A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

Protein toxins produced by bacteria are the cause of many life-threatening diarrheal diseases. Many of these toxins, including cholera toxin (CT), enter the cell by first binding to glycolipids in the cell membrane. Inhibiting these multivalent protein/carbohydrate interactions would prevent the toxin from entering cells and causing diarrhea. Here we demonstrate that the site-specific modification of a protein scaffold, which is perfectly matched in both size and valency to the target toxin, provides a convenient route to an effective multivalent inhibitor. The resulting pentavalent neoglycoprotein displays an inhibition potency (IC50) of 104 pM for the CT B-subunit (CTB), which is the most potent pentavalent inhibitor for this target reported thus far. Complexation of the inhibitor and CTB resulted in a protein heterodimer. This inhibition strategy can potentially be applied to many multivalent receptors and also opens up new possibilities for protein assembly strategies

Terms of international classification for Nursing Practice in motor and physical rehabilitation

OBJECTIVE To validate terms of nursing language especially for physical-motor rehabilitation and map them to the terms of ICNP® 2.0. METHOD A methodology research based on document analysis, with collection and analysis of terms from 1,425 records. RESULTS 825 terms were obtained after the methodological procedure, of which 226 had still not been included in the ICNP® 2.0. These terms were distributed as follows: 47 on the Focus axis; 15 on the Judgment axis; 31 on the Action axis; 25 on the Location axis; 102 on the Means axis; three on the Time axis; and three on the Client axis. All non-constant terms in ICNP® have been validated by experts, having reached an agreement index ≥0.80. CONCLUSION The ICNP® is applicable and used in nursing care for physical-motor rehabilitation

Evaluating a transfer gradient assumption in a fomite-mediated microbial transmission model using an experimental and Bayesian approach

Current microbial exposure models assume that microbial exchange follows a concentration gradient during hand-to-surface contacts. Our objectives were to evaluate this assumption using transfer efficiency experiments and to evaluate a model's ability to explain concentration changes using approximate Bayesian computation (ABC) on these experimental data. Experiments were conducted with two phages (MS2, ΦX174) simultaneously to study bidirectional transfer. Concentrations on the fingertip and surface were quantified before and after fingertip-to-surface contacts. Prior distributions for surface and fingertip swabbing efficiencies and transfer efficiency were used to estimate concentrations on the fingertip and surface post contact. To inform posterior distributions, Euclidean distances were calculated for predicted detectable concentrations (log10 PFU cm−2) on the fingertip and surface post contact in comparison with experimental values. To demonstrate the usefulness of posterior distributions in calibrated model applications, posterior transfer efficiencies were used to estimate rotavirus infection risks for a fingertip-to-surface and subsequent fingertip-to-mouth contact. Experimental findings supported the transfer gradient assumption. Through ABC, the model explained concentration changes more consistently when concentrations on the fingertip and surface were similar. Future studies evaluating microbial transfer should consider accounting for differing fingertip-to-surface and surface-to-fingertip transfer efficiencies and extend this work for other microbial types

Desynchronizing effect of high-frequency stimulation in a generic cortical network model

Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS) are two different applications of electrical current to the brain used in different areas of medicine. Both have a similar frequency dependence of their efficiency, with the most pronounced effects around 100Hz. We apply superthreshold electrical stimulation, specifically depolarizing DC current, interrupted at different frequencies, to a simple model of a population of cortical neurons which uses phenomenological descriptions of neurons by Izhikevich and synaptic connections on a similar level of sophistication. With this model, we are able to reproduce the optimal desynchronization around 100Hz, as well as to predict the full frequency dependence of the efficiency of desynchronization, and thereby to give a possible explanation for the action mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive Neurodynamic

Phlegmonous colitis: another source of sepsis in cirrhotic patients?

<p>Abstract</p> <p>Background</p> <p>The clinical relevance of phlegmonous colitis (PC), a rare autopsy finding in cirrhotic patients, is poorly documented. We postulated that PC might be a source of sepsis in patients with portal hypertensive colopathy (PHC).</p> <p>Case presentation</p> <p>We report three cirrhotic patients who were admitted with abdominal sepsis and who illustrate, to various degrees, the clinico-pathological sequence of colonic alterations associated with portal hypertension. Two cirrhotic patients with PHC developed gram-negative bacteraemia and quickly responded to intravenous antibiotics. Another cirrhotic patient underwent emergency colectomy for PC, and subsequently died from multiple organ failure. Histological alterations in the operative specimen included: a) mucosal ulcerations; b) disseminated micro-abscesses in the submucosa; and c) a severe vasculopathy leading to complete obliteration of submucosal blood vessels.</p> <p>Conclusions</p> <p>These data suggest that cirrhotic patients with PHC may progress towards PC, which, in turn, may be the cause for life-threatening sepsis.</p

Unusual Thermodynamics on the Fuzzy 2-Sphere

Higher spin Dirac operators on both the continuum sphere($S^2$) and its fuzzy analog($S^2_F$) come paired with anticommuting chirality operators. A consequence of this is seen in the fermion-like spectrum of these operators which is especially true even for the case of integer-spin Dirac operators. Motivated by this feature of the spectrum of a spin 1 Dirac operator on $S_F^2$, we assume the spin 1 particles obey Fermi-Dirac statistics. This choice is inspite of the lack of a well defined spin-statistics relation on a compact surface such as $S^2$. The specific heats are computed in the cases of the spin $\frac{1}{2}$ and spin 1 Dirac operators. Remarkably the specific heat for a system of spin $\frac{1}{2}$ particles is more than that of the spin 1 case, though the number of degrees of freedom is more in the case of spin 1 particles. The reason for this is inferred through a study of the spectrums of the Dirac operators in both the cases. The zero modes of the spin 1 Dirac operator is studied as a function of the cut-off angular momentum $L$ and is found to follow a simple power law. This number is such that the number of states with positive energy for the spin 1 and spin $\frac{1}{2}$ system become comparable. Remarks are made about the spectrums of higher spin Dirac operators as well through a study of their zero-modes and the variation of their spectrum with degeneracy. The mean energy as a function of temperature is studied in both the spin $\frac{1}{2}$ and spin 1 cases. They are found to deviate from the standard ideal gas law in 2+1 dimensions.Comment: 19 pages, 7 figures. The paper has been significantly modified. Main results are unchange