Update: Induction of Inflammatory Bowel Disease in Immunodeficient Mice by Injection of Naïve CD4 T cells (T Cell Transfer Model of Colitis).

The intestinal inflammation induced by injection of naïve CD4 T cells into lymphocyte-deficient hosts (more commonly known as the T cell transfer model of colitis) shares many features of idiopathic inflammatory bowel disease (IBD) in humans, such as epithelial cell hyperplasia, crypt abscess formation, and dense lamina propria lymphocyte infiltration. As such, it provides a useful tool for studying mucosal immune regulation as it relates to the pathogenesis and treatment of IBD in humans. In the IBD model described here, colitis is induced in Rag (recombination-activating gene)-deficient mice by reconstitution of these mice with naïve CD4CD45RB T cells through adoptive T cell transfer.

Capillary washboarding during slow drainage of a frictional fluid.

Numerous natural and industrial processes involve the mixed displacement of liquids, gases and granular materials through confining structures. However, understanding such three-phase flows remains a formidable challenge, despite their tremendous economic and environmental impact. To unveil the complex interplay of capillary and granular stresses in such flows, we consider here a model configuration where a frictional fluid (an immersed sedimented granular layer) is slowly drained out of a horizontal capillary.

Frictional fluid instabilities shaped by viscous forces.

Multiphase flows involving granular materials are complex and prone to pattern formation caused by competing mechanical and hydrodynamic interactions. Here we study the interplay between granular bulldozing and the stabilising effect of viscous pressure gradients in the invading fluid. Injection of aqueous solutions into layers of dry, hydrophobic grains represent a viscously stable scenario where we observe a transition from growth of a single frictional finger to simultaneous growth of multiple fingers as viscous forces are increased.

MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T-cell responses.

Although intestinal epithelial cells (IECs) can express major histocompatibility complex class II (MHC II), especially during intestinal inflammation, it remains unclear if antigen presentation by IECs favors pro- or anti-inflammatory CD4 T-cell responses. Using selective gene ablation of MHC II in IECs and IEC organoid cultures, we assessed the impact of MHC II expression by IECs on CD4 T-cell responses and disease outcomes in response to enteric bacterial pathogens. We found that intestinal bacterial infections elicit inflammatory cues that greatly increase expression of MHC II processing and presentation molecules in colonic IECs.

Development and Validation of a Two-Step Predictive Risk Stratification Model for Coronavirus Disease 2019 In-hospital Mortality: A Multicenter Retrospective Cohort Study.

Objectives: An accurate prognostic score to predict mortality for adults with COVID-19 infection is needed to understand who would benefit most from hospitalizations and more intensive support and care. We aimed to develop and validate a two-step score system for patient triage, and to identify patients at a relatively low level of mortality risk using easy-to-collect individual information.

Design: Multicenter retrospective observational cohort study.

Dynamics of Dendritic Ice Freezing in Confinement.

We use high-speed photography to observe the dendritic freezing of ice between two closely spaced parallel plates. Measuring the propagation speeds of dendrites, we investigate whether there is a confinement-induced thermal influence upon the speed beyond that provided by a single surface. Plates of thermally insulating plastic and moderately thermally conductive glass are used alone and in combination, at temperatures between -10.

Identification of gut microbial species linked with disease variability in a widely used mouse model of colitis.

Experimental mouse models are central to basic biomedical research; however, variability exists across genetically identical mice and mouse facilities making comparisons difficult. Whether specific indigenous gut bacteria drive immunophenotypic variability in mouse models of human disease remains poorly understood. We performed a large-scale experiment using 579 genetically identical laboratory mice from a single animal facility, designed to identify the causes of disease variability in the widely used dextran sulphate sodium mouse model of inflammatory bowel disease.

CD4 T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival.

