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Abstract Nonalcoholic steatohepatitis (NASH) is triggered by hepatocyte death through activation of caspase 6, as a result of decreased adenosine monophosphate (AMP)-activated protein kinase-alpha (AMPKα) activity. Increased hepatocellular death promotes inflammation which drives hepatic fibrosis. We show that the nuclear-localized mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in NASH patients and in NASH diet fed male mice. The focus of this work is to investigate whether and how MKP1 is involved in the development of NASH. Under NASH conditions increased oxidative stress, induces MKP1 expression leading to nuclear p38 MAPK dephosphorylation and decreases liver kinase B1 (LKB1) phosphorylation at a site required to promote LKB1 nuclear exit. Hepatic deletion of MKP1 in NASH diet fed male mice releases nuclear LKB1 into the cytoplasm to activate AMPKα and prevents hepatocellular death, inflammation and NASH. Hence, nuclear-localized MKP1-p38 MAPK-LKB1 signaling is required to suppress AMPKα which triggers hepatocyte death and the development of NASH.

Abstract Background For adults, vacations represent a break from daily responsibilities of work – offering the opportunity to re-distribute time between sleep, sedentary behaviour, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) across the 24-h day. To date, there has been minimal research into how activity behaviour patterns change on vacation, and whether any changes linger after the vacation. This study examined how daily movement behaviours change from before, to during and after vacations, and whether these varied based on the type of vacation and vacation duration. Methods Data collected during the Annual Rhythms In Adults’ lifestyle and health (ARIA) study were used. 308 adults (mean age 40.4 years, SD 5.6) wore Fitbit Charge 3 fitness trackers 24 h a day for 13 months. Minute-by-minute movement behaviour data were aggregated into daily totals. Multi-level mixed-effects linear regressions were used to compare movement behaviours during and post-vacation (4 weeks) to pre-vacation levels (14 days), and to examine the associations with vacation type and duration. Results Participants took an average of 2.6 (SD = 1.7) vacations of 12 (SD = 14) days’ (N = 9778 days) duration. The most common vacation type was outdoor recreation (35%) followed by family/social events (31%), rest (17%) and non-leisure (17%). Daily sleep, LPA and MVPA all increased (+ 21 min [95% CI = 19,24] p

Abstract Background Weather is a potentially important influence on how time is allocated to sleep, sedentary behaviour and physical activity across the 24-h day. Extremes of weather (very hot, cold, windy or wet) can create undesirable, unsafe outdoor environments for exercise or active transport, impact the comfort of sleeping environments, and increase time indoors. This 13-month prospective cohort study explored associations between weather and 24-h movement behaviour patterns. Methods Three hundred sixty-eight adults (mean age 40.2 years, SD 5.9, 56.8% female) from Adelaide, Australia, wore Fitbit Charge 3 activity trackers 24 h a day for 13 months with minute-by-minute data on sleep, sedentary behaviour, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) collected remotely. Daily weather data included temperature, rainfall, wind, cloud and sunshine. Multi-level mixed-effects linear regression analyses (one model per outcome) were used. Results Ninety thousand eight hundred one days of data were analysed. Sleep was negatively associated with minimum temperature (-12 min/day change across minimum temperature range of 31.2 °C, p = 0.001). Sedentary behaviour was positively associated with minimum temperature (+ 12 min/day, range = 31.2 oC, p = 0.006) and wind speed (+ 10 min/day, range = 36.7 km/h, p

Introduction Pelvic exenteration (PE) surgery represents the only potentially curative treatment option for patients with locally advanced or recurrent rectal cancer (LARRC). Given the potential morbidity, whether or not PE should be recommended for an individual patient presents a major decisional conflict. This study aims to identify the outcomes of PE for which there is consensus among patients, carers and clinicians regarding their importance in guiding treatment decision-making, and to develop a risk prediction tool which predicts these outcomes.Methods and analysis This study will be conducted at a specialist PE centre, and employ a mixed-methods study design, divided into three distinct phases. In phase 1, outcomes of PE will be identified through a comprehensive systematic review of the literature (phase 1a), followed by exploration of the experiences of individuals who have undergone PE for LARRC and their carers (phase 1b, target sample size 10–20 patients and 5–10 carers). In phase 2, a survey of patients, their carers and clinicians will be conducted using Delphi methodology to explore consensus around the outcomes of highest priority and the level of influence each outcome should have on treatment decision-making. In phase 3 a, risk prediction tool will be developed using data from a single PE referral centre (estimated sample size 500 patients) to predict priority outcomes using multivariate modelling, and externally validated using data from an international PE collaboration.Ethics and dissemination Ethical approval has been granted for phases 1 and 2 (X22-0422 and 2022/ETH02659) and for maintenance of the database used in phase 3 (X13-0283 and HREC/13/RPAH/504). Informed consent will be obtained from participants in phases 1b and 2; a waiver of consent for secondary use of data in phase 3 will be sought. Study results will be submitted for publication in international and/or national peer reviewed journals.PROSPERO registration number CRD42022351909.

Abstract Background Pancreatic and oesophagogastric (OG) cancers have a dismal prognosis and high symptom burden, with supportive care forming an integral component of the care provided to patients. This study aimed to explore the supportive care experiences of patients and caregivers living with pancreatic and OG cancers in order to identify perceived opportunities for improvement. Methods Semi-structured individual interviews were conducted with people living with pancreatic and OG cancers, and their caregivers, across Victoria, Australia during 2020. Interviews were thematically analysed to identify common themes. Results Forty-one participants were interviewed, including 30 patients and 11 caregivers. Three overarching themes, each with multiple sub-themes, were identified: (i) inadequate support for symptoms and issues across the cancer journey (ii) caregiver’s desire for greater support, and (iii) a multidisciplinary care team is the hallmark of a positive supportive care experience. Generally, those who had access to a cancer care coordinator and/or a palliative care team recounted more positive supportive care experiences. Conclusion Unmet needs are prevalent across the pancreatic and OG cancer journey, with supportive care provided to varying levels of satisfaction. Greater awareness of and access to high-quality multidisciplinary support services is greatly desired by both patients with pancreatic and OG cancer and their caregivers.