Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.      

The Impact of Behavioral Feeding Intervention on Health Care Utilization

This study examined health care utilization pre- and post-referral to a behaviorally based treatment program for feeding difficulties in children. Physician contacts and associated costs for a feeding clinic group (n = 490) and a group of matched population controls (n = 1,548) were examined across a 3-year period. Children with feeding difficulties had an increased frequency of physician visits and higher costs compared to controls. A subsample (n = 86) of clinic children revealed that successful behavioral feeding intervention resulted in a change in health care utilization, as demonstrated by a reduction in physician visits.     

Interplay between extracellular matrix components of Pseudomonas putida biofilms

The extracellular matrix of bacterial biofilms has at least two key functions: to serve as a structural scaffold for the multicellular community, and to play a protective role against external stress. In this work, we report a compensatory effect whereby Pseudomonas putida reacts to the lack of either of the two main surface proteins involved in biofilm formation, LapA and LapF, by increasing expression and production of a species-specific EPS. Elevated levels of the second messenger molecule cyclic di-GMP alter the balance of extracellular matrix components, and the phenotypes of lapA and lapF mutants under these conditions are indicative of direct interactions taking place between large secreted proteins and exopolysaccharides. Our data suggest the existence of a mechanism by which bacteria would sense alterations in the composition of the extracellular matrix, leading to changes in expression of the different elements.     

Characterization and Local Emission Sources for Ammonia in an Urban Environment

Ammonia levels were evaluated in the urban environment of Madrid City, Spain. A total of 110 samplers were distributed throughout the city. Vehicle traffic density, garbage containers and sewers were identified as local emission sources of ammonia. The average ammonia concentrations were 4.66?±?2.14 µg/m³ (0.39–11.23 µg/m³ range) in the winter and 5.30?±?1.81 µg/m³ (2.33–11.08 µg/m³ range) in the summer. Spatial and seasonal variations of ammonia levels were evaluated. Hotspots were located in the south and center of Madrid City in both winter and summer seasons, with lower ammonia concentrations located in the north (winter) and in the west and east (summer). The number of representative points that were needed to establish a reliable air quality monitoring network for ammonia was determined using a combined clustering and kriging approach. The results indicated that 40 samplers were sufficient to provide a reliable estimate for Madrid City.     

Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up

Purpose

Brugada syndrome is a hereditary disease linked with an increased risk of sudden death that may require an implantable cardioverter-defibrillator (ICD) in order to halt the arrhythmic events. The aim of this study was to identify possible triggers for appropriate ICD therapies in patients with Brugada syndrome, focusing on their past and current therapeutic profiles.

Methods

Thirty patients with high-risk Brugada syndrome, with ICD implanted at the Coimbra Hospital and University Center, were enrolled. Patients were questioned about their Brugada syndrome history, previous cardiac events, comorbidities, present and past medications, and physical activity. Patients were followed up during 5.8?±?5.3 years. The ICD was interrogated, and arrhythmic events and device therapies were recorded. The cohort who received appropriate ICD therapies was compared with the remaining patients to determine the potential link between clinical variables and potentially fatal arrhythmic events.

Results

More than half of the patients (53.3%) took at least one non-recommended drug, and 16.7% received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was a tendency for more appropriate ICD therapies in patients who took unsafe drugs (85.7 versus 45.5%, p?=?0.062), and the mean time between unsafe drug intake and appropriate ICD therapies was 3.8?±?7.5 days.

Conclusions

This study revealed that the medical community is still unaware of the pharmacological restrictions imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have a higher risk of ventricular arrhythmic events.