Gallstone pancreatitis vs alcohol-induced pancreatitis: does aetiology affect the extent of pancreatic necrosis?

This is the final version. Available on open access from Mattioli 1885 via the DOI in this recordBackground and aim: The impact of different aetiologies of acute pancreatitis on the development of pancreatic necrosis (PN) is unclear. This study assessed the extent and progression of pancreatic and peripan-creatic necrosis on the computed tomography (CT) scan of patients with gallstone (GP) and alcohol-induced (AIP) pancreatitis and evaluated their impact on disease severity. Methods: Patients ≥ 18-year-old with GP, AIP and PN on CT ( January 2010 – September 2018), were considered. The radiological extent of PN and clinical outcomes were analysed with a logistic regression model. Results: Eighty-one patients, 59 with GP, 22 with AIP, were included. GP had a larger extent of PN when the body and/or tail of the pancreas were involved (P = 0.009). Gallstone disease (P = 0.028) and higher American Society of Anesthetists scores (P = 0.043) were predictors of necrosis diffuse to different areas of the pancreas. Predictors of single/multiple organ failure were GP (P = 0.040), necrosis > 50% of the pancreas (P = 0.002) with a diffuse pattern (P = 0.004). Conclusions: Patients with GP had a wider extent of necrosis in the pancreatic body and/or tail. The onset of organ failure can be predicted in subjects with GP and larger amount of PN

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

How a universal health system reduces inequalities: lessons from England

Background: Provision of universal coverage is essential for achieving equity in healthcare, but inequalities still exist in universal healthcare systems. Between 2004/5 and 2011/12 the English NHS, which has provided universal coverage since 1948, made sustained efforts to reduce health inequalities by strengthening primary care. We provide the first comprehensive assessment of trends in socioeconomic inequalities of primary care access, quality and outcomes during this period. Methods: Whole-population small area longitudinal study, based on 32,482 neighbourhoods of approximately 1,500 people in England from 2004/5 to 2011/12. We measured slope indices of inequality in four indicators: (i) patients per family doctor (ii) primary care quality (iii) preventable emergency hospital admissions and (iv) mortality from conditions considered amenable to healthcare. Results: Between 2004/5 and 2011/12 there were larger absolute improvements on all indicators in more deprived neighbourhoods. The modelled gap between the most and least deprived neighbourhoods in England decreased by: 193 patients per family doctor (95% confidence interval 173 to 213), 3.29 percentage points of primary care quality (3.13 to 3.45), 0.42 preventable hospitalisations per 1,000 people (0.29 to 0.55) and 0.23 amenable deaths per 1,000 people (0.15 to 0.31). By 2011/12 inequalities in primary care supply and quality were almost eliminated but socio-economic inequality was still associated with 158,396 preventable hospitalisations and 37,983 deaths amenable to healthcare. Conclusions: Between 2004/5 and 2011/12 the NHS succeeded in substantially reducing socioeconomic inequalities in primary care access and quality but made only modest reductions in healthcare outcome inequalities

BioDeepTime : a database of biodiversity time series for modern and fossil assemblages

