos en el entorno urbano y periurbano. Ambos objetivos suponen una nueva perspectiva para la planificación de las grandes aglomeraciones urbanas, e invitan a repensar nuestra forma de entender y ordenar el espacio libre metropolitano. El presente trabajo se propone aportar elementos de reflexión sobre esta cuestión, tomando como base el análisis de la provisión de servicios ecosistémicos y la cartografía de la multifuncionalidad ambiental en el área metropolitana de Sevilla. El cálculo de un conjunto de indicadores para servicios de regulación, provisión, culturales y vinculados a la preservación de la biodiversidad, junto con la estimación de un índice sintético de multifuncionalidad para el espacio libre, permitirán valorar las potencialidades y limitaciones que ofrece el concepto de infraestructura verde para su aplicación a escala metropolitana. La noció d'infraestructura verda s'ha consolidat en els últims anys com una potent eina conceptual i metodològica per a la millora ambiental en àmbits urbans i metropolitans. Dos dels seus principis essencials són, d'una banda, la interconnexió física i funcional dels espais verds i zones naturals presents en el territori, i de l'altra, el foment dels serveis ecosistèmics en l'entorn urbà i periurbà. Tots dos objectius suposen una nova perspectiva per a la planificació de les grans aglomeracions urbanes, i inviten a repensar la nostra manera d'entendre i ordenar l'espai lliure metropolità. El present treball es proposa aportar elements de reflexió sobre aquesta qüestió, prenent com a base l'anàlisi de la provisió dels serveis ecosistèmics i la cartografia de la multi-funcionalitat ambiental a l'àrea metropolitana de Sevilla. El càlcul d'un conjunt d'indicadors per als serveis de regulació, provisió, culturals i vinculats a la preservació de la biodiversitat, juntament amb l'estimació d'un índex sintètic de multi-funcionalitat per a l'espai lliure, permetran valorar les potencialitats i limitacions que ofereix el concepte de infraestructura verda per a la seva aplicació a escala metropolitana. The notion of green infrastructure has been consolidated in recent years as a powerful conceptual and methodological tool for environmental improvement in urban and metropolitan areas. Two of its basic principles are, on the one hand, the physical and functional interconnection of green spaces and natural areas present in the territory, and on the other, the promotion of ecosystem services in the urban and peri-urban environment. Both objectives represent a new perspective for the planning of large urban agglomerations and invite us to rethink our way of understanding and planning the metropolitan open space. This paper aims to provide some elements for reflection on this subject, based on the analysis of the provision of ecosystem services and the mapping of environmental multifunctionality in the Seville metropolitan area. The calculation of a set of indicators for regulation, provision, cultural and nature conservation-related services, together with the estimation of a synthetic multifunctionality index for the metropolitan open space, will allow us to assess the potential and limitations of the green infrastructure concept regarding its application at a metropolitan scale. Los autores agradecen la financiación recibida para el desarrollo de esta investigación por parte del Ministerio de Ciencia, Innovación y Universidad, a través del Programa Estatal de I+D+i (proyecto RTI2018-095325-B-I0). Asimismo, agradecen a los dos revisores anónimos del manuscrito sus comentarios y observaciones, que han contribuido a mejorar significativamente el presente trabajo.

Screening programs for colorectal cancer (CRC) are standard in most developed countries because they reduce mortality and are cost-effective. Within them, colonoscopy allows to directly visualize the colon and remove neoplastic lesions. However, it is an expensive exam with low adherence in asymptomatic individuals. The fecal occult blood test (FOBT) is a low-cost and risk-free method for the user, which results in a high rate of adherence, explaining its use in most screening programs. This article analyzes the effectiveness of different fecal occult blood tests in screening programs. The main conclusions are that the sensitivity of the guaiac-based chemical test for the detection of colorectal cancer is lower than that observed with qualitative and quantitative immunological tests. Automated quantitative methods allow objective readings independent of the operator and the reaction reading time, necessary for the analysis of large numbers of samples. The participation rate with immunological FOBTs is higher than with chemical ones, which is why they are preferred by the different countries that have screening programs. The use of quantitative tests allows stratification of symptomatic and asymptomatic patients at higher risk, in the screening programs.

Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher’s exact and/or chi-square test. Survival curves were estimated with Kaplan–Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.

