Tissue-Specific Differences of p53 Inhibition by Mdm2 and Mdm4

The function of the p53 tumor suppressor to inhibit proliferation or initiate apoptosis is often abrogated in tumor cells. Mdm2 and its homolog, Mdm4, are critical inhibitors of p53 that are often overexpressed in human tumors. In mice, loss of Mdm2 or Mdm4 leads to embryonic lethal phenotypes that are completely rescued by concomitant loss of p53. To examine the role of Mdm2 and Mdm4 in a temporal and tissue-specific manner and to determine the relationships of these inhibitors to each other, we generated conditional alleles. We deleted Mdm2 and Mdm4 in cardiomyocytes, since proliferation and apoptosis are important processes in heart development. Mice lacking Mdm2 in the heart were embryonic lethal and showed defects at the time recombination occurred. A critical number of cardiomyocytes were lost by embryonic day 13.5, resulting in heart failure. This phenotype was completely rescued by deletion of p53. Mice lacking Mdm4 in the heart were born at the correct ratio and appeared to be normal. Our studies provide the first direct evidence that Mdm2 can function in the absence of Mdm4 to regulate p53 activity in a tissue-specific manner. Moreover, Mdm4 cannot compensate for the loss of Mdm2 in heart development

Barrett's esophagus: Ten years of experience at a tertiary care hospital center in Mexico

Introduction: The prevalence of Barrett's esophagus has been calculated at between 1.3 and 1.6%. There is little information with respect to this in Mexico. Aim: To determine the frequency and characteristics of Barrett's esophagus in patients that underwent endoscopy at a national referral center, within a 10-year time frame. Material and methods: The databases of the pathology and gastrointestinal endoscopy departments of the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” were analyzed, covering the period of January 2002 to December 2012. Patients with a histologic diagnosis of Barrett's esophagus were included. The variables of age, sex, the presence of dysplasia/esophageal adenocarcinoma, Barrett's esophagus length, and follow-up were analyzed. Results: Of 43,639 upper gastrointestinal endoscopies performed, 420 revealed Barrett's esophagus, corresponding to a frequency of 9.6 patients for every 1,000 endoscopies. Of those patients, 66.9% (n = 281) were men, mean patient age ± SD was 57.2 ± 15.3 years, 223 patients (53%) presented with long-segment Barrett's esophagus, and 197 (47%) with short-segment Barrett's esophagus. Dysplasia was not present in 339 patients (80.7%). Eighty-one (19.3%) patients had some grade of dysplasia or cancer: 48/420 (11.42%) presented with low-grade dysplasia, 20/420 (4.76%) with high-grade dysplasia, and 13/420 (3.1%) were diagnosed with esophageal cancer arising from Barrett's esophagus. Mean follow-up time was 5.6 years. Conclusions: The frequency of Barrett's esophagus was 9.6 cases for every 1,000 upper gastrointestinal endoscopies performed. Dysplasia was not documented in the majority of the patients with Barrett's esophagus and they had no histopathologic changes during follow-up. A total of 19.3% of the patients presented with dysplasia or cancer

Esófago de Barrett: experiencia de 10 años en un centro de tercer nivel en México

Introducción: La prevalencia de esófago de Barrett (EB) se ha calculado entre el 1.3 y el 1.6%. En México existen pocos datos al respecto. Objetivo: Determinar la frecuencia y características del EB en pacientes sometidos a endoscopia en un centro de referencia nacional, en un periodo de 10 años. Material y métodos: Se analizaron bases de datos de los departamentos de Patología y Endoscopia Gastrointestinal del Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán» (INCMNSZ), en el periodo comprendido de enero del 2002 a diciembre del 2012. Se incluyó a pacientes con diagnóstico histológico de EB. Se analizaron edad, sexo, presencia de displasia/adenocarcinoma de esófago, longitud del EB y seguimiento. Resultados: Se realizaron 43,639 endoscopias de tubo digestivo superior, se incluyó a 420 pacientes con EB, lo que corresponde a una frecuencia de 9.6 pacientes por cada 1,000 estudios realizados. El 66.9% (n = 281) fueron hombres; la edad media ± DE fue de 57.2 ± 15.3 años; 223 pacientes (53%) presentaron EB de segmento largo y 197(47%) de segmento corto; 339 pacientes (80.7%) no presentaron displasia, 81(19.3%) tuvieron algún grado de displasia o cáncer; de estos, 48/420 (11.42%) displasia de bajo grado, 20/420 (4.76%) displasia de alto grado y 13/420 (3.1%) tuvieron el diagnóstico de cáncer esofágico originado en EB. El seguimiento promedio fue de 5.6 años. Conclusiones: La frecuencia de EB fue de 9.6 casos por cada 1,000 endoscopias de tubo digestivo superior. En la mayoría de los pacientes con EB no se documentó displasia y permanecieron sin cambios histopatológicos durante el seguimiento. El 19.3% de los pacientes presentaron displasia o cáncer

Long-distance correlations in TCABR biasing experiments

Long-distance correlations (LDCs) of plasma potential fluctuations in the plasma edge have been investigated in the TCABR tokamak in the regime of edge biasing H-mode using an array of multi-pin Langmuir probes. This activity was carried out as part of the scientific programme of the 4th IAEA Joint Experiment (2009). The experimental data confirm the effect of amplification of LDCs in potential fluctuations during biasing recently observed in stellarators and tokamaks. For long toroidal distances between probes, the cross-spectrum is concentrated at low frequencies f < 60 kHz with peaks at f < 5 kHz, f = 13-15 kHz and f similar to 40 kHz and low wave numbers with a maximum at k = 0. The effects of MHD activity on the LDCs in potential fluctuation are investigated.FINEPFINEPFAPESPFAPESPIAEA (International Atomic Energy Agency)IAEA (International Atomic Energy Agency)National Fusion NetworkNational Fusion Networ

Dual antiplatelet therapy duration after coronary stenting in clinical practice: results of an EAPCI survey

Aims: Our aim was to report on a survey initiated by the EuropeanAssociation of Percutaneous Cardiovascular Interventions (EAPCI) concerning opinion on the evidence relating to dual antiplatelet therapy (DAPT) duration after coronary stenting.Methods and results: Results from three randomised clinical trials were scheduled to be presented at the American Heart Association Scientific Sessions 2014 (ARIA 2014). A web-based survey was distributed to all individuals registered in the EuroIntervention mailing list (n=15,200) both before and after ARIA 2014. A total of 1,134 physicians responded to the first (i.e., before AHA 2014) and 542 to the second (i.e., after ARIA 2014) survey. The majority of respondents interpreted trial results consistent with a substantial equipoise regarding the benefits and risks of an extended versus a standard DAPT strategy. Two respondents out of ten believed extended DAFT should be implemented in selected patients. After ARIA 2014, 46.1% of participants expressed uncertainty about the available evidence on DAFT duration, and 40.0% the need for clinical guidance.Conclusions: This EAPCI survey highlights considerable uncertainty within the medical community with regard to the optimal duration of DAFT after coronary stenting in the light of recent reported trial results. Updated recommendations for practising physicians to guide treatment decisions in routine clinical practice should be provided by international societies