Protocol description and initial experience in kidney graft perfusion using infrared thermography.

PURPOSE: Protocol description for renal perfusion study using thermographic technology and description of the thermographic and clinical behavior of the transplanted kidneys before and after unclamping. METHODS: Infrared thermographic images of renal grafts are obtained before kidney reperfusion, 10 min after and just before closing the surgical wound. Thermographic data is evaluated together with the type of graft and donor, cold ischemia time, hypovascularized areas determined by the surgeon during surgical intervention, alterations in vascular flow in postoperative echo-Doppler, time at the beginning of graft function and serum creatinine monitoring during postoperative follow-up. RESULTS: 17 grafts were studied. The mean temperature of the grafts before reperfusion, 10 min after and at the end of the surgery were 18.7 °C (SD 6.27), 32.36 °C (SD1.47) and 32.07 °C (SD1.78) respectively. 4 grafts presented hypoperfused areas after reperfusion. These areas presented a lower temperature compared to the well perfused parenchyma surface using thermographic images. CONCLUSION: The study of the usefulness and applicability of thermography can allow the development of tools that provide additional objective information on organ perfusion in real time and non-invasive manner. Our protocol and initial results can contribute to provide new evidence. Further analyses should be developed to shed light on the role of this technology.

WeBirth Study: Diseño del Cuestionario para Evaluar la Experiencia del Parto en Agua (CEEPA) en la población española / WeBirth Study: design of the Questionnaire for Assessing the Waterbirth Experience (CEEPA) in the Spanish population

El objetivo general de este trabajo es diseñar un cuestionario para evaluar la experiencia del parto en agua, denominado Cuestionario para Evaluar la Experiencia del Parto en Agua (CEEPA). Consta de dos fases: la primera es la creación del cuestionario y la segunda, la obtención de las propiedades psicométricas. Metodología: El diseño del cuestionario consta de 3 pasos. En primer lugar, tres matronas expertas independientes realizaron una revisión bibliográfica y definieron los ítems del cuestionario, creando un cuestionario de 25 ítems. En segundo lugar, un grupo de expertos evaluó la validez del contenido según la suficiencia, claridad, coherencia y relevancia de los ítems, obteniendo un cuestionario de 15 ítems que tiene una concordancia «aceptable» superior a 0.70 en el coeficiente de concordancia de Kendall (W) . Finalmente, un grupo de mujeres gestantes evaluó la comprensibilidad del cuestionario analizando su claridad, tiempo de cumplimentación, comprensión, relevancia y aceptabilidad, y otro grupo de 6 mujeres puérperas valoró los ítems mediante una entrevista cognitiva. Resultados: Durante el proceso de diseño se ha reducido el número de ítems de 25 a 17, los cuales evalúan la experiencia del parto en las dimensiones de ambiente/entorno, proceso del parto, estado emocional y recién nacido. El 90 % de las participantes consideraron que los ítems eran concretos y precisos, con un adecuado tiempo de cumplimentación y un formato correcto. obteniendo un cuestionario de 15 ítems que tiene una concordancia «aceptable» superior a 0,70 en el coeficiente de concordancia de Kendall (W) Conclusiones: La versión final del CEEPA consta de 17 ítems que evalúan 5 dimensiones relacionadas con el parto en agua. Está pendiente de una segunda fase, donde se obtendrán las propiedades psicométricas para su validación. (AU)

The general objective of this study is to design a questionnaire to evaluate the waterbirth experience called Questionnaire for Assessing the Waterbirth Experience (CEEPA in Spanish). It is divided into two phases, the first part consisted of creating the questionnaire and the second of obtaining its psychometric properties.Methodology: The questionnaire design consists of 3 steps. First, three independent expert midwives conducted a literature review and defined the questionnaire items, creating a 25-item questionnaire. Secondly, a group of experts carried out the content validity evaluation about sufficiency, clarity, coherence, and relevance, obtaining a 15-item with an «acceptable» concordance of more than 0.70 in Kendall's coefficient of concordance (W). Finally, a pregnant women group evaluated the questionnaire’s comprehensibility by analyzing its clarity, completion time, understanding, relevance, and acceptability, and another group with 6 postpartum women evaluated the questionnaire items throughout a cognitive interview.Results: During the questionnaire design process, the number of questionnaire items has been reduced from 25 to 17, which evaluates the experience of childbirth in the dimensions of environment, the birth process, emotional state, and newborn. 90% of the participants considered the items concrete and precise, with adequate completion time and a correct format.Conclusions: The final version of the CEEPA consists of 17 items that evaluate 5 dimensions related to waterbirth. A second phase is pending to obtain the psychometric properties for its validation. (AU)

