Advocating for population health: The role of public health practitioners in the age of artificial intelligence.

Over the past decade, artificial intelligence (AI) has begun to transform Canadian organizations, driven by the promise of improved efficiency, better decision-making, and enhanced client experience. While AI holds great opportunities, there are also near-term impacts on the determinants of health and population health equity that are already emerging. If adoption is unregulated, there is a substantial risk that health inequities could be exacerbated through intended or unintended biases embedded in AI systems. New economic opportunities could be disproportionately leveraged by already privileged workers and owners of AI systems, reinforcing prevailing power dynamics. AI could also detrimentally affect population well-being by replacing human interactions rather than fostering social connectedness. Furthermore, AI-powered health misinformation could undermine effective public health communication. To respond to these challenges, public health must assess and report on the health equity impacts of AI, inform implementation to reduce health inequities, and facilitate intersectoral partnerships to foster development of policies and regulatory frameworks to mitigate risks. This commentary highlights AI's near-term risks for population health to inform a public health response.

RéSUMé: Au cours de la dernière décennie, l'intelligence artificielle (IA) a commencé à transformer les organismes canadiens en leur promettant une plus grande efficience, de meilleurs processus décisionnels et une expérience client enrichie. Bien qu'elle recèle d'immenses possibilités, l'IA aura des effets à court terme ­ qui se font d'ailleurs déjà sentir ­ sur les déterminants de la santé et sur l'équité en santé des populations. Si son adoption n'est pas réglementée, il se peut très bien que les iniquités en santé continuent d'être exacerbées par les préjugés, intentionnels ou non, ancrés dans les systèmes d'IA. Les nouvelles possibilités économiques pourraient être démesurément exploitées par les travailleurs et les travailleuses déjà privilégiés et par les propriétaires des systèmes d'IA, renforçant ainsi la dynamique de pouvoir existante. L'IA pourrait aussi nuire au bien-être des populations en remplaçant les interactions humaines au lieu de favoriser la connexité sociale. De plus, la mésinformation sur la santé alimentée par l'IA pourrait réduire l'efficacité des messages de santé publique. Pour relever ces défis, la santé publique devra évaluer et communiquer les effets de l'IA sur l'équité en santé, en modérer la mise en œuvre pour réduire les iniquités en santé, et faciliter des partenariats intersectoriels pour éclairer l'élaboration de politiques et de cadres réglementaires d'atténuation des risques. Le présent commentaire fait ressortir les risques à court terme de l'IA pour la santé des populations afin d'éclairer la riposte de la santé publique.

Evaluation of carbonic anhydrase IX as a potential therapeutic target in urothelial carcinoma.

OBJECTIVE: Carbonic anhydrase IX (CA9) is important in the regulation of intra- and extracellular pH in solid tumors, contributing to cell growth and invasion. In urothelial carcinoma (UC), CA9 has been identified as a urinary marker for disease detection, but its biologic role is unknown. To date, differential gene expression patterns of CA9 in various molecular subtypes and potential effects of CA9 inhibition in UC cells are unknown. We aimed to investigate the function of CA9 and the effects of CA9 inhibition in invasive UC. METHODS: Immunohistochemistry was used to assess CA9 expression in a cohort of 153 patients undergoing radical cystectomy. CA9 expression was correlated with molecular subtype by analysis of the TCGA data and of our own cohort of 223 patients with invasive UC receiving neoadjuvant chemotherapy. CA9 expression was assessed in a panel of 12 UC cell lines by Western Blot and qPCR, and multiple siRNAs were used to silence CA9 in 2 cell lines. Effects of CA9 silencing on cell growth, migration, and invasion were assessed. We also used the small molecule inhibitor U-104 to inhibit CA9 in vitro and in an orthotopic xenograft model. RESULTS: CA9 expression was higher in cancer tissue compared to benign urothelium and was particularly highly expressed in luminal papillary and basal squamous tumors. CA9 expression did not correlate with outcome after neoadjuvant chemotherapy and/or radical cystectomy. Silencing of CA9 by siRNA diminished invasion but did not induce a consistent change of cell growth and migration. Treatment with U-104 led to cell growth reduction only at high concentrations in vitro and failed to have a significant effect on tumor growth in vivo. CONCLUSIONS: The present study confirms over-expression of CA9 in UC and for the first time shows a correlation with molecular subtypes. However, CA9 expression showed no association with the outcome of patients with muscle invasive bladder cancer and inhibition of CA9 did not lead to a consistent inhibition of tumor growth. Based on these data, CA9 exhibits a role neither as a predictive or prognostic marker nor as a therapeutic target in invasive UC.

Microglial metabolic flexibility supports immune surveillance of the brain parenchyma.

Microglia are highly motile cells that continuously monitor the brain environment and respond to damage-associated cues. While glucose is the main energy substrate used by neurons in the brain, the nutrients metabolized by microglia to support surveillance of the parenchyma remain unexplored. Here, we use fluorescence lifetime imaging of intracellular NAD(P)H and time-lapse two-photon imaging of microglial dynamics in vivo and in situ, to show unique aspects of the microglial metabolic signature in the brain. Microglia are metabolically flexible and can rapidly adapt to consume glutamine as an alternative metabolic fuel in the absence of glucose. During insulin-induced hypoglycemia in vivo or in aglycemia in acute brain slices, glutaminolysis supports the maintenance of microglial process motility and damage-sensing functions. This metabolic shift sustains mitochondrial metabolism and requires mTOR-dependent signaling. This remarkable plasticity allows microglia to maintain their critical surveillance and phagocytic roles, even after brain neuroenergetic homeostasis is compromised.

Nanoscale Surveillance of the Brain by Microglia via cAMP-Regulated Filopodia.

Microglia, the brain's immune cells, maintain homeostasis and sense pathological changes by continuously surveying the parenchyma with highly motile large processes. Here, we demonstrate that microglia also use thin actin-dependent filopodia that allow fast nanoscale sensing within discrete regions. Filopodia are distinct from large processes by their size, speed, and regulation mechanism. Increasing cyclic AMP (cAMP) by activating norepinephrine Gs-coupled receptors, applying nitric oxide, or inhibiting phosphodiesterases rapidly increases filopodia but collapses large processes. Alternatively, Gi-coupled P2Y12 receptor activation collapses filopodia but triggers large processes extension with bulbous tips. Similar control of cytoskeletal dynamics and microglial morphology by cAMP is observed in ramified primary microglia, suggesting that filopodia are intrinsically generated sensing structures. Therefore, nanoscale surveillance of brain parenchyma by microglia requires localized cAMP increases that drive filopodia formation. Shifting intracellular cAMP levels controls the polarity of microglial responses to changes in brain homeostasis and alters the scale of immunosurveillance.