Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

‘I’m not a barcode or case file number’: understandings of perceived social support and belonging within disadvantaged adolescents and young adults

Perceived social support and a sense of belonging are thought to be protective factors against negative outcomes in adulthood that are commonly associated with childhood adversity. However, while this relationship is well established, very little is understood about how adolescents and young adults define these constructs themselves. This research aimed to examine adolescents’ and young adults’ understandings of perceived social support and sense of belonging, as well as their own understandings of their childhood experiences and current outcomes. Participants in the study were 275 adolescents and emerging adults aged between 17 and 24 (mean = 18.82, SD = 1.50), and included 177 females, 99 males, and 2 transgender participants, with 2 participants not disclosing their gender. Convenience sampling from a national group of young people accessing welfare service organisations within Australia was used. Qualitative data were obtained from 13 open-ended questions to an online survey. The study found that this group of adolescents and emerging adults with a history of childhood adversity understood social support and belonging as having someone who listened, as coming from people who surrounded them, and as impacted by their childhood experiences. We argue that support for this group of youth needs to revolve around building positive relationships in order to maximise resilience and well-being outcomes.Ian Goodwin-Smith, Kathleen Hill, Clemence Due, Michelle Waterford, Tatiana Corrales, Leanne Wood, Todd Yourell and Coco H

Does Public Accountability Work? : An Assessment Tool

In recent years, there has been a drive to strengthen existing public accountability arrangements and to design new ones. This prompts the question whether accountability arrangements actually work. In the existing literature, both accountability ‘deficits’ and ‘overloads’ are alleged to exist. However, owing to the lack of a cogent yardstick, the debate tends to be impressionistic and event‐driven. In this article we develop an instrument for systematically assessing public accountability arrangements, drawing on three different normative perspectives. In the democratic perspective, accountability arrangements should effectively link government actions to the ‘democratic chain of delegation’. In the constitutional perspective, it is essential that accountability arrangements prevent or uncover abuses of public authority. In the learning perspective, accountability is a tool to make governments effective in delivering on their promises. We demonstrate the use of our multicriteria assessment tool in an analysis of a new accountability arrangement: the boards of oversight of agencies