Rapid development of intestinal cell damage following severe trauma: a prospective observational cohort study

Introduction Loss of intestinal integrity has been implicated as an important contributor to the development of excessive inflammation following severe trauma. Thus far, clinical data concerning the occurrence and significance of intestinal damage after trauma remain scarce. This study investigates whether early intestinal epithelial cell damage occurs in trauma patients and, if present, whether such cell injury is related to shock, injury severity and the subsequent inflammatory response. Methods Prospective observational cohort study in 96 adult trauma patients. Upon arrival at the emergency room (ER) plasma levels of intestinal fatty acid binding protein (i-FABP), a specific marker for damage of differentiated enterocytes, were measured. Factors that potentially influence the development of intestinal cell damage after trauma were determined, including the presence of shock and the extent of abdominal trauma and general injury severity. Furthermore, early plasma levels of i-FABP were related to inflammatory markers interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP). Results Upon arrival at the ER, plasma i-FABP levels were increased compared with healthy volunteers, especially in the presence of shock (P < 0.01). The elevation of i-FABP was related to the extent of abdominal trauma as well as general injury severity (P < 0.05). Circulatory i-FABP concentrations at ER correlated positively with IL-6 and PCT levels at the first day (r2 = 0.19; P < 0.01 and r2 = 0.36; P < 0.001 respectively) and CRP concentrations at the second day after trauma (r2 = 0.25; P < 0.01). Conclusions This study reveals early presence of intestinal epithelial cell damage in trauma patients. The extent of intestinal damage is associated with the presence of shock and injury severity. Early intestinal damage precedes and is related to the subsequent developing inflammatory response

Exciton diffusion in two-dimensional metal-halide perovskites

Two-dimensional layered perovskites are attracting increasing attention as more robust analogues to the conventional three-dimensional metal-halide perovskites for both light harvesting and light emitting applications. However, the impact of the reduced dimensionality on the optoelectronic properties remains unclear, particularly regarding the spatial dynamics of the excitonic excited state within the two-dimensional plane. Here, we present direct measurements of exciton transport in single-crystalline layered perovskites. Using transient photoluminescence microscopy, we show that excitons undergo an initial fast diffusion through the crystalline plane, followed by a slower subdiffusive regime as excitons get trapped. Interestingly, the early intrinsic diffusivity depends sensitively on the choice of organic spacer. A clear correlation between lattice stiffness and diffusivity is found, suggesting exciton–phonon interactions to be dominant in the spatial dynamics of the excitons in perovskites, consistent with the formation of exciton–polarons. Our findings provide a clear design strategy to optimize exciton transport in these systemsThis work has been supported by the Spanish Ministry of Economy and Competitiveness through The “María de Maeztu” Program for Units of Excellence in R&D (MDM-2014-0377). M.S. acknowledges the financial support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/IN17/11620040. M.S. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 713673. F.P. acknowledges support from the Spanish Ministry for Science, Innovation, and Universities through the state program (PGC2018-097236-A-I00) and through the Ramón y Cajal program (RYC-2017-23253), as well as the Comunidad de Madrid Talent Program for Experienced Researchers (2016-T1/IND-1209). N.A., M.M. and R. D.B. acknowledges support from the Spanish Ministry of Economy, Industry and Competitiveness through Grant FIS2017-86007-C3-1-P (AEI/FEDER, EU). E.P. acknowledges support from the Spanish Ministry of Economy, Industry and Competitiveness through Grant FIS2016-80434-P (AEI/FEDER, EU), the Ramón y Cajal program (RYC-2011- 09345) and the Comunidad de Madrid through Grant S2018/ NMT-4511 (NMAT2D-CM). S.P. acknowledges financial support by the VILLUM FONDEN via the Centre of Excellence for Dirac Materials (Grant No. 11744

Hemolysis results in impaired intestinal microcirculation and intestinal epithelial cell injury

AIM: To study the effect of circulating cell-free oxyhemoglobin (FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model

Cloning and Expression of an Oligopeptidase, PepO, with Novel Specificity from Lactobacillus rhamnosus HN001 (DR20)