Este artículo analiza la diferente incidencia que muestra la erosión estimada de suelos en las áreas de influencia socioeconómica de los Parques Nacionales de Doñana y Sierra Nevada en el marco de los procesos de Naturbanización. La Naturbanización se define por la capacidad de atracción de población y actividades económicas hacia las áreas de influencia socioeconómica de espacios protegidos debida al reconocimiento de sus valores ambientales y paisajísticos. Se establece la metodología de procesado de datos con un Sistema de Información Geográfica para llevar a cabo el estudio diacrónico de los valores estimados de erosión que proporciona la Junta de Andalucía para toda la Comunidad Autónoma. Aplicando dicha metodología a las cuencas del arroyo de El Partido y del río Trevélez se pretende contribuir a una mejor comprensión de las relaciones de causalidad o de potenciación existentes entre los factores climáticos, las actividades humanas y los procesos erosivos. Se ha llevado a cabo un análisis estadístico de las cartografías raster publicadas de estimación de erosión media mensual y de las variables empleadas para su cálculo entre 2003 y 2014. Se ha constatado la relevancia que los usos y coberturas vegetales tienen como variable clave para explicar la distribución de los valores medios de erosión en ambas cuencas. En la cuenca del río Trevélez la evolución de las tasas de erosión estimada ha mostrado un mayor paralelismo con la erosividad de la lluvia, mientras que en el arroyo de El Partido han sido los cambios de usos del suelo los que determinan en mayor medida dicha evolución.

IntroducciA³n: el objetivo de este estudio fue establecer una asociaciA³n entre diversas variables demogrAificas y epidemiolA³gicas con la agresividad del cAincer de prA³stata (CaP).MA©todos: pacientes diagnosticados con CaP respondieron una encuesta que incluye el nivel de educaciA³n, los factores de riesgo cardiovascular (FRCV), los antecedentes familiares (HF) de CaP, consumo de alcohol, tabaquismo y otros. Se utilizA³ anAilisis univariado y multivariado (AMV) para establecer si los factores mencionados anteriormente afectan las variables asociadas con la agresividad del CaP, como la edad al momento del diagnA³stico, el A­ndice de Gleason, los mAirgenes positivos (MP) y la metAistasis A³seas (MO), entre otras.Resultados: se incluyeron ciento setenta y dos hombres en el anAilisis. Los pacientes con HF fueron diagnosticados a edades mAis tempranas que los pacientes sin HF (55,73 vs 66,45 aA±os, p = 0,0001). Los pacientes que beben tienen un mayor nAomero de MP que los pacientes que no (15 vs 4 pacientes, p = 0,04). El AMV mostrA³ que los pacientes que consumen alcohol y los que fuman (activos o suspendidos) tuvieron un mayor riesgo de MP (OR = 4,45 y 4,1, IC 95% 1,16-17,07 y 1,14-14,72, respectivamente, ambos p

Over the past decade, it has become increasingly important to develop and utilize specific methods for modeling fisheries with limited data. The sustainable development of aquatic resources and fisheries management requires an understanding of species exploitation despite limited knowledge or poor data. Many data-limited assessment methods are based on catch data and assumptions, with little consideration given the biological aspects of the species under study. Herein, a population depletion model is reparametrized to simplify biological reference point estimates related to a maximum sustainable yield. This model includes biological aspects (parameter probability distributions), the fishery history, and levels of population depletion as perceived by the fishers. This approach was used with landings data (2000–2014) for Lessonia berteroana, a brown kelp harvested off north-central Chile (25°17′S–29°30′S). Management of this kelp is in its early stages, with no formal procedures established for assessment. We estimated population variables and reference points for three zones and considered beached seaweed to represent biomass mortality due to natural causes. The results, which accounted for uncertainty in resilience (steepness of the stock-recruitment relationship), natural mortality, process error, and minimum proportions of beached kelp, contributed to our understanding of this fishery and allowed us to propose an assessment tool for fisheries with poor or limited data.