Evidence that Xylella fastidiosa is the Causal Agent of Almond Leaf Scorch Disease in Alicante, Mainland Spain (Iberian Peninsula).

In 2017, Xylella fastidiosa, a quarantine plant-pathogenic bacterium in Europe, was detected in almond trees associated with leaf scorch symptoms in Alicante, a Mediterranean area in southeastern mainland Spain. The bacterium was detected by serological and molecular techniques, isolated in axenic culture from diseased almond trees, and identified as X. fastidiosa subsp. multiplex sequence type (ST) 6. Inoculation experiments on almond plants in greenhouse trials with a characterized strain of X. fastidiosa subsp. multiplex ST6 isolated in the outbreak area have proved that it was able to multiply and systemically colonize inoculated plants. Disease symptoms characteristic of leaf scorch like those observed in the field were observed in the inoculated almond trees after 1 year. Furthermore, the pathogen was reisolated and identified by molecular tests. With the fulfillment of Koch's postulates, we have demonstrated that X. fastidiosa is the causal agent of the almond leaf scorch disease in the Alicante outbreak.

Resultados oncológicos de un programa de prostatectomía radical asistida por robot «da Vinci» en una cohorte de 408 pacientes consecutivos / Oncologic outcomes in 408 consecutive patient cohort treated with da Vinci robot-assisted radical prostatectomy

El objetivo de este estudio es evaluar las características generales y los resultados oncológicos en una cohorte de 408 casos de prostatectomía radical asistida por robot da Vinci Standard de 4 brazos, realizadas entre octubre del 2006 y febrero del 2015. El análisis estadístico se realizó con el programa SPSS 20.0. Las variables cualitativas se presentan con su distribución de frecuencias y las cuantitativas con su media y desviación estándar o mediana y rango intercuartil. La asociación entre variables cualitativas se analizó con el test de la χ2. La variable de resultado de la supervivencia libre de enfermedad se evaluó con un análisis de curvas de Kaplan-Meier y se contrastaron las diferencias con el test de Breslow. Se ajustó un modelo de regresión de Cox. Entre los resultados destacamos un seguimiento 47 meses (32-68,75 meses), supervivencia libre de recurrencia 90 meses (IC del 95%, 86-94), mediana de tiempo a recurrencia de 23 meses (10,5-37 meses), recurrencia del 16,6% (68/408), recidiva bioquímica (62/498, 15,2%) y un 22% de complicaciones, la mayoría Clavien I-II. Los resultados se resumen en las tablas 1 a 7 y en la figura 1. CONCLUSIONES: 1) la prostatectomía radical robótica es una técnica segura con un porcentaje asumible de complicaciones, en su mayoría menores (grados I y II de Clavien); 2) encontramos mayor probabilidad de permanecer libre de recidiva en los grados más bajos de la clasificación de ISUP y mayor probabilidad de recidiva en casos de alto riesgo, y 3) en el modelo multivariante comprobamos que el grado ISUP se relacionó de forma significativa con la supervivencia y fueron variables pronosticas independientes los grados de la clasificación ISUP y los márgenes quirúrgicos positivos

The objective of this study is to evaluate the general characteristics and oncological results in a cohort of 408 cases submitted to da Vinci Standard 4-armed robot-assisted radical prostatectomy (RARP), performed between October 2006 and February 2015 at Clínico San Carlos hospital. Statistical analysis was performed with the SPSS 20.0 program. Qualitative variables are presented with their frequency distribution and quantitative variables with their mean and standard deviation or median and interquartile range. The χ2 test was used to analyze the association of qualitative variables. The disease-free survival outcome variable was evaluated with a Kaplan-Meier curve analysis, and the differences were contrasted with the Breslow test. A Cox regression model was adjusted. Among the results, we highlight the follow-up of 47 months (32-68.75 m), recurrence-free survival of 90 months (95% CI, 86-94), median time to recurrence of 23 months (10.5-37 m), recurrence 16'6% (68/408), biochemical recurrence (62/498, 15'2 %) and 22% of complications, mostly Clavien I-II. The results are summarized in Tables 1 to 7 and Figure 1

