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01 februari 2023, Item does not contain fulltext, BACKGROUND: Artificial intelligence (AI) is rapidly fuelling a fundamental transformation in the practice of pathology. However, clinical integration remains challenging, with no AI algorithms to date in routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience. METHODS: Perspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analysed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus. FINDINGS: Consensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AI's role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology. INTERPRETATION: This systematic consensus study details the expected short-to-mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AI's successful clinical implemen

Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of adipose-derived mesenchymal cells (ASCs) and ghrelin (GHR), a neuropeptide with neuroprotective, trophic, and developmental regulatory actions, on peripheral nerve regeneration in a model of severe nerve injury repaired with nerve conduits. Material and methods. The right sciatic nerves of 24 male Wistar rats were 10-mm transected unilaterally and repaired with Dl-lactic-epsilon-caprolactone conduits. Rats were then treated locally with saline, ASCs, or GHR. At 12 weeks post-surgery, we assessed limb function by measuring ankle stance angle and percentage muscle mass reduction and evaluated the histopathology, immunohistochemistry, ultrastructure, and morphometry of myelinated fibers. Main Results. Rats receiving GHR or ASCs showed no significant increased functional recovery in ankle stance angle (p=0.372) but a higher nerve area (p=0.015), myelin area (p=0.046) and number of myelinated fibers (p=0.012) in the middle and distal segments of operated sciatic nerves in comparison to saline-treated control animals. Conclusion. These results suggest that utilization of ghrelin or ASCs may improve nerve regeneration using Dl-lactic-epsilon-caprolactone conduits.

Background. Collagen-induced arthritis (CIA), a murine experimental disease model induced by immunization with type II collagen (CII), is used to evaluate novel therapeutic strategies for rheumatoid arthritis. Adult stem cell marker Musashi-1 (Msi1) plays an important role in regulating themaintenance and differentiation of stem/precursor cells.The objectives of this investigation were to performa morphological study of the experimental CIAmodel, evaluate the effect of TNF-blocker (etanercept) treatment, and determine the immunohistochemical expression of Msi1 protein. Methods. CIA was induced in 50 male DBA1/J mice for analyses of tissue and serum cytokine; clinical and morphological lesions in limbs; and immunohistochemical expression of Msi1. Results. Clinically, TNF-blocker treatment attenuated CIA on day 32 after immunization (p < 0.001). Msi1 protein expression was significantly higher in joints damaged by CIAthan in those with no lesions (p < 0.0001) and was related to the severity of the lesions (Spearman’s rho = 0.775, p = 0.0001). Conclusions. Treatment with etanercept attenuates osteoarticular lesions in the murine CIA model. Osteoarticular expression of Msi1 protein is increased in joints with CIA-induced lesion and absent in nonlesioned joints, suggesting that this protein is expressed when the lesion is produced in order to favor tissue repair.

RATIONALE:: Proliferation and migration of smooth muscle cells (SMCs) are key steps for the progression of atherosclerosis and restenosis. Cortistatin is a multifunctional neuropeptide belonging to the somatostatin family that exerts unique functions in the nervous and immune systems. Cortistatin is elevated in plasma of patients experiencing coronary heart disease and attenuates vascular calcification. OBJECTIVE:: To investigate the occurrence of vascular cortistatin and its effects on the proliferation and migration of SMCs in vitro and in vivo and to delimitate the receptors and signal transduction pathways governing its actions. METHODS AND RESULTS:: SMCs from mouse carotid and human aortic arteries and from human atherosclerotic plaques highly expressed cortistatin. Cortistatin expression positively correlated with the progression of arterial intima hyperplasia. Cortistatin inhibited platelet-derived growth factor-stimulated proliferation of human aortic SMCs via binding to somatostatin receptors (sst2 and sst5) and ghrelin receptor, induction of cAMP and p38-mitogen-activated protein kinase, and inhibition of Akt activity. Moreover, cortistatin impaired lamellipodia formation and migration of human aortic SMCs toward platelet-derived growth factor by inhibiting, in a ghrelin-receptor- dependent manner, Rac1 activation and cytosolic calcium increases. These effects on SMC proliferation and migration correlated with an inhibitory action of cortistatin on the neointimal formation in 2 models of carotid arterial ligation. Endogenous cortistatin seems to play a critical role in regulating SMC function because cortistatin-deficient mice developed higher neointimal hyperplasic lesions than wild-type mice. CONCLUSIONS:: Cortistatin emerges as a natural endogenous regulator of SMCs under pathological conditions and an attractive candidate for the pharmacological management of vascular diseases that course with neointimal lesion formation. © 2013 American Heart Associat

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Materials and Methods: Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. Results: PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p= 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function. Copyright: © 2009 O'Valle et al.