Vagal Stimulation Modulates Inflammation through a Ghrelin Mediated Mechanism in Traumatic Brain Injury

Traumatic brain injury (TBI) releases a cascade of inflammatory cytokines. Vagal nerve stimulation (VNS) and ghrelin have known anti-inflammatory effects; furthermore, ghrelin release is stimulated by acetylcholine. We hypothesized VNS decreases post-TBI inflammation through a ghrelin-mediated mechanism. TBI was created in five groups of mice: sham, TBI, TBI/ghrelin, TBI/VNS, and TBI/VNS/ghrelin receptor antagonist (GRa). Serum and tissue ghrelin, and serum TNF-α were measured. Ghrelin increased following VNS 2 h post-TBI compared to sham or TBI. At 6 h, TBI and TBI/VNS/GRa had increased TNF-α compared to sham while TBI/VNS and TBI/ghrelin had TNF-α level comparable to sham. The highest ghrelin was measured in stomach where TBI decreased ghrelin in contrast to an increase by VNS. In conclusion, VNS increased serum ghrelin and decreased TNF-α following TBI. This was abrogated with GRa. Our data suggests that ghrelin plays an important role in the anti-inflammatory effects of VNS following TBI

EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease

Shifting the Burden of Corporate Taxes Heterogeneity in Direct Wage Incidence

We contribute to the empirical literature on the effective incidence of corporate income taxation. We focus on the so-called direct incidence via the wage bargaining process. Building on the innovative framework of Arulampalam, Devereux and Maffini (2012), we analyze the importance of various dimensions of heterogeneity at the firm-level. In particular, we investigate the distinct effects of (i) firm size, (ii) level of profitability, and (iii) competition intensity across (iv) different economic sectors. Furthermore, we investigate the relative importance of the surrounding institutional setting. To this end, a firm-level within-country approach is pursued separately for two different economies, namely France and the United Kingdom, which can be regarded as polar cases with respect to the relevant features of the wage-setting process. However, in many respects, we find surprisingly similar results for both countries. Thereby, this paper also adds to the literature by providing new insights on the degree to which results from previous single-country studies can possibly be generalized.Die effektive Inzidenz der Körperschaftsteuer ist ein theoretisch wie empirisch kontroverses Thema. Das Paper leistet einen Beitrag zur empirischen Literatur und fokussiert dabei auf die sogenannte direkte Inzidenz über den Lohnverhandlungskanal. Aufbauend auf dem innovativen Ansatz von Arulampalam, Devereux und Maffini (2012) wird die Bedeutung von verschiedenen Dimensionen der Heterogenität auf der Firmenebene analysiert. Konkret wird erforscht, welchen Einfluss (i) Firmengröße, (ii) Profitabilität und (iii) Wettbewerbsintensität in (iv) verschiedenen Branchen auf das Ausmaß ausüben, in dem die Last der Körperschaftsteuer auf die Löhne der Beschäftigten überwälzt wird. Darüber hinaus wird untersucht, welche Relevanz dabei den institutionellen Gegebenheiten der Lohnverhandlungen zukommt. Dazu werden alle Analysen separat für Frankreich und das Vereinigte Königreich vollzogen, deren Volkswirtschaften mit Blick auf Arbeitsmarktinstitutionen als polare Fälle gelten können. Die jeweiligen Ergebnisse für die beiden Länder sind sich jedoch qualitativ wie quantitativ überraschend ähnlich. Insofern gibt die Studie auch einen Hinweis darauf, inwiefern die Ergebnisse aus auf einzelne Länder bezogene Studien zur effektiven Lohninzidenz der Körperschaftsteuer generalisiert werden können

The Cytoplasmic Tail of Glycoprotein M (gpUL100) Expresses Trafficking Signals Required for Human Cytomegalovirus Assembly and Replication▿

