617 research outputs found

    Spin ice on the trillium lattice studied by Monte Carlo calculations

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    We study a local ferromagnetic Ising model for classical spins on the trillium lattice. The ground state of this model features two spins out(/in) and one spin in(/out) on each triangle, and leads to a macroscopic ground state degeneracy. Our Monte Carlo simulations find a ground state entropy intermediate to that of spin ice on the kagome and pyrochlore lattices, suggesting that trillium spin ice is highly frustrated. To motivate the search for trillium spin ice, we calculate the magnetic susceptibility and structure factor. We note the qualitative resemblance of the susceptibility to previously published work on EuPtSi, which features local moments on the trillium lattice.Comment: 8 pages, 6 figure

    Post-operative atrial fibrillation is influenced by beta-blocker therapy but not by pre-operative atrial cellular electrophysiology

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    We investigated whether post-cardiac surgery (CS) new-onset atrial fibrillation (AF) is predicted by pre-CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta-blocker therapy may involve pre-CS pharmacological remodeling. Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole-cell patch-clamp technique. Post-CS AF occurred in 53 of 212 patients (25%). Those with post-CS AF were older than those without (67 ± 2 vs 62 ± 1 years, P = 0.005). In cells from patients with post-CS AF, the action potential duration at 50% and 90% repolarization, maximum upstroke velocity, and effective refractory period (ERP) were 13 ± 4 ms, 217 ± 16 ms, 185 ± 10 V/s, and 216 ± 14 ms, respectively (n = 30 cells, 11 patients). Peak L-type Ca2+ current, transient outward and inward rectifier K+ currents, and the sustained outward current were −5.0 ± 0.5, 12.9 ± 2.4, −4.1 ± 0.4, and 9.7 ± 1.0 pA/pF, respectively (13-62 cells, 7-19 patients). None of these values were significantly different in cells from patients without post-CS AF (P > 0.05 for each, 60-279 cells, 29-86 patients), confirmed by multiple and logistic regression. In patients treated >7 days with a beta-blocker pre-CS, the incidence of post-CS AF was lower than in non-beta-blocked patients (13% vs 27%, P = 0.038). Pre-CS beta-blockade was associated with a prolonged pre-CS atrial cellular ERP (P = 0.001), by a similar degree (∼20%) in those with and without post-CS AF. Conclusion: Pre-CS human atrial cellular electrophysiology does not predict post-CS AF. Chronic beta-blocker therapy is associated with a reduced incidence of post-CS AF, unrelated to a pre-CS ERP-prolonging effect of this treatment

    Enteric helminths promote Salmonella co-infection by altering the intestinal metabolome

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    Intestinal helminth infections occur pre dominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional three-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial co-infection

    Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

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    Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

    Spectroscopy of 28^{28}Na: shell evolution toward the drip line

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    Excited states in 28^{28}Na have been studied using the β\beta-decay of implanted 28^{28}Ne ions at GANIL/LISE as well as the in-beam γ\gamma-ray spectroscopy at the NSCL/S800 facility. New states of positive (Jπ^{\pi}=3,4+^+) and negative (Jπ^{\pi}=1-5^-) parity are proposed. The former arise from the coupling between 0d_5/2\_{5/2} protons and a 0d_3/2\_{3/2} neutron, while the latter are due to couplings with 1p_3/2\_{3/2} or 0f_7/2\_{7/2} neutrons. While the relative energies between the Jπ^{\pi}=1-4+^+ states are well reproduced with the USDA interaction in the N=17 isotones, a progressive shift in the ground state binding energy (by about 500 keV) is observed between 26^{26}F and 30^{30}Al. This points to a possible change in the proton-neutron 0d_5/2\_{5/2}-0d_3/2\_{3/2} effective interaction when moving from stability to the drip line. The presence of Jπ^{\pi}=1-4^- negative parity states around 1.5 MeV as well as of a candidate for a Jπ^{\pi}=5^- state around 2.5 MeV give further support to the collapse of the N=20 gap and to the inversion between the 0f_7/2\_{7/2} and 1p_3/2\_{3/2} levels below Z=12. These features are discussed in the framework of Shell Model and EDF calculations, leading to predicted negative parity states in the low energy spectra of the 26^{26}F and 25^{25}O nuclei.Comment: Exp\'erience GANIL/LISE et NSCL/S80

    Association of Video Game Use With Body Mass Index and Other Energy-Balance Behaviors in Children

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    Importance Childhood obesity is one of the biggest public health threats facing the UK, and video game use is considered a risk behavior for obesity among children. However, few studies have explored the prospective association between video game use and body mass index (BMI) or the potential mediators of this association. Objectives To investigate whether a longer-term association exists between video game use at a young age and BMI SD score in later years, independent of television use, and to ascertain whether this association is mediated by other energy-balance behaviors. Design, Setting, and Participants This cohort study is a secondary analysis of data from the Millennium Cohort Study, a nationally representative sample of children who were born in the UK between September 1, 2000, and January 31, 2002, that focused on data collected when the children were aged 5, 7, 11, and 14 years. Data for all variables, except BMI, were provided by parental or caregiver reporting if the children were younger than 14 years of age. At age 14 years, the children self-reported their own behavior. Initial data analysis was conducted between September 18, 2018, and September 28, 2018, with supplementary analyses conducted from October 7, 2019, to November 22, 2019. Main Outcomes and Measures The main outcome variable was BMI SD scores, with video game use as the exposure variable of interest. Physical activity, bedtime regularity, sugar-sweetened beverage consumption, and high-calorie food consumption were included as potential mediating behaviors. Results The full sample comprised 16 376 children and had a nearly equal number of boys (8393 [51.3%]) and girls (7983 [48.7%]). Every 1 SD increase in the number of hours of video game use at age 5 years was associated with a β = 0.018 higher BMI SD score at age 14 years (95% CI, 0.004-0.032). A small partial mediation of this association was found (direct association: β = 0.017 [95% CI, 0.003-0.031]; indirect association: β = 0.0011 [95% CI, 0.0003-0.0019]), suggesting that irregular bedtimes and higher consumption of sugar-sweetened beverages were mediators. The mediation model accounted for 36.7% (95% CI, 35.5-37.8) of the variance of the BMI SD score at age 14 years. Conclusions and Relevance Results of this study suggest a small (and not clinically meaningful) association between video game use in early childhood and higher BMI in later years, which may be mediated by irregular bedtimes and higher consumption of sugar-sweetened beverages. Future interventions to prevent childhood obesity should incorporate health promotion in mainstream video games to target children most at risk because of their high level of video game use

    Th2 Cell-Intrinsic Hypo-Responsiveness Determines Susceptibility to Helminth Infection

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    The suppression of protective Type 2 immunity is a principal factor driving the chronicity of helminth infections, and has been attributed to a range of Th2 cell-extrinsic immune-regulators. However, the intrinsic fate of parasite-specific Th2 cells within a chronic immune down-regulatory environment, and the resultant impact such fate changes may have on host resistance is unknown. We used IL-4gfp reporter mice to demonstrate that during chronic helminth infection with the filarial nematode Litomosoides sigmodontis, CD4(+) Th2 cells are conditioned towards an intrinsically hypo-responsive phenotype, characterised by a loss of functional ability to proliferate and produce the cytokines IL-4, IL-5 and IL-2. Th2 cell hypo-responsiveness was a key element determining susceptibility to L. sigmodontis infection, and could be reversed in vivo by blockade of PD-1 resulting in long-term recovery of Th2 cell functional quality and enhanced resistance. Contrasting with T cell dysfunction in Type 1 settings, the control of Th2 cell hypo-responsiveness by PD-1 was mediated through PD-L2, and not PD-L1. Thus, intrinsic changes in Th2 cell quality leading to a functionally hypo-responsive phenotype play a key role in determining susceptibility to filarial infection, and the therapeutic manipulation of Th2 cell-intrinsic quality provides a potential avenue for promoting resistance to helminths
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