Oncologic outcomes in 408 consecutive patient cohort treated with da Vinci robot-assisted radical prostatectomy. / Resultados oncológicos de un programa de prostatectomía radical asistida por robot «da Vinci¼ en una cohorte de 408 pacientes consecutivos.

The objective of this study is to evaluate the general characteristics and oncological results in a cohort of 408 cases submitted to da Vinci Standard 4-armed robot-assisted radical prostatectomy (RARP), performed between October 2006 and February 2015 at Clínico San Carlos hospital. Statistical analysis was performed with the SPSS 20.0 program. Qualitative variables are presented with their frequency distribution and quantitative variables with their mean and standard deviation or median and interquartile range. The χ2 test was used to analyze the association of qualitative variables. The disease-free survival outcome variable was evaluated with a Kaplan-Meier curve analysis, and the differences were contrasted with the Breslow test. A Cox regression model was adjusted. Among the results, we highlight the follow-up of 47 months (32-68.75m), recurrence-free survival of 90 months (95% CI, 86-94), median time to recurrence of 23 months (10.5-37 m), recurrence 16'6% (68/408), biochemical recurrence (62/498, 15'2%) and 22% of complications, mostly Clavien I-II. The results are summarized in Tables 1 to 7 and Figure 1. CONCLUSIONS: 1) RARP is a safe technique with an acceptable percentage of complications, mostly minor (Clavien grades iandii), 2) We found a higher probability of remaining recurrence-free in the lower grades of the ISUP classification and a higher probability of recurrence in high-risk cases, and 3) The multivariate model showed that the ISUP grade was significantly related to survival and the ISUP and PSM classification grades were independent prognostic variables.

Efficacy of Direct-acting Antivirals to Improve Clinical Condition, Fibrosis, and Liver Function in Liver Transplant Recipients Infected by Hepatitis C.

BACKGROUND: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C, including transplant recipients with an advanced fibrosis stage. Our aim in this study was to assess the clinical and functional benefits and improvement in liver fibrosis after treatment with DAAs in liver transplant recipients with chronic hepatitis C virus who achieved sustained virologic response (SVR). METHODS: We retrospectively analyzed 42 patients who underwent liver transplantation (LT) at our institution and were treated with DAAs from June 2014 to December 2015. Two patients died, so we ultimately included 40 transplant patients with chronic hepatitis C who received DAAs and achieved SVR. We assessed liver function, fibrosis stage, and clinical features at the start of the treatment, and then at 6 and 12 months after SVR. The indication for LT was hepatocellular carcinoma in 8 patients (20%) and Child-Pugh score B/C in 32 patients (80%). RESULTS: The DAAs regimens were sofosbuvir plus daclatasvir (45.0%), simeprevir plus sofosbuvir (42.5%), sofosbuvir plus ledipasvir (7.5%), and ombitasvir/paritaprevir/ritonavir (5%). The mean Modified End-stage Liver Disease (MELD) score pretreatment was 10.78, and was 8.46 at 1 year after treatment (P < .05). In addition, fibrosis stage decreased significantly from 14.81 kPa to 9.07 kPa (FibroScan) at 12 months after SVR. Clinically, there was a significant improvement, including control of ascites and chronic hepatic encephalopathy. CONCLUSION: DAAs were used successfully in the treatment of hepatitis C after orthotopic liver transplantation and resulted in significant improvement in liver function as measured by MELD score, fibrosis level, and cirrhotic clinical condition, even in patients with very advanced disease.

Combined application of Life Cycle Assessment and linear programming to evaluate food waste-to-food strategies: Seeking for answers in the nexus approach.