Se aislaron 82 cepas bacterianas a partir de muestras de sedimento del Caribe colombiano, capaces de tolerar los contaminantes orgánicos persistentes en ambientes aeróbicos. De estas cepas, 64 sobrevivieron las condiciones de laboratorio, 43 se aislaron a partir de medios de cultivos enriquecidos con plaguicidas organoclorados (DDT y Aldrin) y 21 de medios enriquecidos con hidrocarburos (Crudo y ACPM). Las cepas fueron sometidas a un proceso de selección con el fin de escoger bacterias competitivas para constituir cultivos mixtos y evaluar su capacidad de degradación de hidrocarburos (ACPM) y plaguicidas organoclorados (DDT). Los resultados obtenidos muestran que el cultivo mixto crecido en presencia de hidrocarburos (CMH) fue capaz de degradar el 68,61% de la fracción de los n-alcanos del ACPM en 21 días. El cultivo bacteriano desarrollado en presencia de plaguicidas organoclorados (CMO), transformó un 68,8% de DDT a DDD en 60 días. Un 23,54% de la degradación de hidrocarburos alifáticos y un 29,1% de DDT, fue debido a factores abióticos. Las cepas se identificaron mediante la amplificación del gen 16s rRNA, encontrando en el CMO bacterias de los géneros Acinetobacter, Brevibacillus y Pseudomonas, y en el CMH microorganismos correspondientes a los géneros Bacillus, Enterobacteriaceae, Klebsiella, Pseudomonas y Ralstonia. Las cepas evaluadas presentan potencial en la degradación de COP y a futuro pueden ser empleadas como una herramienta estratégica de biorremediación.

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

Background: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. Aim: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways. Material and Methods: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. Results: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases. Conclusions: This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.

Si bien la expansión urbana es un proceso normal relacionado con el crecimiento de la población y de sus actividades, se considera como incontrolado cuando el crecimiento urbano es más rápido que el crecimiento demográfico (European Environment Agency -JCR 2006-2011). Sabemos que los orígenes de este descontrol se encuentran en un cambio en la manera de habitar el territorio y conllevan un mayor consumo de recursos. La falta de consideración sistémica de este consumo de suelo en la planificación del desarrollo territorial sigue siendo un problema importante al cual se enfrenta la sociedad española a pesar de la crisis económica que azota el país. En este sentido, el artículo pretende aportar algunos elementos conceptuales e instrumentales que ofrezcan la posibilidad de analizar en perspectiva el proceso de creación y consolidación territorial y demográfico de las áreas metropolitanas andaluzas. Con ello se busca valorar la cohesión territorial del crecimiento en base a principios básicos de sostenibilidad social y ambiental, tal como lo plantea la futura agenda urbana europea. Los resultados apuntan a un comportamiento bastante sostenible de las áreas metropolitanas andaluzas a pesar del profundo cambio en el modelo de desarrollo metropolitano.

PURPOSE Little is known about the genetic predisposition to breast and ovarian cancer among the Chilean population, in particular genetic predisposition beyond BRCA1 and BRCA2 mutations. In the current study, we aim to describe the germline variants detected in individuals who were referred to a hereditary cancer program in Santiago, Chile. METHODS Data were retrospectively collected from the registry of the High-Risk Breast and Ovarian Cancer Program at Clínica Las Condes, Santiago, Chile. Data captured included index case diagnosis, ancestry, family history, and genetic test results. RESULTS Three hundred fifteen individuals underwent genetic testing during the study period. The frequency of germline pathogenic and likely pathogenic variants in a breast or ovarian cancer predisposition gene was 20.3%. Of those patients who underwent testing with a panel of both high- and moderate-penetrance genes, 10.5% were found to have pathogenic or likely pathogenic variants in non- BRCA1/2 genes. CONCLUSION Testing for non- BRCA1 and -2 mutations may be clinically relevant for individuals who are suspected to have a hereditary breast or ovarian cancer syndrome in Chile. Comprehensive genetic testing of individuals who are at high risk is necessary to further characterize the genetic susceptibility to cancer in Chile.

Developing high levels of competence in the execution of surgical procedures through training is a key factor for obtaining good clinical results in healthcare. To improve the effectiveness of the training, it is advisable to provide feedback to each student tailored to how the student has performed the procedure on each occasion. Current state-of-the-art feedback is based on Checklists and Global Rating Scales, which indicate whether all process steps have been carried out and the quality of each execution step. However, there is a process perspective that is not captured successfully by these instruments, e.g., steps performed, but in an undesired order, group of activities that are repeated an unnecessary number of times, or an excessive transition time between two consecutive steps. In this research, we propose a novel use of process mining techniques to effectively identify desired and undesired process patterns regarding rework, the order in which activities are performed, and time performance, in order to complement the tailored feedback for surgical procedures using a process perspective. The proposed approach was applied to analyze a real case of ultrasound-guided Central Venous Catheter placement training. It was quantitatively and qualitatively validated that the students who participated in the training program perceived the process-oriented feedback they received as favorable for their learning.

