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Key Clinical Message Patients mimicking appendicitis symptoms in a rural setting or those post‐appendectomy, indicating cecal volvulus, should always be considered. Swift action can prevent catastrophic consequences. Abstract We present a case of a 14‐year‐old female who initially underwent open appendectomy for acute appendicitis and subsequently experienced symptoms of abdominal distention, vomiting, and fever. Her condition deteriorated following the appendectomy, despite a prior appendectomy for similar symptoms at a different facility. A computed tomography (CT) scan identified cecal volvulus as the underlying issue. This led to the performance of a laparotomy, cecopexy, and decompressive ileostomy. After six weeks, ileostomy closure was successfully carried out, and the patient currently enjoys good health. This case highlights the significance of considering uncommon factors as potential contributors to postoperative complications in young patients.

The central Slave Geological Province is situated 450–650 km from the presumed spreading centre of the Keewatin Dome of the Laurentide Ice Sheet, and it differs from the western Canadian Arctic, where recent thaw-induced landscape changes in Laurentide ice-marginal environments are already abundant. Although much of the terrain in the central Slave Geological Province is mapped as predominantly bedrock and ice-poor, glacial deposits of varying thickness occupy significant portions of the landscape in some areas, creating a mosaic of permafrost conditions. Limited evidence of ice-rich ground, a key determinant of thaw-induced landscape change, exists. Carbon and soluble cation contents in permafrost are largely unknown in the area. Twenty-four boreholes with depths up to 10 m were drilled in tundra north of Lac de Gras to address these regional gaps in knowledge and to better inform projections and generalizations at a coarser scale. Excess-ice contents of 20 %–60 %, likely remnant Laurentide basal ice, are found in upland till, suggesting that thaw subsidence of metres to more than 10 m is possible if permafrost were to thaw completely. Beneath organic terrain and in fluvially reworked sediment, aggradational ice is found. The variability in abundance of ground ice poses long-term challenges for engineering, and it makes the area susceptible to thaw-induced landscape change and mobilization of sediment, solutes and carbon several metres deep. The nature and spatial patterns of landscape changes, however, are expected to differ from ice-marginal landscapes of western Arctic Canada, for example, based on greater spatial and stratigraphic heterogeneity. Mean organic-carbon densities in the top 3 m of soil profiles near Lac de Gras are about half of those reported in circumpolar statistics; deeper deposits have densities ranging from 1.3–10.1 kg C m−3, representing a significant additional carbon pool. The concentration of total soluble cations in mineral soils is lower than at previously studied locations in the western Canadian Arctic. This study can inform permafrost investigations in other parts of the Slave Geological Province, and its data can support scenario simulations of future trajectories of permafrost thaw. Preserved Laurentide basal ice can support new ways of studying processes and phenomena at the base of an ice sheet.

We report on a precise measurement of double-polarization asymmetries in electron-induced breakup of He3 proceeding to pd and ppn final states, performed in quasi-elastic kinematics at Q2=0.25(GeV/c)2 for missing momenta up to 250MeV/c. These observables represent highly sensitive tools to investigate the electromagnetic and spin structure of He3 and the relative importance of two- and three-body effects involved in the breakup reaction dynamics. The measured asymmetries cannot be satisfactorily reproduced by state-of-the-art calculations of He3 unless their three-body segment is adjusted, indicating that the spin-dependent part of the nuclear interaction governing the three-body breakup process is much smaller than previously thought. Keywords: Double-polarization asymmetry, Helium-3 nucleus, Proton knock-out

The spin-structure functions g1 and g2, and the spin-dependent partial cross-section σTT have been extracted from the polarized cross-sections differences, Δσ∥(ν,Q2) and Δσ⊥(ν,Q2) measured for the He3→(e→,e′)X reaction, in the E97-110 experiment at Jefferson Lab. Polarized electrons with energies from 1.147 to 4.404 GeV were scattered at angles of 6∘ and 9∘ from a longitudinally or transversely polarized 3He target. The data cover the kinematic regions of the quasi-elastic, resonance production and beyond. From the extracted spin-structure functions, the first moments Γ1‾(Q2), Γ2(Q2) and ITT(Q2) are evaluated with high precision for the neutron in the Q2 range from 0.035 to 0.24GeV2. The comparison of the data and the chiral effective field theory predictions reveals the importance of proper treatment of the Δ degree of freedom for spin observables.