The great concern regarding food loss (FL) has been studied previously, but in an isolated way, disregarding interdependencies with other areas. This paper aims to go a step further by proposing a new procedure to assess different waste management alternatives based on the nexus approach by means of an integrated Water-Energy-Food-Climate Nexus Index (WEFCNI). The environmental profile of the waste management techniques is determined using Life Cycle Assessment (LCA) which, in combination with Linear Programming (LP), explores the optimal aggregation of weighting factors that lead to an aggregated nexus index. The management of residues from the anchovy canning industry in Cantabria (Spain) has been used as a case study, considering the three current applied alternatives: (i) valorisation of FL as animal feed in aquaculture (food waste-to-food approach), (ii) incineration of FL with energy recovery, and (iii) landfilling with biogas recovery. The last two considered the use of energy recovered to produce a new aquaculture product (food waste-to-energy-to-food scenarios). The results indicate that incineration is the best performing scenario when the nutritional energy provided by the valorisation alternative is not high enough and the valorisation technology presents the highest water consumption. Therefore, a minimisation in the consumption of natural resources is suggested in order to improve the application of circular economy within the sector. The use of the nexus index as an environmental management tool is extendable to any food system with the aim of facilitating the decision-making process in the development of more sustainable products.

Metabolic Syndrome After Liver Transplantation: Five-Year Prevalence and Risk Factors.

Survival after orthotopic liver transplantation (OLT) has increased over the last decades, focusing on the metabolic complications that contribute to patient morbidity and mortality. The aim of our study was to describe the prevalence of metabolic syndrome (MS), its components, and its associated factors in patients who underwent OLT in a hospital in Spain. From November 2001 to January 2014, we performed 415 transplantations in 386 patients. We analyzed 204 patients with a minimum follow-up of 1 year (77.6% were male and the mean age was 54.2+/-9.5 years). The most frequent etiology was alcohol (41%), followed by hepatitis C virus (29.1%). The indication was decompensated cirrhosis in 51.8% and hepatocellular carcinoma in 34%. According to modified National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATP III) criteria, 5 years post-transplantation MS was diagnosed in 38.2% of patients. Significant independent predictors of post-transplantation MS on logistic regression analysis were as follows: pretransplantation obesity (odds ratio [OR], 3.09; P = .056), 1-year post-transplantation obesity (OR, 3.95; P = .009), pretransplantation diabetes (OR, 4.63; P = .001), 1-year post-transplantation diabetes (OR, 3.01; P = .015), 1-year post-transplantation hypertension (OR, 1.85; P = .176), and hypertriglyceridemia at the first year after transplantation (OR, 2.32; P = .063). In our center the prevalence of MS at 5 years after OLT is slightly lower than published. The most important risk factors were obesity and diabetes (both pretransplantation and the first year post-transplantation).

Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues. This document summarizes the recommendations.

Coriocarcinoma postgestacional / Post-pregnancy choriocarcinoma

El coriocarcinoma es una patología infrecuente pero potencialmente fatal si no se trata. Se incluye dentro de las neoplasias trofoblásticas gestacionales, un grupo de tumores malignos altamente invasivos, metastáticos y muy vascularizados. Su presentación tras una gestación a término conlleva peor pronóstico que tras un aborto o una mola hidatiforme porque refleja un retraso en el diagnóstico y tratamiento. Describimos el caso de una paciente que acudió al servicio de urgencias, refiriendo metrorragia escasa desde un parto normal hace dos meses y posteriormente presentó un sangrado grave durante su hospitalización. Los elevados niveles de β-hCG, la ecografía-Doppler, las pruebas de imagen y las manifestaciones clínicas fueron suficientes para diagnosticar un coriocarcinoma postparto. El tratamiento precoz con poliquimioterápicos permitió una evolución favorable de la paciente.

Choriocarcinoma is an infrequent disease but potentially fatal if untreated. It is included in trophoblastic gestational neoplasia, a range of malignant tumors highly invasive, metastatic and very vascular. Its presentation after term pregnancies carries a worse prognosis than after a miscarriage or a hydatidiform mole because it reflects a delay in diagnosis and treatment. We report the case of a patient who presented to the emergency department referring little metrorrhagia from a normal delivery two months ago and severe bleeding later during her hospital stay. The high serum β-hCG level, the Doppler ultrasonography, the imaging test and the clinical manifestation were enough to diagnose a non-metastatic postpartum choriocarcinoma. Early treatment with polychemotherapy allowed a favorable evolution of the patient.

