CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid–base homeostasis. Cftr has been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping Beauty DNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated ApcMin mice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftr is a tumor suppressor gene in the intestinal tract as Cftr mutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc+/+ mice aged to ~ 1 year, Cftr deficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftr mutant mice compared with wild-type controls, suggesting a potential role of Cftr in regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc+/+ Cftr knockout mice and identified sets of genes dysregulated in tumors including altered Wnt β-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease-free survival.
It is unclear which aspects of empathy are shared and which are uniquely affected in autism spectrum disorder (ASD) and conduct disorder (CD) as are the neurobiological correlates of these empathy impairments. The aim of this systematic review is to describe the overlap and specificity of motor, emotional, and cognitive aspects of empathy in children and adolescents with ASD or CD. Motor and cognitive empathy impairments are found in both ASD and CD, yet the specificity seems to differ. In ASD facial mimicry and emotion recognition may be impaired for all basic emotions, whereas in CD this is only the case for negative emotions. Emotional empathy and the role of attention to the eyes therein need further investigation. We hypothesize that impaired motor and cognitive empathy in both disorders are a consequence of lack of attention to the eyes. However, we hypothesize major differences in emotional empathy deficits between ASD and CD, probably due to emotional autonomic and amygdala hyper-responsivity in ASD versus hypo-responsivity in CD, both resulting in lack of attention to the eyes.
The antibacterial effect of a home-made raw garlic extract and commercial garlic tablets alone and in combination with antibiotics or omeprazole was determined against clinical isolates of Helicobacter pylori. MIC values of raw garlic extract and three types of commercial garlic tablets ranged from 10,000 to 17,500 mg/L. When MIC values of the commercial tablets were based on the allicin content, no differences between the three types were observed. The combination of garlic and omeprazole, studied with killing curves, showed a synergic effect which was concentration dependent. Further clinical evaluation of garlic in combination with the conventional agents for H. pylori treatment seems warranted.
Fast Exact Euclidean Distance (FEED) transformation is introduced, starting from the inverse of the distance transformation. The prohibitive computational cost of a naive implementation of traditional Euclidean Distance Transformation, is tackled by three operations: restriction of both the number of object pixels and the number of background pixels taken in consideration and pre-computation of the Euclidean distance. Compared to the Shih and Liu 4-scan method the FEED algorithm is often faster and is less memory consuming.
The direct visualisation of nerves and adjacent anatomical structures may make ultrasonography the preferred method for nerve localisation. In this prospective randomised study, we investigated whether, for distal sciatic nerve block in the popliteal fossa, an ultrasound guided technique would result in the use of less local anaesthetic without changing block characteristics and quality. Using electrical nerve stimulation or ultrasound guidance, the nerve was identified in two groups of 20 patients scheduled for lower limb surgery. Hereafter lignocaine 1.5% with adrenaline 5 μg/ml was injected. The attending anaesthesiologist assessed the injected volume. Significantly less local anaesthetic was injected in the ultrasound group compared to the nerve stimulation group (17 vs. 37 ml, P <0.001), while the overall success rate was increased (100% vs. 75%; P=0.017). We conclude that the use of ultrasound localisation for distal sciatic nerve block in the popliteal fossa reduces the required dose of local anaesthetic significantly, and is associated with a higher success rate compared to nerve stimulation without changing block characteristics.
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