Background: General anesthesia is a safe, frequent procedure in clinical practice. Although it is very unusual in procedures not related to head and or neck surgery, vocal cord paralysis is a serious and important complication. Incidence has been associated with patient age and comorbidities, as well as the position of the endotracheal tube and cuff. It can become a dangerous scenario because it predisposes aspiration. Objectives: To present a case and analyze the risk factors associated with increased risk of vocal cord paralysis described in the literature. Case report: 53 year-old diabetic man, who developed hoarseness in the postoperative period after receiving general anesthesia for an elective abdominal laparoscopic surgery. Otolaryngological evaluation showed left vocal cord paralysis. Conclusions: Vocal cord paralysis can be a serious complication of general anesthesia because of important voice dysfunction and risk of aspiration. The management is not yet fully established, so prevention and early diagnosis is essential.

It was assessed the parasitic relationship between by 2 morphospecies of microphallid metacercariae and their second intermediate host, the amphipod Apohyale hirtipalma with the body length and sex of the hosts, and the abundance of shore birds (definitive hosts). Amphipod mortality induced by the parasites was assessed through the relationship between the variance/mean parasite abundance ratio with host body length for each metacercariae morphospecies. Four sites at the Biobío Region (36°S), Chile, were selected because of contrasting abundance of potential definitive hosts (Aves: Laridae), from where 240 amphipods were collected from intertidal pools (60 in each sampling locality). Total prevalence was 57.5% and metacercariae found, belonged to 2 unidentified morphospecies of microphallid subfamilies (Microphallinae, 28.3% and Maritrematinae, 36.7%). The prevalence and abundance of metacercariae increased with the amphipod body, although their variations were associated to the abundance of shorebirds. The prevalence of Microphallinae did not have differences among sexes in their relationship with the host body length, while among Maritrematinae, male amphipods showed higher prevalence than females of similar body length. It was also determined that Maritrematinae would cause more mortality than Microphallinae. Local variations of the abundance of other hosts involved in the microphallid life cycles as well as of prevailing local environmental conditions and amphipod behavior may be keys for a better understanding of the abundance and prevalence variations of these parasites.

Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p &lt, 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.

L’article propose une méthode détaillée pour délimiter les aires métropolitaines espagnoles à partir de la variable mobilité « domicile-travail ». Cette méthodologie est fondée sur une trajectoire longue et consolidée au regard des expériences internationales comparées. Elle est appliquée ici aux données du recensement de 2011. La contribution de l’article porte sur deux questions : tout d’abord l’explication et la discussion en détail de toutes les étapes et décisions prises dans le processus de délimitation puis une comparaison entre les résultats obtenus et ceux produits par la délimitation de l’OCDE et de l’INE-Urban Audit. Les conclusions démontrent à la fois la robustesse du processus méthodologique adopté pour la délimitation des espaces métropolitains mais aussi la nécessité d’ajouter des données de nature morphologique afin de considérer les nouvelles formes et organisations des espaces métropolitains contemporains. This paper presents a detailed methodological proposal for the definition of Spanish metropolitan areas. The methodology is based upon a key variable, commuting, which is highly used internationally, and it is applied to 2011 census data. The contribution of the article deals with two questions : firstly, the explanation and detailed discussion of all the steps and decisions taken in the delimitation process, and secondly, a comparison between the results obtained and those produced by the delimitation of the OECD and the INE-Urban Audit. The conclusions demonstrate both the robustness of the methodological process adopted for delimiting metropolitan areas and the need to add morphological data in order to consider the new forms and organization of contemporary metropolitan areas. Este artículo presenta una propuesta metodológica detallada para la delimitación de las áreas metropolitanas españolas. La metodología está basada en la utilización de la variable movilidad residencia-trabajo, que en la experiencia comparada internacional es la que tiene una trayectoria más amplia y contrastada, y que aquí se aplica a los datos del censo de 2011. La aportación del artículo se centra en dos cuestiones. En primer lugar, la explicación y discusión en detalle de todos los pasos y decisiones que se han tomado en el proceso de delimitación. En segundo lugar, la realización de un ejercicio de comparación de los resultados con propuestas de delimitación alternativas, las de la OCDE y la del INE-Urban Audit. Las conclusiones muestran a la vez la robustez del proceso metodológico elegido para la delimitación de los espacios metropolitanos pero también la necesidad de ir incluyendo variables y dimensiones de naturaleza morfológica en dicho proceso para adecuarla a las nuevas formas y organización de los espacios metropolitanos contemporáneos. 本文具体提出定义西班牙都市圈的一种方法。该方法论建立在通勤状况这一关键的变量上。通勤状况被国际学术界广泛采用作为界定都市圈的切入点，这一方法也适用于2011年西班牙的普查数据。本文的主要贡献在于解决了两个问题：首先，本文解释了界定都市圈过程当中的所有步骤和所做的选择；其次，本文比较了由该方法得出的结论和由OECD和INE-Urban Audit所做出的界定。结论证明了本文所提出的定义方法具有稳健性，另外本文也指出该方法仍需纳入形态学数据从而能够补充完善当代都市圈的新的型态和组织方式。

