Novel peptide calcitonin gene-related peptide antagonists for migraine therapy.

Objectives: It has previously been shown that the peptide (34Pro,35Phe)CGRP27-37 is a potent calcitonin gene-related peptide, CGRP receptor antagonist, and in this project we aimed to improve the antagonist potency through the structural modification of truncated C-terminal CGRP peptides.

Methods: Six peptide analogues were synthesized and the anti-CGRP activity confirmed using both in vitro and in vivo studies.

Key Findings: A 10 amino acid-containing peptide VPTDVGPFAF-NH2 (P006) was identified as a key candidate to take forward for in vivo evaluation, where it was shown to be an effective antagonist after intraperitoneal injection into mice.

Probing Peptidylprolyl Bond cis/trans Status Using Distal F NMR Reporters.

A method for measuring peptidylprolyl bond cis-trans conformational status in peptide models is described, using 4-fluorophenylalanine (4FPhe) as a distal reporter for F NMR. The %cis-Pro population was measured for peptides of the general structure Ac-X-Pro-Z-Ala-Ala-4FPhe (X and Z are proteinogenic amino acids) at pH 7.4, and provided conformational populations consistent with literature values obtained by more complex methods.

A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine.

Objectives: To investigate the formulation of the peptide-based antagonist ( Pro, Phe)CGRP , of the human calcitonin gene-related peptide (CGRP) receptor as a potential nasally delivered migraine treatment.

Methods: Peptide sequences were prepared using automated methods and purified by preparative HPLC. Their structure and stability were determined by LC-MS.

Design and development of stapled transmembrane peptides that disrupt the activity of G-protein-coupled receptor oligomers.

Membrane proteins can associate into larger complexes. Examples include receptor tyrosine complexes, ion channels, transporters, and G protein-coupled receptors (GPCRs). For the latter, there is abundant evidence indicating that GPCRs assemble into complexes, through both homo- and heterodimerization.

Fluorinated Prolines as Conformational Tools and Reporters for Peptide and Protein Chemistry.

Amide bonds at the proline nitrogen are particularly susceptible to rotation, affording cis and trans isomers. Installation of a stereochemically defined electron-withdrawing fluorine atom or fluorinated groups has the power to influence the cis- trans conformational preferences of the amide bond in X-(F)Pro (where X = any other amino acid). Advantageously, this also provides a sensitive reporter for F nuclear magnetic resonance (NMR) studies of protein conformation, interactions, and dynamics.

Disorder in convergent floral nanostructures enhances signalling to bees.

Diverse forms of nanoscale architecture generate structural colour and perform signalling functions within and between species. Structural colour is the result of the interference of light from approximately regular periodic structures; some structural disorder is, however, inevitable in biological organisms. Is this disorder functional and subject to evolutionary selection, or is it simply an unavoidable outcome of biological developmental processes? Here we show that disordered nanostructures enable flowers to produce visual signals that are salient to bees.

Death in the Digital Age: A Systematic Review of Information and Communication Technologies in End-of-Life Care.

Background: End-of-life (EOL) communication plays a critical role in ensuring that patients receive care concordant with their wishes and experience high quality of life. As the baby boomer population ages, scalable models of end-of-life communication will be needed to ensure that patients receive appropriate care. Information and communication technologies (ICTs) may help address the needs of this generation; however, few resources exist to guide the use of ICTs in EOL care.

Laryngeal mask placement in a teaching institution: analysis of difficult placements.

Background: Laryngeal mask airway (LMA) placement is now considered a common airway management practice. Although there are many studies which focus on various airway techniques, research regarding difficult LMA placement is limited, particularly for anesthesiologist trainees. In our retrospective analysis we tried to identify predictive factors of difficult LMA placement in an academic training program.

Predictive factors for difficult mask ventilation in the obese surgical population.

Background Difficult Mask Ventilation (DMV), is a situation in which it is impossible for an unassisted anesthesiologist to maintain oxygen saturation >90% using 100% oxygen and positive pressure ventilation to prevent or reverse signs of inadequate ventilation during mask ventilation.  The incidence varies from 0.08 - 15%.

Difficult mask ventilation in general surgical population: observation of risk factors and predictors.

Background: There are few predictors of difficult mask ventilation and a simple, objective, predictive system to identify patients at risk of difficult mask ventilation does not currently exist. We present a retrospective - subgroup analysis aimed at identifying predictive factors for difficult mask ventilation (DMV) in patients undergoing pre-operative airway assessment before elective surgery at a major teaching hospital.

Methods: Data for this retrospective analysis were derived from a database of airway assessments, management plans, and outcomes that were collected prospectively from August 2008 to May 2010 at a Level 1 academic trauma center.

Recent trends in airway management: we are not ready to give up fiberoptic endoscopy.

The purpose of this correspondence is to discuss recent findings related to current trends in airway management and to discuss the utilization rates of video laryngoscopes versus traditional techniques in USA, UK, and Canada. To highlight the increased use of video laryngoscopes in difficult airway situations, data on the use of alternative airway devices at our institution collected from 2008 to 2010 are presented alongside the results of previously published surveys collected from 2002 to 2013.

Anticipation of the difficult airway: preoperative airway assessment, an educational and quality improvement tool.

Background: Assessment of the potentially difficult airway (DA) is a critical aspect of resident education. We investigated the impact of a new assessment form on airway prediction and management by anaesthesia residents. We hypothesized that residents would demonstrate improvement in evaluation of DAs over the study duration.

Rapid laboratory detection of meningococcal disease outbreaks caused by serogroup C Neisseria meningitidis.

Molecular subtyping is of significant importance to the recognition of outbreaks of meningococcal disease caused by serogroup C Neisseria meningitidis. We describe the application of multilocus variable number tandem repeat analysis (MLVA) for the molecular subtyping of N. meningitidis and compare its performance to that of pulsed-field gel electrophoresis (PFGE).

[Distribution of HBV genotypes in the Czech population--pilot study].

A compact structure of the hepatitis B virus genome does not provide much space for development of mutations capable of further replication. In spite of that, 7 genotypes have been described so far. Discovery of the hepatitis B virus (HBV) genome diversity led to a range of further questions.

Association of Salmonella enterica serovar enteritidis yafD with resistance to chicken egg albumen.

Salmonella enterica serovar Enteritidis is a major cause of food-borne diseases in industrialized countries. The incidence of S. enterica serovar Enteritidis infections has increased substantially in recent decades, and S.

The global regulator ArcA controls resistance to reactive nitrogen and oxygen intermediates in Salmonella enterica serovar Enteritidis.

Salmonella enterica serovar Enteritidis is a major cause of food-borne diseases associated with consumption of shell eggs. Clinical isolates of S. enterica serovar Enteritidis exhibit a wide spectrum of virulence in mice.

Genotypic distribution of TT virus (TTV) in a Czech population: evidence for sexual transmission of the virus.

Background: TTV is a new DNA virus distinguished by its high degree of strain heterogeneity. The geographic clustering of viral genotypes suggests frequent community transmission. While no specific human disease has yet been linked to it, a transmission mechanism that facilitates strain diversity may eventually select for a strain that will become pathogenic.

Genotypic and epidemiologic characteristics of hepatitis C virus infections among recent injection drug user and nonuser populations.

The recent surge in injection drug use (IDU) in Prague, Czech Republic, provided an opportunity to compare the distribution of hepatitis C virus (HCV) genotypes among recent injection drug users and nonusers. We provide evidence that the most common HCV subtype, 1b, has been circulating in Prague longer than the other subtypes but that IDU practice has magnified its recent prevalence, and that the primary drug of choice among IDU subjects appears to influence the prevalence of a particular HCV subtype.

Bcl-2 inhibits apoptosis induced by mitochondrial uncoupling but does not prevent mitochondrial transmembrane depolarization.

Bcl-2 overexpression protects cells from apoptosis induced by many cytotoxic agents. In this study, we investigated the effects of uncoupling mitochondrial electron transport in both HL60 wild-type and Bcl-2-overexpressing cells using the protonophore carbonyl cyanide m-chlorophenylhydrazone. We found that uncoupling mitochondrial electron transport induced apoptosis in wild-type, but not in Bcl-2-overexpressing cells.

Inhibition of store-operated calcium entry in human lymphocytes by radiation: protection by glutathione.

The influence of gamma radiation on basal compared to activation-dependent Ca(2+) influx in human lymphocytes was investigated. A new quantitative fluorescence technique termed differential ratiometric fluorescence spectroscopy (DRFS) was employed. DRFS facilitated the real-time detection of changes in fluorescence in experimental and control cell samples simultaneously, enabling the resolution of acute moderate changes ( congruent with10-30%) in Ca(2+) (manganese) influx after exposure to ionizing radiation and other oxidant interventions.