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The cardiac muscarinic receptor (M2R) regulates heart rate, in part, by modulating the ace-tylcholine (ACh) activated K⁺ current I$_{K,ACh}$ through dissociation of G-proteins, that in turn activate K$_{ ACh}$ channels. Recently, M2Rs were noted to exhibit intrinsic voltage sensitivity, i.e. their affinity for ligands varies in a voltage dependent manner. The voltage sensitivity of M2R implies that the affinity for Ach (and thus the Ach effect) varies throughout the time course of a cardiac electrical cycle. The aim of this study was to investigate the contribution of M2R voltage sensitivity to the rate and shape of the human sinus node action potentials in physiological and pathophysiological conditions. We developed a Markovian model of the I$_{K,ACh}$ modulation by voltage and integrated it into a computational model of human sinus node. We performed simulations with the integrated model varying Ach concentration and voltage sensitivity. Low Ach exerted a larger effect on I$_{K,ACh}$ at hyperpolarized versus depolarized membrane voltages. This led to a slowing of the pacemaker rate due to an attenuated slope of phase 4 depolarization with only marginal effect on action potential duration and amplitude. We also simulated the theoretical effects of genetic variants that alter the voltage sensitivity of M2R. Modest negative shifts in voltage sensitivity, predicted to increase the affinity of the receptor for ACh, slowed the rate of phase 4 depolarization and slowed heart rate, while modest positive shifts increased heart rate. These simulations support our hypothesis that altered M2R voltage sensitivity contributes to disease and provide a novel mechanistic foundation to study clinical disorders such as atrial fibrillation and inappropriate sinus tachycardia.

Blastic plasmacytoid dendritic cell tumor is a rare, highly aggressive systemic neoplasm for which effective therapies have not yet been established. We describe a 73-year-old man with multiple nodules and patches emerging on the trunk and limbs. Lesional skin biopsy revealed a plasmacytoid dendritic cell tumor with dense dermal infiltrate of tumor cells with blastoid features. No apparent systemic involvement was identified in the initial stage. The patient was treated with prednisone daily, with notorious improvement of the skin lesions, although no complete remission was obtained. During the six-month follow-up period, no disease progression was documented, but fatal systemic progression occurred after that period of time.

Die Untersuchung von Entzündungsprofilen in der Nasenschleimhaut bei Rhinosinusitis erlaubt eine Phänotypisierung der Entzündungsreaktion und dem damit assoziierten klinischen Befunden. Eine entscheidende Bedeutung bei der Entzündungsreaktion kommt dem Inflammasom zu, welcher als[for full text, please go to the a.m. URL], 83. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie

This dissertation presents a comprehensive description of Xinka based on the missionary grammar "Arte de la lengua szinca" that was written by the priest Manuel Maldonado de Matos around 1773. Xinka is an isolate family of today mostly extinct, closely related languages in southeastern Guatemala. The "Arte de la lengua szinca" is the earliest source on Xinka grammar that is otherwise not well documented or described. The analysis of the late colonial grammar draws on comparative data, including (a) primary data that were documented by the author with the last Xinka-speakers in Guazacapán, Santa Rosa, Guatemala between 2000-03, and (b) further secondary linguistic data of Xinkan languages from the towns of Guazacapán, Chiquimulilla, Yupiltepeque, Jumaytepeque, Sinacantán and Jutiapa. The text addresses the methodological implications of describing colonial Xinka grammar based on such a heterogeneous corpus of diachronic and regionally diverse data. Besides the linguistic description, the dissertation contains information about the cultural context of the language as well as about the colonial document and the corpus of linguistic data. The appendix includes a concordance of the linguistic data from the colonial grammar and a dictionary of the lexical entries.

Hintergrund: Das Susac Syndrom ist eine die mikrovaskuläre Gefäßstruktur des Gehirns, der Retina und des Innenohres betreffende Endotheliopathie, die durch Senkung des Blutflusses und des Sauerstoffpartialdrucks eine ischämische Affektion bewirkt. Die in der Regel zeitlich verzögert[for full text, please go to the a.m. URL], 94. Jahrestagung der Vereinigung Südwestdeutscher Hals-Nasen-Ohrenärzte

Der Einfluss von Staphylokokken bei der chronischen Rhinosinusitis ist nicht gut untersucht. Grundsätzlich werden drei verschiedene Formen der Schleimhaut-Staphylokokken Interaktion unterschieden: intrazelluläre Persistenz, Infektion und Besiedlung. Der erste Schritt des Staphylokokken-Schleimaut[for full text, please go to the a.m. URL], 80. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie