Using our mini-brains: cerebral organoids as an improved cellular model for human prion disease

Neurodegenerative diseases are an ever-increasing burden in an aging society.Currently no cure is available for any of these diseases and treatment is based on managing symptoms.Despite many candidate therapeutics demonstrating promise in animal models,none has yet shown efficacy in human trials.It is self-evident that humans are different from the animals used to model our diseases,especially models that have been highly manipulated to generate a disease in an animal that does not naturally have such a disease.These differences are likely the reason for the failures of drug candidates in human trials but,until recently,human models of neurodegenerative diseases were lacking.The development of the human cerebral organoid model,by differentiating three-dimensional human neuronal tissue from pluripotent stem cells,represents a significant advance in studying human brain diseases.Cerebral organoids have been used to model Alzheimer’s disease,Parkinson’s disease,Down’s syndrome dementia and we have now shown they can be infected with human prions creating a new model of human prion diseases.     

Increased bladder permeability in interstitial cystitis/painful bladder syndrome

The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system.     

Endoscopy in Canada: Proceedings of the National Roundtable: Toronto,Ontario, February 7, 2014

This 2014 roundtable discussion, hosted by the Canadian Association of General Surgeons, brought together general surgeons and gastroenterologists with expertise in endoscopy from across Canada to discuss the state of endoscopy in Canada. The focus of the roundtable was the evaluation of the competence of general surgeons at endoscopy, reviewing quality assurance parameters for high-quality endoscopy, measuring and assessing surgical resident preparedness for endoscopy practice, evaluating credentialing programs for the endosuite and predicting the future of endoscopic services in Canada. The roundtable noted several important observations. There exist inadequacies in both resident training and the assessment of competency in endoscopy. From these observations, several collaborative recommendations were then stated. These included the need for a formal and standardized system of both accreditation and training endoscopists.     

C.B‐17 SCID mice develop epicardial calcinosis with unaltered cardiac function

Inbred mouse strains are the most widely used mammalian model organism in biomedical research owing to ease of genetic manipulation and short lifespan; however, each inbred strain possesses a unique repertoire of deleterious homozygous alleles that can make a specific strain more susceptible to a particular disease. In the current study, we report dystrophic cardiac calcinosis (DCC) in C.B‐17 SCID male mice at 10 weeks of age with no significant change in cardiac function. Acquisition of DCC was characterized by myocardial injury, fibrosis, calcification, and necrosis of the tissue. At 10 weeks of age, 38% of the C.B‐17 SCID mice from two different commercial colonies exhibited significant calcinosis on the ventricular epicardium, predominantly on the right ventricle. The frequency of calcinosis was more than 50% for mice obtained from Taconic's Cambridge City colony and 25% for mice obtained from Taconic's German Town colony. Interestingly, the DCC phenotype did not affect cardiac function at 10 weeks of age. No differences in echocardiography or electrocardiography were observed between the calcinotic and non‐calcinotic mice from either colony. Our findings suggest that C.B‐17 SCID mice exhibit DCC as early as 10 weeks of age with no significant impact on cardiac function. This strain of mice should be cautiously considered for the study of cardiac physiology.