PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Temporal profiling of an acute stress-induced behavioral phenotype in mice and role of hippocampal DRR1

Understanding the neurobiological mechanisms underlying the response to an acute stressor may provide novel insights into successful stress-coping strategies. Acute behavioral stress-effects may be restricted to a specific time window early after stress-induction. However, existing behavioral test batteries typically span multiple days or even weeks, limiting the feasibility for a broad behavioral analysis following acute stress. Here, we designed a novel comprehensive behavioral test battery in male mice that assesses multiple behavioral dimensions within a sufficiently brief time window to capture acute stress-effects and its temporal profile. Using this battery, we investigated the behavioral impact of acute social defeat stress (ASD) early thereafter (ASD-early, similar to 4 h), when circulating corticosterone levels were elevated, and late after stress-induction (ASD-late, similar to 8 h), when corticosterone were returned to timed control levels. ASD-early, but not ASD-late, displayed hippocampal-dependent cognitive impairments in the Y-maze and in the spatial object recognition test. The actin-binding protein (ABP) Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) has been described as resilience-promoting factor but the potential of DRR1 to curb stress-effects has not been investigated. Hippocampal DRR1 mRNA-expression was increased in ASD-early and ASD-late whereas DRR1-protein levels were increased only in ASDlate. We hypothesized that the absence of hippocampal DRR1 protein-upregulation in ASD-early caused the associated cognitive impairments. Hence, virus-mediated hippocampal DRR1-overexpression was induced as putative treatment, but cognitive deficits in ASD-early were not improved. We conclude that hippocampal DRR1-overexpression is insufficient to protect from the detrimental cognitive effects following acute social stress where perhaps a more global response in local actin dynamics, involving multiple stress-responsive ABPs that act synergistically, was warranted

Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines

Full text Embargoed until: 2015-07-30We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three-quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was associated with poorer melanoma-specific survival. In 47 melanoma cell lines homozygous loss, methylation or mutation of CDKN2A gene or loss of protein (p16(INK) (4A) ) predicted sensitivity to the CDK4/6 inhibitor PD0332991, while RB1 loss predicted resistance

Stream Nutrient Concentrations on the Windward Coast of Hawai‘I Island and Their Relationship to Watershed Characteristics.

v. ill. 23 cm.QuarterlyDissolved inorganic and organic nutrients and physiochemical parameters were measured in 24 Hawai‘i Island streams. Particulate nutrients and instantaneous nutrient and sediment fluxes were measured in half of these streams. Stream waters were dilute and slightly alkaline and had low concentrations of ammonium, orthophosphate, dissolved organic phosphorus, and total suspended solids. Particulate matter comprised 45%, 73%, and 28% of nitrogen, phosphorus, and carbon pools, respectively. Dissolved nitrogen was comprised primarily of organic nitrogen (54%) and nitrate (34%). In some streams, nitrate and total nitrogen concentrations were slightly elevated relative to Hawai‘i Department of Health (HDOH) water quality standards. Instantaneous nitrate yields for the streams plus 26 HDOH stations were calculated, and the average from the combined data set was 7.1 (SD 11.1) moles N day-1 km-2. Nitrate concentrations and yields were 2.1 and 3.5 times higher, respectively, in Kohala watersheds than in Mauna Kea watersheds. Regression analysis was used to evaluate whether water quality parameters are predicted by watershed area, mean annual rainfall, population density, or percentage of agricultural land. Many water quality parameters were not predicted by these variables. In Mauna Kea streams, concentrations of dissolved organic nitrogen and dissolved organic carbon increased with increasing watershed area, nitrate concentrations increased with increasing population density, and both specific conductivity and nitrate yield increased with increasing percentage of agricultural lands. In Kohala streams, nitrate concentrations and yields were not predicted by watershed characteristics. Overall, watershed characteristics, as quantified in this study, were not strong predictors of water quality

Variations of the Oxygen Minimum Zone of the Okhotsk Sea During the Last 50 ka as Indicated by Benthic Foraminiferal and Biogeochemical Data

Benthic foraminiferal and sediment biogeochemical data (total organic carbon, calcium carbonate and biogenic opal contents) in two cores (1265 and 1312 m water depths) from the southeastern Sakhalin slope and one core (839 m water depth) from the southwestern Kamchatka slope were investigated to reconstruct variations of the oxygen minimum zone during the last 50 ka in the Okhotsk Sea. The oxygen minimum zone was less pronounced during the maximal cooling in the MIS 2 that is suggested to be caused by a maximal expansion of sea ice cover, decrease of marine productivity and increase of production of the oxygenated Okhotsk Sea Intermediate Water (OSIW). A two-step-like strengthening of oxygen minimum zone during the warmings in the Termination Ia and Ib was linked to (1) enhanced oxygen consumption due to degradation of large amount of organic matter in the water column and bottom sediments, originated from increased marine productivity and supply of terrigenous material from the submerged northern shelves; (2) sea ice cover retreat and reduction of OSIW production; (3) freely inflow of the oxygen-depleted deep intermediate water mass from the North Pacific