Background: In Chile, a national colorectal cancer (CRC) screening program using immunochemical fecal occult blood tests and colonoscopy was started in 2012 as an international collaboration between Chile and Japan. In the present study, we quantified exosomes in the peripheral blood and evaluated the implication of the results for CRC screening. Methods: A total of 25 peripheral plasma samples from the participants of CRC screening in Punta Arenas, Chile, were analyzed for exosomes. Results: Plasma exosomes were obtained from 5 participants with adenocarcinoma (4 pTis and 1 pT1), 8 with high-grade adenoma, 4 with low-grade adenoma, 4 with hyperplastic polyps, and 4 with normal findings. Participants with adenocarcinoma had significantly higher amounts of plasma exosomes (2.1–3.2 fold) than participants with normal findings, hyperplastic polyps, or low-grade adenoma (p = 0.016, p = 0.0034, and p = 0.0042 respectively; Tukey’s multiple comparisons test). The size of the representative lesion, the number of lesions, and the sum of those 2 factors in each participant correlated significantly with the exosome amounts (r = 0.56, r = 0.58, and r = 0.72, respectively; p < 0.01; Spearman’s correlation coefficient test). Conclusions: This pilot study demonstrated that quantification of plasma exosomes is a potential alternative screening method for detecting individuals with a high risk of colorectal malignancy.

Background: In Chile, colorectal cancer (CRC) is often diagnosed in late stages. Thus, surgical treatment must be complemented with chemotherapy. KRAS mutations and microsatellite instability have been detected in these tumors. However, the response to treatment in patients without KRAS mutations varies and requires a better understanding. Aim: To determine the frequency and distribution of somatic point mutations in KRAS, BRAF and PIK3CA genes and microsatellite instability status (MSI) in patients with colon cancer (CC). Material and Methods: A prospective observational study of patients undergoing surgery for colon cancer. Tumor-derived DNA was analyzed by polymerase chain reaction (PCR) for the most frequent mutations of KRAS, BRAF and PIK3CA. PCR was also used to analyze MSI. Results: Fifty-eight patients with sporadic CC were analyzed, 16 showed KRAS mutations (G12R, G12D, G12V, G13D) and out of the 42 patients that did not show any mutation, 10 had mutations in BRAF (V600E) and PIK3CA (E542K, E545D, E545K, Q546E, H1047R). BRAF mutations alone or in combination with PIK3CA mutations were observed in 27% of high MSI tumors and in 2% of tumors without instability (p < 0.049). A higher percentage of high MSI tumors were located in the right colon (p < 0.001), and showed BRAF mutation (p < 0.020). Conclusions: The highest percentage of high MSI and BRAF mutations was observed in the right colon. Therefore, this study suggests the presence of different molecular features between right and left colon tumors that should be considered when defining the therapeutic management.