We thank the Paleosynthesis Project and the Volkswagen Stiftung for funding that supported this project (Az 96 796). M.C.R. acknowledges the German Research Foundation (DFG) for funding through the Cluster of Excellence ‘The Ocean Floor – Earth's Uncharted Interface’ (EXC 2077, grant no. 390741603). E.E.S. acknowledges funding from Leverhulme Trust grant RPG-201170, the Leverhulme Prize and the National Science Research Council grant NE/V011405/1. Q.J.L. and L.N. acknowledge support from the Youth Innovation Promotion Association (2019310) and the Chinese Academy of Sciences (CAS-WX2021SF-0205). A.M.P. acknowledges funding from the Leverhulme Trust through research grant RPG-2019-402. M.D. acknowledges funding from Leverhulme Trust through the Leverhulme Centre for Anthropocene Biodiversity (RC-2018-021) and a research grant (RPG-2019-402), and the European Union (ERC coralINT, 101044975). L. H. L. acknowledges funding from the European Research Council (macroevolution.abc ERC grant no. 724324). K.H.P acknowledges funding from the National Science Foundation Graduate Research Fellowship Program (DGE-2139841). H.H.M.H. acknowledges support from Peter Buck Postdoc Fellowship, Smithsonian Institution. A.T. acknowledges funding from the Slovak Research and Development Agency (APVV 22-0523) and the Slovak Scientific Grant Agency (VEGA 02/0106/23).Motivation We have little understanding of how communities respond to varying magnitudes and rates of environmental perturbations across temporal scales. BioDeepTime harmonizes assemblage time series of presence and abundance data to help facilitate investigations of community dynamics across timescales and the response of communities to natural and anthropogenic stressors. BioDeepTime includes time series of terrestrial and aquatic assemblages of varying spatial and temporal grain and extent from the present-day to millions of years ago. Main Types of Variables Included BioDeepTime currently contains 7,437,847 taxon records from 10,062 assemblage time series, each with a minimum of 10 time steps. Age constraints, sampling method, environment and taxonomic scope are provided for each time series. Spatial Location and Grain The database includes 8752 unique sampling locations from freshwater, marine and terrestrial ecosystems. Spatial grain represented by individual samples varies from quadrats on the order of several cm2 to grid cells of ~100 km2. Time Period and Grain BioDeepTime in aggregate currently spans the last 451?million years, with the 10,062 modern and fossil assemblage time series ranging in extent from years to millions of years. The median extent of modern time series is 18.7?years and for fossil series is 54,872?years. Temporal grain, the time encompassed by individual samples, ranges from days to tens of thousands of years. Major Taxa and Level of Measurement The database contains information on 28,777 unique taxa with 4,769,789 records at the species level and another 271,218 records known to the genus level, including time series of benthic and planktonic foraminifera, coccolithophores, diatoms, ostracods, plants (pollen), radiolarians and other invertebrates and vertebrates. There are to date 7012 modern and 3050 fossil time series in BioDeepTime. Software Format SQLite, Comma-separated values.Publisher PDFPeer reviewe

Identification of Prognostic Molecular Features in the Reactive Stroma of Human Breast and Prostate Cancer

Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

Effect of sarcopenia on survival of patients with cirrhosis: A meta-analysis

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized

Retigeric Acid B Exhibits Antitumor Activity through Suppression of Nuclear Factor-κB Signaling in Prostate Cancer Cells in Vitro and in Vivo

Previously, we reported that retigeric acid B (RB), a natural pentacyclic triterpenic acid isolated from lichen, inhibited cell growth and induced apoptosis in androgen-independent prostate cancer (PCa) cells. However, the mechanism of action of RB remains unclear. In this study, we found that using PC3 and DU145 cells as models, RB inhibited phosphorylation levels of IκBα and p65 subunit of NF-κB in a time- and dosage-dependent manner. Detailed study revealed that RB blocked the nuclear translocation of p65 and its DNA binding activity, which correlated with suppression of NF-κB-regulated proteins including Bcl-2, Bcl-xL, cyclin D1 and survivin. NF-κB reporter assay suggested that RB was able to inhibit both constitutive activated-NF-κB and LPS (lipopolysaccharide)-induced activation of NF-κB. Overexpression of RelA/p65 rescued RB-induced cell death, while knockdown of RelA/p65 significantly promoted RB-mediated inhibitory effect on cell proliferation, suggesting the crucial involvement of NF-κB pathway in this event. We further analyzed antitumor activity of RB in in vivo study. In C57BL/6 mice carrying RM-1 homografts, RB inhibited tumor growth and triggered apoptosis mainly through suppressing NF-κB activity in tumor tissues. Additionally, DNA microarray data revealed global changes in the gene expression associated with cell proliferation, apoptosis, invasion and metastasis in response to RB treatment. Therefore, our findings suggested that RB exerted its anti-tumor effect by targeting the NF-κB pathway in PCa cells, and this could be a general mechanism for the anti-tumor effect of RB in other types of cancers as well