Oligopeptidases of starter and nonstarter lactic acid bacteria contribute to the proteolytic events important in maturation and flavor development processes in cheese. This paper describes the molecular cloning, expression, and specificity of the oligopeptidase PepO from the probiotic nonstarter strain Lactobacillus rhamnosus HN001 (DR20). The pepO gene encodes a protein of 70.9 kDa, whose primary sequence includes the HEXXH motif present in certain classes of metallo-oligopeptidases. The pepO gene was cloned in L. rhamnosus HN001 and overexpressed in pTRKH2 from its own promoter, which was mapped by primer extension. It was further cloned in both pNZ8020 and pNZ8037 and overexpressed in Lactococcus lactis subsp. cremoris NZ9000 from the nisA promoter. The purified PepO enzyme demonstrated unique cleavage specificity for α(s1)-casein fragment 1–23, hydrolyzing the bonds Pro-5-Ile-6, Lys-7-His-8, His-8-Gln-9, and Gln-9-Gly-10. The impact of this enzyme in cheese can now be assessed

Different pasts for different political folk: Political orientation predicts collective nostalgia content

Collective nostalgia is a bittersweet emotion that reflects sentimental longing for valued aspects of the past of one’s group. Given that conservatism is typically associated with a general desire to preserve the societal status quo or return society to its traditional way of being, nostalgia has been theorized to be characteristic of those on the political right (i.e., conservatives). In the current work, we proposed and tested the hypothesis that collective nostalgia is experienced by both conservatives and liberals, but the content of their nostalgizing differs. Across three studies in three socio-political contexts—United States (Study 1, MTurk, N = 352), Canada (Study 2, student sample, N = 154), and England (Study 3, online panel, N = 2,345)—we found that both conservatives and liberals experienced collective nostalgia for a more homogenous and open society. However, conservatives experienced more homogeneity-focused collective nostalgia, whereas liberals experienced more openness-focused collective nostalgia. Replicating previous findings, homogeneity-focused nostalgia emerged as a positive, whereas openness-focused nostalgia emerged as a negative, predictor of intergroup attitudes. The results have both theoretical and practical significance for understanding political attitudes and behaviors. To the point, variance in the conservative and liberal political agendas is, in part, a function of a difference in their respective predisposition to nostalgize about and thus desire the return of a particular aspect of the in-group’s past

Diagnostic potential of plasma biomarkers and exhaled volatile organic compounds in predicting the different stages of acute mesenteric ischaemia:Protocol for a multicentre prospective observational study (TACTIC study)

Introduction Acute mesenteric ischaemia (AMI) is a life-threatening condition with short-term mortality of up to 80%. The diagnosis of AMI has remained troublesome due to the non-specific clinical presentation, symptoms and laboratory findings. Early unambiguous diagnosis of AMI is critical to prevent progression from reversible to irreversible transmural intestinal damage, thereby decreasing morbidity and improving survival. The present study aims to validate a panel of plasma biomarkers and investigate volatile organic compound (VOC) profiles in exhaled air as a tool to timely and accurately diagnose AMI. Methods and analysis In this international multicentre prospective observational study, 120 patients (&gt;18 years of age) will be recruited with clinical suspicion of AMI. Clinical suspicion is based on: (1) clinical manifestation, (2) physical examination, (3) laboratory measurements and (4) the physician's consideration to perform a CT scan. The patient's characteristics, repetitive blood samples and exhaled air will be prospectively collected. Plasma levels of mucosal damage markers intestinal fatty acid-binding protein and villin-1, as well as transmural damage marker smooth muscle protein 22-alpha, will be assessed by ELISA. Analysis of VOCs in exhaled air will be performed by gas chromatography time-of-flight mass spectrometry. Diagnosis of AMI will be based on CT, endovascular and surgical reports, clinical findings, and (if applicable) verified by histopathological examination. Ethics and dissemination The study protocol was approved by the Medical Research Ethics Committee (METC) of Maastricht University Medical Centre+ and Maastricht University (METC azM/UM), the Netherlands (METC19-010) and the Ethics Committee Research UZ/KU Leuven, Belgium (S63500). Executive boards and local METCs of other Dutch participating centres Gelre Ziekenhuizen (Apeldoorn), Medisch Spectrum Twente (Enschede), and University Medical Centre Groningen have granted permission to carry out this study. Study results will be disseminated via open-access peer-reviewed scientific journals and national/international conferences. Trial registration number NCT05194527.</p