Background: The molecular testing of KRAS mutation status in metastatic colorectal cancer patients is mandatory to identify patients eligible for anti- epidermal growth factor receptor monoclonal antibody therapy. Aim: To report the frequency of KRAS gene mutations in Chilean patients with colorectal cancer (CRC). Material and Methods: A cohort of 262 Chilean patients with CRC aged 26 to 90 years (53% males), was studied. KRAS mutation status was analyzed by real-time polymerase chain reaction and correlated with clinicopathological data. Results: Ninety-eight patients (37%) were positive for KRAS mutations. G12D was the most common mutation with a frequency of 36.7%, followed by G12V (25.5%), G13D (17.3%), G12A (7.1%), G12C (6.1%), G12S (5.1%) and G12R (2%). The frequency of the mutation in left, right colon and rectal tumors was 37.8, 32.6 and 44.9%, respectively. Among tumors with mutations, 86.7% were well or moderately differentiated tumors and the rest were poorly differentiated. No significant associations between KRAS gene mutations and other clinicopathological features of the tumor were observed. Conclusions: The frequencies of KRAS mutations reported in this study are similar to frequencies reported for European and North-American populations, lower than in a Spanish study and higher than in a Peruvian study. (Rev Med Chile 2014; 142: 1407-1414)

ResumenDado el creciente número de pacientes con dispositivos electrónicos cardíacos implantables (DECI), que incluyen marcapasos y/o cardiovertores-desfibriladores implantables, el manejo perioperatorio de aquellos que serán sometidos a cirugía requiere que el equipo quirúrgico esté familiarizado con estos dispositivos y sus implicancias, con la finalidad de disminuir los eventos adversos. Las guías clínicas actuales recomiendan un manejo multidisciplinario. Sin embargo, cuando estas condiciones no son posibles, tanto el equipo quirúrgico como anestésico deben ser capaces de proveer un manejo perioperatorio seguro y efectivo. Este debe ser individualizado a cada paciente, tipo de dispositivo y procedimiento quirúrgico al que será sometido, por lo que una única recomendación no es apropiada para todos los casos. En esta revisión se describen las principales recomendaciones para el manejo perioperatorio de pacientes usuarios de marcapasos y/o cardiovertores-desfibriladores implantables.AbstractWith the increased number of patients with cardiac implantable electronic devices (CIED), which include pacemakers and/or implantable cardioverter- defibrillators, the perioperative management of those patients who will be undergoing surgery requires that surgical team to become familiar with these devices and their implications, in order to reduce the adverse outcomes. Current guidelines recommend a multidisciplinary approach of these patients. However, when these conditions are not feasible, both surgical and anesthesia team should be able to provide a safe and effective perioperative environment. This management should be individualized for each patient, type of device and surgical procedure; therefore a single recommendation is not appropriate for all cases. The main recommendations for the perioperative management of patients with pacemakers and/or implantable cardioverter-defibrillators are described in this review.

Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor.To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways.Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal.CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases.This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

Background: Selection of patients with Lynch Syndrome (LS) for a genetic study involves the application of clinical criteria. To increase the rate of identification of mutations, the use of molecular studies as Microsatellite Instability (MSI) and Im- munohistochemistry (IHC) in the tumor has been proposed. Aim: To demonstrate the usefulness of MSI and IHC in the detection of mutations in patients with LS. Material and Methods : From our Familial Colorectal Cancer Registry, families suspected of LS were selected according to Amsterdam or Bethesda clinical criteria. Screening of germline mutations of MLH1, MSH2 and MSH6 genes was performed. In addition, analysis of MSI and IHC were performed in colorectal tumors. Results : A total of 35 families were studied (19 met Amsterdam and 16 met Bethesda criteria). Twenty one families harbored a germline alteration in MLH1, MSH2 or MSH6 (18 Amsterdam and 3 Bethesda). In these families, eighteen different alterations were found, 15 of which were mutations and 3 corresponded to variants of uncertain pathogenicity. On the other hand, 80% of the tumors showed positive microsatellite instability (27 MSI-high and 1 MSI-low), and immunohistochemical testing showed that 77% of tumors had the loss of a protein. Correlation between results of tumor molecular studies and the finding of germline nucleotide change showed that IHC and MSI predicted mutations in 81 and 100% of patients, respectively. Conclusions : MSI and IHC can efficiently select patients with a high probability of carrying a mutation in DNA repair genes

Efforts have been made to develop a chemoprevention that selectively triggers apoptosis in malignant cancer cells. Here, we demonstrated that a mutated Ha-Ras activity is required in Anisomycin-induced apoptosis in transformed keratinocytes. Anisomycin stimulates JNK activity and apoptosis in oncogenic Ha-Ras positive cells, but not in normal keratinocytes. This effect was demonstrated in stably transfected cells with dominant negative Ha-Ras, that protected transformed cells, and oncogenic Ha-Ras that sensitized non-transformed cells to Anisomycin-induced apoptosis. Lastly, the treatment of cells with inhibitors of the JNK displayed resistance to Anisomycin induced apoptosis. These data suggests that the oncogenic Ha-Ras is important for Anisomycin-induced JNK activation and apoptosis in transformed keratinocytes.