In vivo horizontal dissemination of the blaKPC-2 gene carried on diverse genetic platforms among clinical isolates of Enterobacteriaceae.

This study investigated the molecular characteristics of six blaKPC-positive Enterobacteriaceae recovered from three patients in Argentina. Antimicrobial susceptibility testing was performed following Clinical and Laboratory Standards Institute (CLSI) 2014 recommendations. Molecular characterisation of the isolates was performed by biparental conjugation, PCR, sequencing, S1 nuclease restriction, and Southern blot hybridisation with a blaKPC probe using standard protocols and conditions. The isolates studied were as follows. Case 1: Escherichia coli (ECO-P1) and Klebsiella pneumoniae (KPN-P1) isolated from a rectal swab harboured blaKPC-2 in transposon Tn4401a on non-typeable and non-conjugative plasmids. Case 2: Enterobacter cloacae (ECL-P2) and K. pneumoniae (KPN-P2) were isolated from two blood cultures. blaKPC-2 was found in a novel genetic variant of ISKpn8-blaKPC-2-ISKpn6-like on conjugative plasmids of IncL/M type. Case 3, Citrobacter freundii (CFR-P3) and Klebsiella oxytoca (KOX-P3) were isolated from skin and skin-structure infection. The blaKPC gene was detected on ISKpn8-ΔblaTEM-blaKPC-2-ISKpn6-like located on an IncA/C conjugative plasmid. CFR-P3 and KOX-P3 harboured blaPER-2 in addition to the blaKPC gene. In conclusion, we document the horizontal dissemination of blaKPC-2 from diverse Enterobacteriaceae clinical isolates with different genetic backgrounds. This is the first report of E. coli harbouring blaKPC associated with Tn4401a in Argentina.

Totally laparoscopic right-lobe hepatectomy for adult living donor liver transplantation: useful strategies to enhance safety.

The overriding concern in living donor liver transplantation is donor safety. A totally laparoscopic right hepatectomy without middle hepatic vein for adult living donor liver transplantation is presented. The surgical procedure is described in detail, focusing on relevant technical aspects to enhance donor safety, specifically the hanging maneuver and dynamic fluoroscopy-controlled bile duct division.

CD133+ cell content correlates with tumour growth in melanomas from skin with chronic sun-induced damage.

BACKGROUND: Melanoma is responsible for almost 80% of the deaths attributed to skin cancer. Stem cells, defined by CD133 expression, have been implicated in melanoma tumour growth, but their specific role is still uncertain. OBJECTIVES: We hypothesized that the phenotypic heterogeneity of human cutaneous melanomas is related to their content of CD133+ cells. METHODS: We compared the percentages of CD133+ cells in 29 tumours from four classic types of melanoma: lentigo maligna melanoma (LMM), superficial spreading melanoma, nodular melanoma and acral lentiginous melanoma (ALM). Also, we compared the percentages of CD133+ cells in melanomas with different degrees of exposure to ultraviolet radiation: 16 melanomas from skin with chronic sun-induced damage and 13 melanomas from skin without such damage. RESULTS: We found a statistically significant increase of CD133+ cells in three different contexts: in melanomas arising on skin with signs of chronic sun-induced damage vs. nonexposed skin, in melanomas in situ vs. invasive melanomas, and in LMM vs. ALM. The proportions of CD133+ cells did not differ among samples of normal skin with different degrees of sun exposure. A distinct subpopulation of CD133+CXCR4+ cancer stem cells (CSCs) was identified and shown to be related to the invasive phenotype of the tumours. CONCLUSIONS: Here, we provide evidence showing, for the first time, that an increase in the CD133+ cell content is associated both with melanomas arising on skin with signs of chronic sun-induced damage and in melanomas in situ with better prognosis. Moreover, our study further confirms the existence of a subpopulation of CD133+CXCR4+ CSCs in cutaneous melanomas with invasive phenotype and poor prognosis.

