A novel role for ATF3 is identified in acinar-to–duct cell metaplasia during pancreatic injury. ATF3 targets transcriptional regulators that affect acinar cell fate and reduces the severity of pancreatic injury. However, by doing so, ATF3 may also increase the susceptibility for progression to pancreatic adenocarcinoma.
Background
Evidence supports establishing a continuum of care from stroke rehabilitation (SR) to cardiac rehabilitation programs (CRPs). It is not known to what extent people poststroke are being integrated. This study aimed to determine the proportion of CRPs that accept referrals poststroke, barriers/facilitators, and eligibility criteria.
Methods
A web-based questionnaire was sent to CRPs across Canada.
Results
Of 160 questionnaires sent, 114 representatives (71%) of 130 CRPs responded. Of respondents, 65% (n = 74) reported accepting people with a diagnosis of stroke and doing so for a median of 11 years, 11 offering stroke-specific classes and an additional 6 planning inclusion. However, 62.5% of CRPs reported that < 11 patients participated in the last calendar year despite 88.5% reporting no limit to the number they could enroll. Among CRPs, 25% accepted only patients with concurrent cardiac diagnoses, living in the community (47.8%), and without severe mobility (70.1%), communication (80.6%), or cognitive (85.1%) deficits. The 2 most influential barriers and facilitators among all CRPs were funding and staffing. The fourth greatest barrier was lack of poststroke referrals, and third to sixth facilitators were SR/CRP collaboration to ensure appropriate referrals (third) and to increase referrals (sixth), toolkits for prescribing resistance (fourth), and aerobic training (fifth). CRP characteristics associated with accepting stroke were a hybrid program model, a medium program size, and having a falls prevention component.
Conclusions
Most CRPs accept patients poststroke, but few participate. Therefore, establishing SR/CRP partnerships to increase appropriate referrals, using a toolkit to help operationalize exercise components, and allocating funding/resources to CRPs may significantly increase access to secondary prevention strategies.
The unfolded protein response (UPR) is activated in pancreatic pathologies and suggested as a target for therapeutic intervention. In this study, we examined Activating Transcription Factor 3 (ATF3), a mediator of the UPR which promotes acinar-to-ductal metaplasia (ADM) in response to pancreatic injury. Since ADM is an initial step in the progression to pancreatic ductal adenocarcinoma (PDAC), we hypothesized ATF3 is required for initiation and progression of PDAC. We generated mice carrying a germ line mutation of Atf3 (Atf3-/-) combined with acinarspecific induction of oncogenic KRAS (Ptf1acreERT/+KrasLSL-G12D). Atf3-/-mice with (termed APK) and without KRASG12D were exposed to cerulein-induced pancreatitis. In response to recurrent pancreatitis, Atf3-/-mice showed decreased ADM and enhanced regeneration based on morphological and biochemical analysis. Similarly, an absence of ATF3 reduced spontaneous pancreatic intraepithelial neoplasia formation and PDAC in Ptf1acreERT/+KrasLSL-G12D mice. In response to injury, KRASG12D bipassed the requirement for ATF3 with a dramatic loss in acinar tissue and PanIN formation observed regardless of ATF3 status. However, unlike Ptf1acreERT/+KrasLSL-G12D mice, APK mice exhibited a cachexia-like phenotype, did not progress through to PDAC, and showed altered pancreatic fibrosis and immune cell infiltration. These findings suggest a complex, multifaceted role for ATF3 in pancreatic cancer pathology..
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