Artificial intelligence research in Canadian hospitals: The development of metropolitan competencies.

This study explores the deployment of Artificial Intelligence (AI) in Canadian hospitals from 2000 to 2021, focusing on metropolitan areas. We investigate how local public and private research ecosystems and links to national and international AI hubs influence the adoption of AI in healthcare. Our analysis shows that AI research outputs from public institutions have a significant impact on AI competences in hospitals. In addition, collaborations between hospitals are critical to the successful integration of AI. Metropolitan areas such as Toronto, Montreal, and Vancouver are leading the way in AI deployment. These findings highlight the importance of local AI research capabilities and international hospital collaborations and provide guidance to policy-makers and health leaders to drive the diffusion of AI technology in healthcare.

Hypoxia-induced mobilization of NHE6 to the plasma membrane triggers endosome hyperacidification and chemoresistance.

The pH-dependent partitioning of chemotherapeutic drugs is a fundamental yet understudied drug distribution mechanism that may underlie the low success rates of current approaches to counter multidrug resistance (MDR). This mechanism is influenced by the hypoxic tumour microenvironment and results in selective trapping of weakly basic drugs into acidified compartments such as the extracellular environment. Here we report that hypoxia not only leads to acidification of the tumour microenvironment but also induces endosome hyperacidification. The acidity of the vesicular lumen, together with the alkaline pH of the cytoplasm, gives rise to a strong intracellular pH gradient that drives intravesicular drug trapping and chemoresistance. Endosome hyperacidification is due to the relocalization of the Na+/H+ exchanger isoform 6 (NHE6) from endosomes to the plasma membrane, an event that involves binding of NHE6 to the activated protein kinase C-receptor for activated C kinase 1 complex. These findings reveal a novel mechanism of hypoxia-induced MDR that involves the aberrant intracellular distribution of NHE6.

Simultaneous pH measurement in endocytic and cytosolic compartments in living cells using confocal microscopy.

Intracellular pH is tightly regulated and differences in pH between the cytoplasm and organelles have been reported(1). Regulation of cellular pH is crucial for homeostatic control of physiological processes that include: protein, DNA and RNA synthesis, vesicular trafficking, cell growth and cell division. Alterations in cellular pH homeostasis can lead to detrimental functional changes and promote progression of various diseases(2). Various methods are available for measuring intracellular pH but very few of these allow simultaneous measurement of pH in the cytoplasm and in organelles. Here, we describe in detail a rapid and accurate method for the simultaneous measurement of cytoplasmic and organellar pH by using confocal microscopy on living cells(3). This goal is achieved with the use of two pH-sensing ratiometric dyes that possess selective cellular compartment partitioning. For instance, SNARF-1 is compartmentalized inside the cytoplasm whereas HPTS is compartmentalized inside endosomal/lysosomal organelles. Although HPTS is commonly used as a cytoplasmic pH indicator, this dye can specifically label vesicles along the endosomal-lysosomal pathway after being taken up by pinocytosis(3,4). Using these pH-sensing probes, it is possible to simultaneously measure pH within the endocytic and cytoplasmic compartments. The optimal excitation wavelength of HPTS varies depending on the pH while for SNARF-1, it is the optimal emission wavelength that varies. Following loading with SNARF-1 and HPTS, cells are cultured in different pH-calibrated solutions to construct a pH standard curve for each probe. Cell imaging by confocal microscopy allows elimination of artifacts and background noise. Because of the spectral properties of HPTS, this probe is better suited for measurement of the mildly acidic endosomal compartment or to demonstrate alkalinization of the endosomal/lysosomal organelles. This method simplifies data analysis, improves accuracy of pH measurements and can be used to address fundamental questions related to pH modulation during cell responses to external challenges.

Multidisciplinary trauma team care in Kandahar, Afghanistan: current injury patterns and care practices.

Multidisciplinary trauma care systems have been shown to improve patient outcomes. Medical care in support of the global war on terror has provided opportunities to refine these systems. We report on the multidisciplinary trauma care system at the Role III Hospital at Kandahar Airfield, Afghanistan. We reviewed the Joint Trauma System Registry, Kandahar database from 1 October 2009 to 31 December 2010 and extracted data regarding patient demographics, clinical variables and outcomes. We also queried the operating room records from 1 January 2009 to 31 December 2010. In the study period of 1 October 2009 to 31 December 2010, 2599 patients presented to the trauma bay, with the most common source of injury being from Improvised Explosive Device (IED) blasts (915), followed by gunshot wounds (GSW) (327). Importantly, 19 patients with triple amputations as a result of injuries from IEDs were seen. 127 patients were massively transfused. The in-hospital mortality was 4.45%. From 1 January 2010 to 31 December 2010, 4106.24 operating room hours were logged to complete 1914 patient cases. The mean number of procedures per case in 2009 was 1.27, compared to 3.11 in 2010. Multinational, multidisciplinary care is required for the large number of severely injured patients seen at Kandahar Airfield. Multidisciplinary trauma care in Kandahar is effective and can be readily employed in combat hospitals in Afghanistan and serve as a model for civilian centres.