Corynebacterium ulcerans is an important zoonotic pathogen which is causing diphtheria-like disease in humans globally. In this study, the genomes of three recently isolated C. ulcerans strains, 4940, 2590 and BR-AD 2649, respectively from an asymptomatic carrier, a patient with pharyngitis and a canine host, were sequenced to investigate their virulence potential. A comparative analysis was performed including the published genome sequences of 16 other C. ulcerans isolates. C. ulcerans strains belong to two lineages; 13 strains are grouped together in lineage 1, and six strains comprise lineage 2. Consistent with the zoonotic nature of C. ulcerans infections, isolates from both the human and canine hosts clustered in both the lineages. Most of the strains possessed spaDEF and spaBC gene clusters along with the virulence genes cpp, pld, cwlH, nanH, rpfI, tspA and vsp1. The gene encoding Shiga-like toxin was only present in one strain, and 11 strains carried the tox gene encoding the diphtheria-like toxin. However, none of strains 4940, 2590 and BR-AD 2649 carried any toxin genes. These strains varied in the number of prophages in their genomes, which suggests that they play an important role in introducing diversity in C. ulcerans. The pan-genomic analyses revealed a variation in the number of membrane-associated and secreted proteins that may contribute to the variation in pathogenicity among different strains. Keywords: Corynebacterium ulcerans, diphtheria, nontoxigenic, sore throat, toxigenic, vaccine, virulence, zoonotic

Due to the lack of free neutron targets, studies of the structure of the neutron are typically made by scattering electrons from either 2H or 3He targets. In order to extract useful neutron information from a 3He target, one must understand how the neutron in a 3He system differs from a free neutron by taking into account nuclear effects such as final state interactions and meson exchange currents. The target single spin asymmetry Ay0 is an ideal probe of such effects, as any deviation from zero indicates effects beyond plane wave impulse approximation. New measurements of the target single spin asymmetry Ay0 at Q2 of 0.46 and 0.96 (GeV/c)2 were made at Jefferson Lab using the quasi-elastic He↑3(e,e′n) reaction. Our measured asymmetry decreases rapidly, from >20% at Q2=0.46 (GeV/c)2 to nearly zero at Q2=0.96 (GeV/c)2, demonstrating the fall-off of the reaction mechanism effects as Q2 increases. We also observed a small ϵ-dependent increase in Ay0 compared to previous measurements, particularly at moderate Q2. This indicates that upcoming high Q2 measurements from the Jefferson Lab 12 GeV program can cleanly probe neutron structure from polarized 3He using plane wave impulse approximation. Keywords: Neutron, Quasi-elastic, Polarized, 3He, Electron scattering, Single spin asymmetry

It remains a challenge to find the structure and the distribution of the constituents of nucleons. Here the authors use a scattering method to get information about the gluons and quarks inside a proton and separate the contribution of Bethe-Heitler from the deeply virtual Compton scattering process.

We report on new p(e,e′p)π∘ measurements at the Δ+(1232) resonance at the low momentum transfer region, where the mesonic cloud dynamics is predicted to be dominant and rapidly changing, offering a test bed for chiral effective field theory calculations. The new data explore the Q2 dependence of the resonant quadrupole amplitudes and for the first time indicate that the Electric and the Coulomb quadrupole amplitudes converge as Q2→0. The measurements of the Coulomb quadrupole amplitude have been extended to the lowest momentum transfer ever reached, and suggest that more than half of its magnitude is attributed to the mesonic cloud in this region. The new data disagree with predictions of constituent quark models and are in reasonable agreement with dynamical calculations that include pion cloud effects, chiral effective field theory and lattice calculations. The measurements indicate that improvement is required to the theoretical calculations and provide valuable input that will allow their refinements.

We have performed precision measurements of the double-spin virtual-photon asymmetry A1 on the neutron in the deep inelastic scattering regime, using an open-geometry, large-acceptance spectrometer and a longitudinally and transversely polarized 3He target. Our data cover a wide kinematic range 0.277≤x≤0.548 at an average Q2 value of 3.078 (GeV/c)2, doubling the available high-precision neutron data in this x range. We have combined our results with world data on proton targets to make a leading-order extraction of the ratio of polarized-to-unpolarized parton distribution functions for up quarks and for down quarks in the same kinematic range. Our data are consistent with a previous observation of an A1n zero crossing near x=0.5. We find no evidence of a transition to a positive slope in (Δd+Δd¯)/(d+d¯) up to x=0.548. Keywords: Spin structure functions, Nucleon structure, Parton distribution functions, Polarized electron scattering