Cutaneous mucormycosis infection by Absidia in two consecutive liver transplant patients.

Mucormycosis, although an infrequent fungal infection, has a high mortality in patients undergoing orthotopic liver transplantation. We present two cases of cutaneous Absidia mucormycosis in two successive patients undergoing liver transplantation in our hospital. In our literature search, we encountered only one published case of Absidia infection in liver transplantation.

A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹° to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient.

Plan de cuidados en autosondaje: a propósito de un caso / No disponible

Basándonos en la oferta de una adecuada atención enfermera, centrada en la personalización y en la continuidad con planes de cuidados estandarizados, mostramos mediante el presente trabajo un ejemplo de intervención enfermera en Autosondaje. Entre los nuevos retos de reorientación en el cuidado para Enfermería, se encuentra el de utilizar un lenguaje común estándar, y que permita hacer visible la labor autónoma de la enfermera. En nuestro entorno asistencial del ASNC, se viene aplicando el modelo de Enfermería de Virginia Henderson, que define la salud como un estado de completa autonomía (independencia) del usuario. La enfermera interviene supliendo aquellas necesidades alteradas (manifestaciones de dependencia o problemas de autonomía), haciendo por el paciente aquello que él mismo realizaría si tuviera la fuerza, conocimiento o voluntad necesarias; y en caso de problema de autonomía, supliendo totalmente la necesidad en cuestión. Por otro lado, el plan de cuidados se erige como el mejor método para comprobar la evolución del problema en cuestión, haciendo medibles los resultados en salud según la objetivación de indicadores del resultado en base a una escala Likert. Todos los conceptos mencionados quedan plasmados en el trabajo que desarrollamos a continuación (AU)

We build on the offer of an adequate nursing attention, centered in the personalization and in the continuity with plans of standardized cares, we show through this research an example of nursing intervention in Selfsounding. Among the new challenges of redirection in the nursing cares, it is the one of using a common standard language, and which allows being visible the autonomous work of the nurse. In our assistance environment in the ASNC, the Virginia Henderson model of nursing is being applied, which defines the health as a state of complete autonomy (independence) of the user. The nurse takes part making up for those altered needs (a show of dependence or autonomy problems), making for the patient what they self would carry out if they had the strength, knowledge or the necessary will; and in the event of autonomy problem, totally making up for the need matter. On the other hand, the care plan is erected as the best method to check the evolution of the problem matter, making the results measurable in health according to the objectivation of the indicators of the result following a Likert scale. All the mentioned concepts are represented in the research that we develop next (AU)

Transcriptomal profiling of the cellular response to DNA damage mediated by Slug (Snai2).

Snai2-deficient cells are radiosensitive to DNA damage. The function of Snai2 in response to DNA damage seems to be critical for its function in normal development and cancer. Here, we applied a functional genomics approach that combined gene-expression profiling and computational molecular network analysis to obtain global dissection of the Snai2-dependent transcriptional response to DNA damage in primary mouse embryonic fibroblasts (MEFs), which undergo p53-dependent growth arrest in response to DNA damage. Although examination of the response showed that overall expression of p53 target gene expression patterns was similarly altered in both control and Snai2-deficient cells, we have identified and validated candidate Snai2 target genes linked to Snai2 gene function in response to DNA damage. This work defines for the first time the effect of Snai2 on p53 target genes in cells undergoing growth arrest, elucidates the Snai2-dependent molecular network induced by DNA damage, points to novel putative Snai2 targets, and suggest a mechanistic model, which has implications for cancer management.

Sustained leukaemic phenotype after inactivation of BCR-ABLp190 in mice.

