• Insulin protects acinar cells during pancreatitis by preserving glycolytic ATP supply to calcium pumps.

      Bruce, Jason I E; orcid: 0000-0002-4503-1981; email: jason.bruce@manchester.ac.uk; Sánchez-Alvarez, Rosa; Sans, Maria Dolors; orcid: 0000-0002-9271-2106; Sugden, Sarah A; Qi, Nathan; James, Andrew D; orcid: 0000-0002-2432-5948; Williams, John A (2021-07-19)
      Acute pancreatitis (AP) is serious inflammatory disease of the pancreas. Accumulating evidence links diabetes with severity of AP, suggesting that endogenous insulin may be protective. We investigated this putative protective effect of insulin during cellular and in vivo models of AP in diabetic mice (Ins2<sup>Akita</sup>) and Pancreatic Acinar cell-specific Conditional Insulin Receptor Knock Out mice (PACIRKO). Caerulein and palmitoleic acid (POA)/ethanol-induced pancreatitis was more severe in both Ins2<sup>Akita</sup> and PACIRKO vs control mice, suggesting that endogenous insulin directly protects acinar cells in vivo. In isolated pancreatic acinar cells, insulin induced Akt-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) which upregulated glycolysis thereby preventing POA-induced ATP depletion, inhibition of the ATP-dependent plasma membrane Ca<sup>2+</sup> ATPase (PMCA) and cytotoxic Ca<sup>2+</sup> overload. These data provide the first mechanistic link between diabetes and severity of AP and suggest that phosphorylation of PFKFB2 may represent a potential therapeutic strategy for treatment of AP.
    • 'Relieved to be seen'-patient and carer experiences of psychosocial assessment in the emergency department following self-harm: qualitative analysis of 102 free-text survey responses.

      Quinlivan, Leah M; orcid: 0000-0002-3944-3613; email: leah.quinlivan@manchester.ac.uk; Gorman, Louise; Littlewood, Donna L; Monaghan, Elizabeth; Barlow, Steven J; Campbell, Stephen M; Webb, Roger T; Kapur, Navneet (2021-05-23)
      <h4>Objectives</h4>We sought to explore patient and carer experiences of psychosocial assessments following presentations to hospital after self-harm.<h4>Design</h4>Thematic analysis of free-text responses to an open-ended online survey.<h4>Setting</h4>Between March and November 2019, we recruited 88 patients (82% women) and 14 carers aged ≥18 years from 16 English mental health trusts, community organisations, and via social media.<h4>Results</h4>Psychosocial assessments were experienced as helpful on some occasions but harmful on others. Participants felt better, less suicidal and less likely to repeat self-harm after good-quality compassionate and supportive assessments. However, negative experiences during the assessment pathway were common and, in some cases, contributed to greater distress, less engagement and further self-harm. Participants reported receiving negative and stigmatising comments about their injuries. Others reported that they were refused medical care or an anaesthetic. Stigmatising attitudes among some mental health staff centred on preconceived ideas over self-harm as a 'behavioural issue', inappropriate use of services and psychiatric diagnosis.<h4>Conclusion</h4>Our findings highlight important patient experiences that can inform service provision and they demonstrate the value of involving patients/carers throughout the research process. Psychosocial assessments can be beneficial when empathetic and collaborative but less helpful when overly standardised, lacking in compassion and waiting times are unduly long. Patient views are essential to inform practice, particularly given the rapidly changing service context during and after the COVID-19 emergency.