Interleukin (IL)-10 is considered a prototypical anti-inflammatory cytokine, significantly contributing to the maintenance and reestablishment of immune homeostasis. Accordingly, it has been shown in the intestine that IL-10 produced by Tregs can act on effector T cells, thereby limiting inflammation. Herein, we investigate whether this role also applies to IL-10 produced by T cells during central nervous system (CNS) inflammation.

Heat Emitting Damage in Skin: A Thermal Pathway for Mechanical Algesia.

Mechanical pain (or mechanical algesia) can both be a vital mechanism warning us for dangers or an undesired medical symptom important to mitigate. Thus, a comprehensive understanding of the different mechanisms responsible for this type of pain is paramount. In this work, we study the tearing of porcine skin in front of an infrared camera, and show that mechanical injuries in biological tissues can generate enough heat to stimulate the neural network.

Thermally activated intermittent dynamics of creeping crack fronts along disordered interfaces.

We present a subcritical fracture growth model, coupled with the elastic redistribution of the acting mechanical stress along rugous rupture fronts. We show the ability of this model to quantitatively reproduce the intermittent dynamics of cracks propagating along weak disordered interfaces. To this end, we assume that the fracture energy of such interfaces (in the sense of a critical energy release rate) follows a spatially correlated normal distribution.

Magnetic Janssen effect.

A pile of grains, even when at rest in a silo, can display fascinating properties. One of the most celebrated is the Janssen effect, named after the pioneering engineer who explained the pressure saturation at the bottom of a container filled with corn. This surprising behavior arises because of frictional interactions between the grains through a disordered network of contacts, and the vessel lateral walls, which partially support the weight of the column, decreasing its apparent mass.

Thermal dissipation as both the strength and weakness of matter. A material failure prediction by monitoring creep.

In any domain involving some stressed solids, that is, from seismology to general engineering, the strength of matter is a paramount feature to understand. We here discuss the ability of a simple thermally activated sub-critical model, which includes the auto-induced thermal evolution of cracks tips, to predict the catastrophic failure of a vast range of materials. It is in particular shown that the intrinsic surface energy barrier, for breaking the atomic bonds of many solids, can be easily deduced from the slow creeping dynamics of a crack.

Development and Validation of the COVID-NoLab and COVID-SimpleLab Risk Scores for Prognosis in 6 US Health Systems.

Purpose: Develop and validate simple risk scores based on initial clinical data and no or minimal laboratory testing to predict mortality in hospitalized adults with COVID-19.

Methods: We gathered clinical and initial laboratory variables on consecutive inpatients with COVID-19 who had either died or been discharged alive at 6 US health centers. Logistic regression was used to develop a predictive model using no laboratory values (COVID-NoLab) and one adding tests available in many outpatient settings (COVID-SimpleLab).

Learner Perceptions of Electronic End-of-shift Evaluations on An Emergency Medicine Clerkship.

Objectives: As students on an emergency medicine (EM) rotation work with different faculty on a daily basis, EM clerkships often incorporate an end-of-shift evaluation to capture sufficient student performance data. Electronic shift evaluations have been shown to increase faculty completion compliance. This study aimed to examine learner perceptions of their individualized feedback during an EM clerkship following the adoption of an electronic evaluation tool.

Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular Pathogen.

Individuals with malaria exhibit increased morbidity and mortality when infected with Gram-negative (Gr-) bacteria. To explore this experimentally, we performed co-infection of mice with Plasmodium chabaudi and Citrobacter rodentium, an extracellular Gr- bacterial pathogen that infects the large intestine. While single infections are controlled effectively, co-infection results in enhanced virulence that is characterized by prolonged systemic bacterial persistence and high mortality.

Multi-center implementation of automated age-adjusted D-dimer results reduces unnecessary PE imaging.

Background: Several previous studies have investigated the clinical utility of age-adjusted D-dimer cutoffs for diagnosing pulmonary embolism (PE).

Objectives: We performed a pre/post implementation study, using data from a mid-Atlantic healthcare system comprising 6 hospitals and 400,000 ED visits to determine whether implementing age adjusted D-dimer cutoffs reduced the number of imaging tests performed.