In Chile, colorectal cancer (CRC) is often diagnosed in late stages. Thus, surgical treatment must be complemented with chemotherapy. KRAS mutations and microsatellite instability have been detected in these tumors. However, the response to treatment in patients without KRAS mutations varies and requires a better understanding.To determine the frequency and distribution of somatic point mutations in KRAS, BRAF and PIK3CA genes and microsatellite instability status (MSI) in patients with colon cancer (CC).A prospective observational study of patients undergoing surgery for colon cancer. Tumor-derived DNA was analyzed by polymerase chain reaction (PCR) for the most frequent mutations of KRAS, BRAF and PIK3CA. PCR was also used to analyze MSI.Fifty-eight patients with sporadic CC were analyzed, 16 showed KRAS mutations (G12R, G12D, G12V, G13D) and out of the 42 patients that did not show any mutation, 10 had mutations in BRAF (V600E) and PIK3CA (E542K, E545D, E545K, Q546E, H1047R). BRAF mutations alone or in combination with PIK3CA mutations were observed in 27% of high MSI tumors and in 2% of tumors without instability (p0.049). A higher percentage of high MSI tumors were located in the right colon (p0.001), and showed BRAF mutation (p0.020).The highest percentage of high MSI and BRAF mutations was observed in the right colon. Therefore, this study suggests the presence of different molecular features between right and left colon tumors that should be considered when defining the therapeutic management.

The molecular testing of KRAS mutation status in metastatic colorectal cancer patients is mandatory to identify patients eligible for anti-epidermal growth factor receptor monoclonal antibody therapy.To report the frequency of KRAS gene mutations in Chilean patients with colorectal cancer (CRC).A cohort of 262 Chilean patients with CRC aged 26 to 90 years (53% males), was studied. KRAS mutation status was analyzed by real-time polymerase chain reaction and correlated with clinicopathological data.Ninety-eight patients (37%) were positive for KRAS mutations. G12D was the most common mutation with a frequency of 36.7%, followed by G12V (25.5%), G13D (17.3%), G12A (7.1%), G12C (6.1%), G12S (5.1%) and G12R (2%). The frequency of the mutation in left, right colon and rectal tumors was 37.8, 32.6 and 44.9%, respectively. Among tumors with mutations, 86.7% were well or moderately differentiated tumors and the rest were poorly differentiated. No significant associations between KRAS gene mutations and other clinicopathological features of the tumor were observed.The frequencies of KRAS mutations reported in this study are similar to frequencies reported for European and North-American populations, lower than in a Spanish study and higher than in a Peruvian study.

To study the association between the polymorphisms Arg462Gln and Asp541Glu from the RNASEL gene (1q25), and the polymorphisms rs620861, rs1447295, rs6983267, rs7837328 from the chromosome 8q24 with the risk of presenting prostate cancer (PCa) and its clinical characteristics in a Hispanic (Chilean) population. The study was performed on 21 control patients and 83 patients diagnosed with PCa. Polymorphisms were analysed from blood samples through real-time PCR by using TaqMan probes, and the genetic analysis was performed with the SNPStats program. Also, a comparison was performed between clinical characteristics of PCa and the presence of the different polymorphism genotypes by using the Minitab software. There was a significant association between the genotype G/G from the polymorphism rs6983267 with an overall increased risk of PCa, in patients both with or without family history of PCa (OR = 4.47, 95% CI = 1.05–18.94, P = 0.034 and OR = 3.57, 95% CI = 0.96–13.35, P = 0.037, respectively). Regarding clinical parameters, patients carrying the genotype C/C from the polymorphism Asp541Glu had significantly higher prostate-specific antigen (PSA) levels than patients carrying the other genotypes (P = 0.034). Moreover, patients with the genotype G/G of rs6983267 had higher PSA levels (P = 0.024). The polymorphism rs6983267 from region 3 of the chromosome 8q24 appears to be a prominent risk factor for PCa and a biomarker for cancer aggressiveness in the group of patients who presented higher levels of PSA at the time of diagnosis.