Protection against early intestinal compromise by lipid-rich enteral nutrition through cholecystokinin receptors

Objective: Early gut wall integrity loss and local intestinal inflammation are associated with the development of inflammatory complications in surgical and trauma patients. Prevention of these intestinal events is a potential target for therapies aimed to control systemic inflammation. Previously, we demonstrated in a rodent shock model that lipid-rich enteral nutrition attenuated systemic inflammation and prevented organ damage through a cholecystokinin receptor-dependent vagal pathway. The influence of lipid-rich nutrition on very early intestinal compromise as seen after shock is investigated. Next, the involvement of cholecystokinin receptors on the nutritional modulation of immediate gut integrity loss and intestinal inflammation is studied. Design: Randomized controlled in vivo study. Setting: University research unit. Subjects: Male Sprague-Dawley rats. Interventions: Liquid lipid-rich nutrition or control low-lipid feeding was administered per gavage before hemorrhagic shock. Cholecystokinin receptor antagonists were used to investigate involvement of the vagal antiinflammatory pathway. Measurements and Main Results: Gut permeability to horseradish peroxidase increased as soon as 30 mins postshock and was prevented by lipid-rich nutrition compared with low-lipid (p <.01) and fasted controls (p <.001). Furthermore, lipid-rich nutrition reduced plasma levels of enterocyte damage marker ileal lipid binding protein at 60 mins (p <.05). Early gut barrier dysfunction correlated with rat mast cell protease plasma concentrations at 30 mins (r(s) = 0.67; p <.001) and intestinal myeloperoxidase levels at 60 mins (r(s) = 0.58; p <.05). Lipid-rich nutrition significantly reduced plasma rat mast cell protease (p <.01) and myeloperoxidase (p <.05) before systemic inflammation was detectable. Protective effects of lipid-rich nutrition were abrogated by cholecystokinin receptor antagonists (horseradish peroxidase; p <.05 and rat mast cell protease; p <.05). Conclusions: Lipid-rich enteral nutrition prevents early gut barrier loss, enterocyte damage, and local intestinal inflammation before systemic inflammation develops in a cholecystokinin receptor-dependent manner. This study identifies activation of the vagal antiinflammatory pathway with lipid-rich nutrition as a potential therapy in patients prone to develop a compromised gut. (Crit Care Med 2010; 38:1592-1597

Chylomicron formation and glucagon-like peptide 1 receptor are involved in activation of the nutritional anti-inflammatory pathway

Enteral administration of lipid-enriched nutrition effectively attenuates inflammation via a cholecystokinin (CCK)-mediated vagovagal anti-inflammatory reflex. Cholecystokinin release and subsequent activation of the vagus are dependent on chylomicron formation and associated with release of additional gut peptides. The current study investigates the intestinal processes underlying activation of the CCK-mediated vagal anti-inflammatory pathway by lipid-enriched nutrition. Rats and mice were subjected to hemorrhagic shock (HS) or endotoxemia, respectively. Prior to the experimental procedures, animals were fasted or fed lipid-enriched nutrition. Pluronic L-81 (L-81) was added to the feeding to investigate involvement of chylomicron formation in activation of mesenteric afferent fibers and the immune-modulating potential of lipid-enriched nutrition. Ob/Ob mice and selective receptor antagonists were used to study the role of leptin, glucagon-like peptide 1 and peptide YY in activation of the nutritional reflex. Electrophysiological analysis of mesenteric afferents in mice revealed that lipid-enriched nutrition-mediated neural activation was abrogated by L-81 (P<.05). L-81 blunted the beneficial effects of lipid-enriched nutrition on systemic inflammation and intestinal integrity in both species (all parameters, P<.01). Ob/Ob mice required a higher dose of nutrition compared with wild-type mice to attenuate plasma levels of TNF-alpha and ileum-lipid binding protein, a marker for enterocyte damage (both P<.01), suggesting a higher stimulation threshold in leptin-deficient mice. Administration of a glucagon-like peptide 1-receptor antagonist, but not leptin or peptide YY antagonists, suppressed the effects of lipid-enriched nutrition. These data indicate that chylomicron formation is essential and activation of the glucagon-like peptide 1-receptor is involved in activation of the nutritional anti-inflammatory pathway by lipid-enriched nutrition