Methods: Retrospective study of all patients who had a D-dimer performed during ED visits between September 2015 to September 2018.

How heat controls fracture: the thermodynamics of creeping and avalanching cracks.

While of paramount importance in material science, the dynamics of cracks still lacks a complete physical explanation. The transition from their slow creep behavior to a fast propagation regime is a notable key, as it leads to full material failure if the size of a fast avalanche reaches that of the system. We here show that a simple thermodynamics approach can actually account for such complex crack dynamics, and in particular for the non-monotonic force-velocity curves commonly observed in mechanical tests on various materials.

Why do intestinal epithelial cells express MHC class II?

Intestinal epithelial cells (IECs) constitute the border between the vast antigen load present in the intestinal lumen and the mucosal immune compartment. Their ability to express antigen processing and presentation machinery evokes the question whether IECs function as non-conventional antigen-presenting cells. Major histocompatibility complex (MHC) class II expression by non-haematopoietic cells, such as IECs, is tightly regulated by the class II transactivator (CIITA) and is classically induced by IFN-γ.

Understanding immune-microbiota interactions in the intestine.

The past two decades have seen an explosion in research that aims to understand how the dynamic interplay with the gut microbiota impacts host health and disease, establishing a role for the gut microbiota in a plethora of pathologies. Understanding how health-promoting microbiota are established and how beneficial host-microbiota interactions are maintained is of immense biomedical importance. Despite the enormous progress that has been made, our knowledge of the specific microbiota members that mediate these effects and the mechanisms underlying these interactions is rudimentary.

Continuously Sheared Granular Matter Reproduces in Detail Seismicity Laws.

We introduce a shear experiment that quantitatively reproduces the main laws of seismicity. By continuously and slowly shearing a compressed monolayer of disks in a ringlike geometry, our system delivers events of frictional failures with energies following a Gutenberg-Richter law. Moreover, foreshocks and aftershocks are described by Omori laws and interevent times also follow exactly the same distribution as real earthquakes, showing the existence of memory of past events.

Thermally activated crack fronts propagating in pinning disorder: simultaneous brittle/creep behaviour depending on scale.

We study theoretically the propagation of a crack front in mode I along an interface in a disordered elastic medium, with a numerical model considering a thermally activated rheology, toughness disorder and long-range elastic interactions. This model reproduces not only the large-scale dynamics of the crack front position in fast or creep loading regimes, but also the small-scale self-affine behaviour of the front. Two different scaling laws are predicted for the front morphology, with a Hurst exponent of 0.

Avalanches and extreme value statistics in interfacial crackling dynamics.

We study the avalanche and extreme statistics of the global velocity of a crack front, propagating slowly along a weak heterogeneous interface of a transparent polymethyl methacrylate block. The different loading conditions used (imposed constant velocity or creep relaxation) lead to a broad range of average crack front velocities. Our high-resolution and large dataset allows one to characterize in detail the observed intermittent crackling dynamics.

Emergency Department Computed Tomography Use for Non-traumatic Abdominal Pain: Minimal Variability.

Introduction: Variability in the use of computed tomography (CT) between providers in the emergency department (ED) suggests that CT is ordered on a provider rather than a patient level. We aimed to evaluate the variability of CT ordering practices for non-traumatic abdominal pain (NTAP) across physicians in the ED using patient-visit and physician-level factors.

Methods: We conducted a retrospective study among 6,409 ED visits for NTAP from January 1 to December 31, 2012, at a large, urban, academic, tertiary-care hospital.

Defens-IN! Human α-Defensin 5 Acts as an Unwitting Double Agent to Promote Shigella Infection.

Shigella pathogenesis has confounded researchers for years because of its narrow host selectivity and extraordinary infectious capability. In this issue of Immunity, Xu et al. (2018) identify a cunning mechanism whereby Shigella hijacks human α-defensin 5 to enhance its adhesion and subsequent invasion.