The virion envelope of human cytomegalovirus (HCMV) is complex and consists of an incompletely defined number of glycoproteins. The gM/gN protein complex is the most abundant protein component of the envelope. Studies have indicated that deletion of the viral gene encoding either gM or gN is a lethal mutation. Analysis of the amino acid sequence of gM disclosed a C-terminal acidic cluster of amino acids and a tyrosine-containing trafficking motif, both of which are well-described trafficking/sorting signals in the cellular secretory pathway. To investigate the roles of these signals in the trafficking of the gM/gN complex during virus assembly, we made a series of gM (UL100 open reading frame) mutants in the AD169 strain of HCMV. Mutant viruses that lacked the entire C-terminal cytoplasmic tail of gM were not viable, suggesting that the cytoplasmic tail of gM is essential for virus replication. In addition, the gM mutant protein lacking the cytoplasmic domain exhibited decreased protein stability. Mutant viruses with a deletion of the acidic cluster or alanine substitutions in tyrosine-based motifs were viable but exhibited a replication-impaired phenotype suggestive of a defect in virion assembly. Analysis of these mutant gMs using static immunofluorescence and fluorescence recovery after photobleaching demonstrated delayed kinetics of intracellular localization of the gM/gN protein to the virus assembly compartment compared to the wild-type protein. These data suggest an important role of the glycoprotein gM during virus assembly, particularly in the dynamics of gM trafficking during viral-particle assembly

Clinical Teaching: An Evidence-based Guide to Best Practices from the Council of Emergency Medicine Residency Directors

Clinical teaching is the primary educational tool use to train learners from day one of medical school all the way to the completion of fellowship. However, concerns over time constraints and patient census have led to a decline in bedside teaching. This paper provides a critical review of the literature on clinical teaching with a focus on instructor teaching strategies, clinical teaching models, and suggestions for incorporating technology. Recommendations for instructor-related teaching factors include adequate preparation, awareness of effective teacher attributes, using evidence-based-knowledge dissemination strategies, ensuring good communication, and consideration of environmental factors. Proposed recommendations for potential teaching strategies include the Socratic method, the One-Minute Preceptor model, SNAPPS, ED STAT, teaching scripts, and bedside presentation rounds. Additionally, this article will suggest approaches to incorporating technology into clinical teaching, including just-in-time training, simulation, and telemedical teaching. This paper provides readers with strategies and techniques for improving clinical teaching effectiveness

Clinical Teaching: An Evidence-based Guide to Best Practices from the Council of Emergency Medicine Residency Directors

Clinical teaching is the primary educational tool use to train learners from day one of medical school all the way to the completion of fellowship. However, concerns over time constraints and patient census have led to a decline in bedside teaching. This paper provides a critical review of the literature on clinical teaching with a focus on instructor teaching strategies, clinical teaching models, and suggestions for incorporating technology. Recommendations for instructor-related teaching factors include adequate preparation, awareness of effective teacher attributes, using evidence-based-knowledge dissemination strategies, ensuring good communication, and consideration of environmental factors. Proposed recommendations for potential teaching strategies include the Socratic method, the One-Minute Preceptor model, SNAPPS, ED STAT, teaching scripts, and bedside presentation rounds. Additionally, this article will suggest approaches to incorporating technology into clinical teaching, including just-in-time training, simulation, and telemedical teaching. This paper provides readers with strategies and techniques for improving clinical teaching effectiveness

Solid-State Characterization and Relative Formation Enthalpies To Evaluate Stability of Cocrystals of an Antidiabetic Drug

The current study integrates formation enthalpy and traditional slurry experiments to quickly assess the physical stability of cocrystal drug substance candidates for their potential to support drug development. Cocrystals of an antidiabetic drug (GKA) with nicotinamide (NMA), vanillic acid (VLA), and ethyl vanillin (EVL) were prepared and characterized by powder X-ray diffractometry (PXRD), spectroscopic, and thermal techniques. The formation enthalpies of the cocrystals, and their physical mixtures (GKA + coformer) were measured by the differential scanning calorimetry (DSC) method reported by Zhang et al. [Cryst. Growth Des. 2012, 12 (8), 4090−4097]. The experimentally measured differences in the relative formation enthalpies obtained by integrating the heat flow of each cocrystal against the respective physical mixture were correlated to the physical stability of the cocrystals in the solid state. The relative formation enthalpies of all of the cocrystals studied suggest that the cocrystals are not physically stable at room temperature versus their physical mixtures. To further address relative stability, the cocrystals were slurried in 30% v/v aqueous ethanol, and it was observed that all of the cocrystals revert to GKA within 48 h at room temperature. The slurry experiments are consistent with the relative instability of the cocrystals with respect to their physical mixtures suggested by the DSC results