Pharmacological inactivation of cancer genes or products is being used as a strategy for therapy in oncology. To investigate the potential role of BCR-ABLp190 cessation in leukaemia development, we generated mice carrying a tetracycline-repressible BCR-ABLp190 transgene. These mice were morphologically normal at birth, and developed leukaemias. Disease was characterized by the presence of B-cell blasts co-expressing myeloid markers, reminiscent of the human counterpart. BCR-ABLp190 activation can initiate leukaemia in both young and adult mice. Transitory expression of BCR-ABLp190 is enough to develop leukaemia. Suppression of the BCR-ABLp190 transgene in leukaemic CombitTA-p190 mice did not rescue the malignant phenotype, indicating that BCR-ABLp190 is not required to maintain the disease in mice. Similar results were obtained by inactivation of BCR-ABLp190 with STI571 (Gleevec; Novartis, East Hanover, NJ, USA) in leukaemic CombitTA-p190 mice. However, gradual suppression of BCR-ABLp190 in leukaemic CombitTA-p190 mice identified a minimum level of BCR-ABLp190 expression necessary to revert the specific block in B-cell differentiation in the leukaemic cells. Overall, the findings indicate that BCR-ABLp190 appears to cause epigenetic and/or genetic changes in tumour-maintaining cells that render them insensitive to BCR-ABLp190 inactivation.

Características clínico-funcionales en pacientes fumadores con infarto agudo de miocardio y su situación a los 5 años / Clinical-functional characteristics in patients who smoke with acute myocardial infarctionand their situation at 5 years

Introducción y objetivos: Valorar características y efectividad delas recomendaciones de deshabituación tabáquica de fumadores tras un infarto agudo de miocardio a 5 años. Material y métodos: Se analizaron 310 infartos ocurridos en 1998 de éstos se analizaron 64 fumadores activos, se realizó seguimiento durante 5 años, analizándose: sexo, edad, factores de riesgo, características del IAM, dependencia nicotínica (test de Fagerström) y motivación(test de Richmond) de los que abandonaron el tabaco y de los que continuaban. Las variables cuantitativas con distribución normal se expusieron con la media, con la mediana si la distribución no fue normal. La comparación de variables cualitativas continuas se utilizaron test paramétricos y no paramétricos (χ2 y U de Mann-Whitney). Resultados: Tras el evento cardiológico a los 5 años el 37,5% (24/64) continúan fumando y el 62,5% (40/64) abandonaron el tabáquico. Existió mayor abandono en pacientes con IAM anterolateral extenso y fracción de eyección (FE) moderadamente deprimida, (p = 0,05). No existiendo relación estadísticamente significativa para abandono o persistencia del hábito la presencia o no de otros factores de riesgo asociados, ni respecto a dependencia y motivación, ni entre edad de inicio (17,85 años vs 16,93 años), años de consumo (36,95 vs 49,17) y nº de cigarrillos/día consumidos (20,5 vs 21,25). Conclusiones: Existe relación con el cese del hábito tabáquico con las características del IAM, extensión de éste y FE, sin tener relación edad, dependencia, motivación factores de riesgo asociados, nº cigarrillos/día, edad de inicio, años de consumo (AU)

Introduction and objectives: Assess characteristics and effectiveness of tobacco dehabituation recommendations for smokers after acute myocardial infarction at 5 years. Material and methods: A total of 310 infarctions that occurred in 1998 were analyzed. Of these, 64 active smokers were followed-up for 5 years, analyzing: gender, age, risk factors, AMI characteristics, nicotine dependence (Fagerstrom test) and motivation (Richmond test)for those who gave up smoking and those who continued. The quantitative variables with normal distribution were expressed with the mean, and with median if the distribution was not normal. Comparison of continuous qualitative variables was done with parametric and non-parametric tests (Mann-Whitney χ2 and U test).Results: At 5 years of the cardiological event, 37.5% (24/64) continued smoking and 62.5% (40/64) had given up smoking. There was greater abandonment in patients with extensive anterolateral AMI and moderately depressed ejection fraction (EF) (p = 0.05). There was no statistically significant relationship for abandonment or persistence of the habit, presence or not of other risk factors, or in regards to dependence and motivation, nor between onset age (17.85 years vs. 19.93 years), years of consumption (36.95 vs 49.17) and no. of cigarettes/day consumed(20.5 vs 21.25). Conclusions: There is a relationship with abandoning the smoking habit with the characteristics of AMI, its extension and EF, without any relationship to age, dependence, motivation, associated risk factor, no. of cigarettes/day, onset age, years of consumption(AU)