p53 loss and Kras mutation in an invasive murine model of colorectal cancer

For many years there have been many excellent mouse models of benign intestinal adenoma though not of later stage invasive disease. In this study we have attempted to generate a number of murine models that closely recapitulate the human disease by manipulating mutations that occur during colorectal cancer (CRC) progression. The p53 tumour suppressor gene is commonly mutated in sporadic CRC, though loss alone does not drive intestinal tumorigenesis. When we targeted p53 deletion to the adult murine intestine in concert with a single mutation in the Adenomatous Polyposis Coli (Apc) tumour suppressor gene, this led to an acceleration of tumorigenesis and an increase in the number of invasive tumours and more rarely metastasis. These invasive tumours closely resemble human tumours and importantly had many features of Epithelial to Mesenchymal Transition (EMT). Tumours in this background still formed at relatively long latencies suggesting other genetic events were occurring to drive the progression in the absence of p53. Up to 50% of colon cancers have a mutation in KRAS. Targeting mutant KrasG12D to the intestinal epithelium promotes hyperplasia though not tumorigenesis. In combination with Apc mutation there is an acceleration of tumorigenesis and a greater propensity to develop colonic tumours. To test whether Kras mutation caused a more marked phenotype in the background of p53 deficiency we generated VillinCreER+ Apcfl/+ p53fl/fl KrasG12D/+ mice. Remarkably these mice develop invasive and rarely metastatic tumours in as little as 50 days. Moreover even small tumours (less than 1mm) could be invasive. We believe these mouse models of invasive and metastatic intestinal adenocarcinoma will be an excellent tool to study the invasive and metastatic process in vivo. Moreover they should allow us to test the efficacy of drugs aimed to inhibit the invasion process

Erratum to: Arrhythmogenic right ventricular cardiomyopathy secondary to adipose infiltration as a cause of episodic collapse in a horse

[This corrects the article DOI: 10.1186/s13620-015-0052-3.]

Acute motor and sensory polyganglioradiculoneuritis in a cat: clinical and histopathological findings

Polyneuropathies can have a variety of clinical presentations and tend to be rare in cats. In this report we describe a 6-year-old domestic shorthair cat with an acute and rapidly progressive onset of lower motor neuron and sensory signs affecting the spinal and cranial nerves. Histopathological examination revealed moderate-to-severe multifocal inflammatory infiltrates at the ventral and dorsal nerve roots, and dorsal spinal ganglia at the level of the L4 and cauda equina. The type and severity of inflammation varied between nerve roots, being composed of mainly neutrophils in some and mainly lymphocytes and macrophages in others. Immunohistochemistry showed a combination of neutrophils, macrophages and lymphocytes infiltrating the nerve roots and ganglia. The majority of the lymphocytes were T lymphocytes; only a few B lymphocytes were seen. Neurons within the affected ganglia showed central chromatolysis and necrosis. Wallerian-like degeneration and demyelination were observed in the nerve roots. A sensory and motor polyganglioradiculoneuritis was diagnosed. An autoimmune process similar to the acute motor and sensory neuropathy subtype of Guillain–Barré syndrome in humans or an infection by an unidentified agent were considered most likely

Erratum to: Arrhythmogenic right ventricular cardiomyopathy secondary to adipose infiltration as a cause of episodic collapse in a horse

[This corrects the article DOI: 10.1186/s13620-015-0052-3.]

Documento internacional de consenso sobre apnea obstructiva del sueño.

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents)