Perioperative care of a child with tetanus

Tetanus is caused by tetanospasmin, a toxin that is produced by the anaerobic bacterium, Clostridium tetani. Despite widespread vaccination, which limits its incidence in many parts of the world, tetanus may still occur owing to lack of immunisation related to religious tenets, cultural beliefs or inaccessibility to medical care. Of major concern during the perioperative care of such patients is control of the muscle spasms and the propensity for autonomic dysfunction, resulting in blood pressure instability. Ongoing muscle spasms may impair upper airway control or respiratory muscle function, thereby resulting in respiratory failure. Autonomic dysfunction may result in profound hypertension followed by hypotension, bradycardia and asystole. The pathophysiology of tetanus, its clinical manifestations, and current treatment options are discussed. The preoperative implications of tetanus and the care of these patients are reviewed.South Afr J Anaesth Analg, 2011;17(6):380-38

Percolation properties of the 2D Heisenberg model

We analyze the percolation properties of certain clusters defined on configurations of the 2--dimensional Heisenberg model. We find that, given any direction \vec{n} in O(3) space, the spins almost perpendicular to \vec{n} form a percolating cluster. This result gives indications of how the model can avoid a previously conjectured Kosterlitz-Thouless phase transition at finite temperature T.Comment: 4 pages, 3 eps figures. Revised version (more clear abstract, some new references

Sorption and fractionation of dissolved organic matter and associated phosphorus in agricultural soil

Molibility of dissolved organic matter (DOM) strongly affects the export of nitrogen (N) and phosphorus (P) from oils to surface waters. To study the sorption an mobility of dissolved organic C and P (DOC, DOP) in soil, the pH-dependent sorption of DOM to samples from Ap, EB, and Bt horizons from a Danish agircultural Humic Hapludult was investigated and a kinetic model applicable in field-scale model tested. Sorption experiments of 1 to 72 h duration were conducted at two pH levels (pH 5.0 and 7.0) and six initial DOC concentrtions (0-4.7 mmol L-1). Most sorption/desorption occurred during the first few hours. Dissolved organic carbon and DOP sorption decreased strongly with increased pH and desorption dominated at pH 7, especially for DOC. Due to fractionation during DOM sorption/desorption at DOC concentrations up to 2 mmol L-1, the solution fraction of DOM was enriched in P indicating preferred leaching of DOP. The kinetics of sorption was expressed as a function of how far the solution DOC or DOP concentrations deviate from "equilibrium". The model was able to simulate the kinetics of DOC and DOP sorption/desorption at all concentrations investigated and at both pH levels making it useful for incorporation in field-scale models for quantifying DOC and DOP dynamics

B-cell anergy: from transgenic models to naturally occurring anergic B cells?

Anergy, a condition in which cells persist in the periphery but are unresponsive to antigen, is responsible for silencing many self-reactive B cells. Loss of anergy is known to contribute to the development of autoimmune diseases, including systemic lupus erythematosus and type 1 diabetes. Multiple transgenic mouse models have enabled the dissection of mechanisms that underlie anergy, and recently, anergic B cells have been identified in the periphery of wild-type mice. Heterogeneity of mechanistic concepts developed using model systems has complicated our understanding of anergy and its biological features. In this Review, we compare and contrast the salient features of anergic B cells with a view to developing unifying mechanistic hypotheses that explain their lifestyles

Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.

A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. This causes a buildup of unengulfed cell debris. During mycobacterial infection, macrophages with lysosomal storage cannot migrate toward infected macrophages undergoing apoptosis in the tuberculous granuloma. The unengulfed apoptotic macrophages undergo secondary necrosis, causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal storage similarly impairs migration to newly infecting mycobacteria. This phenotype is recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of their alveolar macrophages exhibit lysosomal accumulations of tobacco smoke particulates and do not migrate to Mycobacterium tuberculosis. The incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis.This work was supported by the National Institutes of Health (R37AI054503, LR, R01NS082567, CBM, 5F30HL110455, RB, 1DP2-OD008614, DMT), the Wellcome Trust (LR), the National Institute of Health Research Cambridge Biomedical Research Centre (LR), the Health Research Board of Ireland (HRA_POR/2013/387, MO’S and CSA/2012/16, JK), and The Royal City of Dublin Hospital Trust (Grant 146, JK).This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.cell.2016.02.034

Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.

The blockade of phagolysosomal fusion is considered a critical mycobacterial strategy to survive in macrophages. However, viable mycobacteria have been observed in phagolysosomes during infection of cultured macrophages, and mycobacteria have the virulence determinant MarP, which confers acid resistance in vitro. Here we show in mice and zebrafish that innate macrophages overcome mycobacterial lysosomal avoidance strategies to rapidly deliver a substantial proportion of infecting bacteria to phagolysosomes. Exploiting the optical transparency of the zebrafish, we tracked the fates of individual mycobacteria delivered to phagosomes versus phagolysosomes and discovered that bacteria survive and grow in phagolysosomes, though growth is slower. MarP is required specifically for phagolysosomal survival, making it an important determinant for the establishment of mycobacterial infection in their hosts. Our work suggests that if pathogenic mycobacteria fail to prevent lysosomal trafficking, they tolerate the resulting acidic environment of the phagolysosome to establish infection.National Institutes of Health (Grant IDs: R37AI054503, R01 AI076327, 5T32HD007233, 5F30HL110455), Wellcome Trust, National Institute of Health Research Cambridge Biomedical Research CentreThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.chom.2016.07.00

Precision Prediction for the Big-Bang Abundance of Primordial Helium

Within the standard models of particle physics and cosmology we have calculated the big-bang prediction for the primordial abundance of \he to a theoretical uncertainty of less than 0.1 \pct $(\delta Y_P < \pm 0.0002)$, improving the current theoretical precision by a factor of 10. At this accuracy the uncertainty in the abundance is dominated by the experimental uncertainty in the neutron mean lifetime, $\tau_n = 885.4 \pm 2.0 sec$. The following physical effects were included in the calculation: the zero and finite-temperature radiative, Coulomb and finite-nucleon-mass corrections to the weak rates; order-$\alpha$ quantum-electrodynamic correction to the plasma density, electron mass, and neutrino temperature; and incomplete neutrino decoupling. New results for the finite-temperature radiative correction and the QED plasma correction were used. In addition, we wrote a new and independent nucleosynthesis code designed to control numerical errors to be less than 0.1\pct. Our predictions for the \EL[4]{He} abundance are presented in the form of an accurate fitting formula. Summarizing our work in one number, $Y_P(\eta = 5\times 10^{-10}) = 0.2462 \pm 0.0004 (expt) \pm < 0.0002 (theory)$. Further, the baryon density inferred from the Burles-Tytler determination of the primordial D abundance, $\Omega_B h^2 = 0.019\pm 0.001$, leads to the prediction: $Y_P = 0.2464 \pm 0.0005 (D/H) \pm < 0.0002 (theory) \pm 0.0005 (expt)$. This ``prediction'' and an accurate measurement of the primeval \he abundance will allow an important consistency test of primordial nucleosynthesis.Comment: Replaced fitting formulas - new versions differ by small but significant amount. Other minor changes. 30 pages, 17 figures, 5 table

Susceptibility and Percolation in 2D Random Field Ising Magnets

The ground state structure of the two-dimensional random field Ising magnet is studied using exact numerical calculations. First we show that the ferromagnetism, which exists for small system sizes, vanishes with a large excitation at a random field strength dependent length scale. This {\it break-up length scale} $L_b$ scales exponentially with the squared random field, $\exp(A/\Delta^2)$. By adding an external field $H$ we then study the susceptibility in the ground state. If $L>L_b$, domains melt continuously and the magnetization has a smooth behavior, independent of system size, and the susceptibility decays as $L^{-2}$. We define a random field strength dependent critical external field value $\pm H_c(\Delta)$, for the up and down spins to form a percolation type of spanning cluster. The percolation transition is in the standard short-range correlated percolation universality class. The mass of the spanning cluster increases with decreasing $\Delta$ and the critical external field approaches zero for vanishing random field strength, implying the critical field scaling (for Gaussian disorder) $H_c \sim (\Delta -\Delta_c)^\delta$, where $\Delta_c = 1.65 \pm 0.05$ and $\delta=2.05\pm 0.10$. Below $\Delta_c$ the systems should percolate even when H=0. This implies that even for H=0 above $L_b$ the domains can be fractal at low random fields, such that the largest domain spans the system at low random field strength values and its mass has the fractal dimension of standard percolation $D_f = 91/48$. The structure of the spanning clusters is studied by defining {\it red clusters}, in analogy to the ``red sites'' of ordinary site-percolation. The size of red clusters defines an extra length scale, independent of $L$.Comment: 17 pages, 28 figures, accepted for publication in Phys. Rev.

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Finite temperature effects on cosmological baryon diffusion and inhomogeneous Big-Bang nucleosynthesis

We have studied finite temperature corrections to the baryon transport cross sections and diffusion coefficients. These corrections are based upon the recently computed renormalized electron mass and the modified state density due to the background thermal bath in the early universe. It is found that the optimum nucleosynthesis yields computed using our diffusion coefficients shift to longer distance scales by a factor of about 3. We also find that the minimum value of $^4 He$ abundance decreases by $\Delta Y_p \simeq 0.01$ while $D$ and $^7 Li$ increase. Effects of these results on constraints from primordial nucleosynthesis are discussed. In particular, we find that a large baryonic contribution to the closure density (\Omega_b h_{50}^{2} \lsim 0.4) may be allowed in inhomogeneous models corrected for finite temperature.Comment: 7 pages, 6 figures, submitted to Phys. Rev.