Spontaneously contracting syncytia of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) are a useful model of human cardiac physiology and pharmacology. Various methods have been proposed to record this spontaneous activity and to evaluate drug effects, but many of these methods suffer from limited throughput and/or physiological relevance. We developed a high-throughput screening system to quantify the effects of exogenous compounds on hiPSC-CM's beating frequency, using a Ca-sensitive fluorescent dye and a temperature-controlled imaging multi-well plate reader. We describe how to prepare the cell plates and the compound plates and how to run the automated assay to achieve high sensitivity and reproducibility. We also describe how to transform and analyze the fluorescence data to provide reliable measures of drug effects on spontaneous rhythm. This assay can be used in drug discovery programs to guide chemical optimization away from, or toward, compounds affecting human cardiac function.

Under pathological conditions, the purinergic P2X7 receptor is activated by elevated concentrations of extracellular ATP. Thereby, the receptor forms a slowly dilating pore, allowing cations and, upon prolonged stimulation, large molecules to enter the cell. This process has a strong impact on cell signaling, metabolism, and viability. This study aimed to establish a link between gradual P2X7 activation and pharmacological endpoints including oxidative stress, hydrogen peroxide generation, and cytotoxicity. Mechanisms of cellular stress and cytotoxicity were studied in P2X7-transfected HEK293 cells. We performed real-time monitoring of metabolic and respiratory activity of cells expressing the P2X7-receptor protein using a cytosensor system. Agonistic effects were monitored using exogenously applied ATP or the stable analogue BzATP. Oxidative stress induced by ATP or BzATP in target cells was monitored by hydrogen peroxide release in human mononuclear blood cells. P2X7-receptor activation was studied by patch-clamp experiments using a primary mouse microglia cell line. Stimulation of the P2X7 receptor leads to ion influx, metabolic activation of target cells, and ultimately cytotoxicity. Conversion of the P2X7 receptor from a small cation channel to a large pore occurring under prolonged stimulation can be monitored in real time covering a time frame of milliseconds to hours. Selectivity of the effects can be demonstrated using the selective P2X7-receptor antagonist AZD9056. Our findings established a direct link between P2X7-receptor activation by extracellular ATP or BzATP and cellular events culminating in cytotoxicity. Mechanisms of toxicity include metabolic and oxidative stress, increase in intracellular calcium concentration and disturbance of mitochondrial membrane potential. Mitochondrial toxicity is suggested to be a key event leading to cell death.

Novel antibacterial drugs that are effective against infections caused by multidrug resistant pathogens are urgently needed. In a previous report, we have shown that tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. During the course of our optimization program, lead compound 5 was deprioritized due to adverse findings in cardiovascular safety studies. In the effort of mitigating these findings and optimizing further the pharmacological profile of this class of compounds, we have identified a subseries of tetrahydropyran-based molecules that are potent DNA gyrase and topoisomerase IV inhibitors and display excellent antibacterial activity against Gram positive pathogens, including clinically relevant resistant isolates. One representative of this class, compound 32d, elicited only weak inhibition of hERG K(+) channels and hNaV1.5 Na(+) channels, and no effects were observed on cardiovascular parameters in anesthetized guinea pigs. In vivo efficacy in animal infection models has been demonstrated against Staphylococcus aureus and Streptococcus pneumoniae strains.

The proteinVirB8 plays a critical role in the assembly and function of the Agrobacterium tumefaciens virB type IV secretion system (T4SS). The structure of the periplasmic domain of both A. tumefaciens and Brucella suis VirB8 has been determined, and site-directed mutagenesis has revealed amino acids involved in the dimerization of VirB8 and interactions with VirB4 and VirB10. We have shown previously that TraJ, the VirB8 homologue from pSB102, and the chimeric protein TraJB8, encompassing the cytoplasmic and transmembrane (TM) domains of TraJ and the periplasmic domain of VirB8, were unable to complement a B. suis mutant containing an in-frame deletion of the virB8 gene. This suggested that the presence of the TraJ cytoplasmic and TM domains could block VirB8 dimerization or assembly in the inner membrane. By bacterial two-hybrid analysis, we found that VirB8, TraJ, and the chimeras can all interact to form both homo- and heterodimers. However, the presence of the TM domain of TraJ resulted in much stronger interactions in both the homo- and heterodimers. We expressed the wild-type and chimeric proteins in wild-type B. suis. The presence of proteins carrying the TM domain of TraJ had a dominant negative effect, leading to complete loss of virulence. This suggests that the T4SS is a dynamic structure and that strong interactions block the spatial flexibility required for correct assembly and function.