Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice

BACKGROUND: The worldwide appearance of drug-resistant strains of H. pylori motivates a search for new agents with therapeutic potential against this family of bacteria that colonizes the stomach, and is associated with adenocarcinoma development. This study was designed to assess in vitro the anti-H. pylori potential of cathelicidin LL-37 peptide, which is naturally present in gastric juice, its optimized synthetic analog WLBU2, and the non-peptide antibacterial agent ceragenin CSA-13. RESULTS: In agreement with previous studies, increased expression of hCAP-18/LL-37 was observed in gastric mucosa obtained from H. pylori infected subjects. MBC (minimum bactericidal concentration) values determined in nutrient-containing media range from 100-800 μg/ml for LL-37, 17.8-142 μg/ml for WLBU2 and 0.275-8.9 μg/ml for ceragenin CSA-13. These data indicate substantial, but widely differing antibacterial activities against clinical isolates of H. pylori. After incubation in simulated gastric juice (low pH with presence of pepsin) CSA-13, but not LL-37 or WLBU2, retained antibacterial activity. Compared to LL-37 and WLBU2 peptides, CSA-13 activity was also more resistant to inhibition by isolated host gastric mucins. CONCLUSION: These data indicate that cholic acid-based antimicrobial agents such as CSA-13 resist proteolytic degradation and inhibition by mucin and have potential for treatment of H. pylori infections, including those caused by the clarithromycin and/or metronidazole-resistant strains

Radio Regulation Revisited: Coase, the FCC, and the Public Interest

It is now more than forty years since Ronald Coase’s seminal article on the Federal Communications Commission first appeared in the pages of the Journal of Law and Economics.1 The article remains important for a number of reasons, not least of which is that it offered his first articulation of the Coase Theorem.2 Of even greater importance for our purposes, the article literally redefined the terms of debate over American broadcast regulation, in both historical and contemporary treatments of the subject. Focusing particularly on the development of radio regulation, Coase rejected the prevailing notion that the establishment of the Federal Communications Commission (FCC) served the public interest. Rather, he concluded that its creation had been a mistake, the product of faulty economic reasoning. The complex regulatory apparatus developed under the Federal Radio Act of 1927 and recodified in the Federal Communications Act of 1934 was built on the flawed assumption that scarce resources—in this case the radio spectrum—had to be allocated by government fiat. A more efficient solution, Coase maintained, would have been to allocate the spectrum like any other scarce resource, on the basis of well-defined property rights and a free market guided by the price mechanism. Indeed, this is why he suggested that the spectrum ought to be cut up and sold at auction rather than regulated by the federal government.

Quantifying Threat or Challenge Response of Undergraduate Paramedicine Students During High-Stress Clinical Scenarios - A Narrative Review

Paramedic work can be stressful. Encountering clinically unwell patients, long shift hours and dealing with the unknown expose paramedics to mental, physical and emotional stress. In the learning environment, these types of stresses are difficult for educators to replicate. Traditionally, students have been tested under pressure in scenario-based situations as a means of stress inoculation. However, the literature is unclear as to whether this enhances or hinders learning. A recent scoping review identified an acceptable level of stress during simulation can be beneficial, although a level of a balance is required. Too much stress can hinder learning and lead to underperformance. Ideally, high-acuity patient scenarios should be designed to invoke a challenging state of appraisal in the student to support both their learning and knowledge retention. To obtain an understanding of how students appraise these types of scenarios, quantitative physiological and psychometric data needs to be obtained and analyzed. However, across the health care education literature, inconsistent methodologies and a variety of physiological and cognitive measures make it challenging to draw firm conclusions. This narrative review searched three prominent databases using common search terms to produce a subset of high-quality publications that we thought were most pertinent and insightful. Our paper establishes recommendations for appropriate physiological assessment and interpterion of challenge appraisal in students undertaking high-stress, low-frequency clinical scenarios

Too stressed to think? A scoping review of the literature for healthcare educators utilising high acuity clinical scenarios.

The practise of paramedicine can be highly stressful particularly where urgent lifesaving decisions need to be made. Traditionally, educators have adopted the approach of placing students in simulated stressful situations as a way of learning to cope with these challenges. It is unclear from the literature whether traditional stress inoculation enhances or hinders learning. This scoping review aims to identify and examine both the peer-reviewed and grey literature reporting physiological stress responses to high-acuity scenarios in paramedicine and cognate healthcare disciplines

The impact of substance use on brain structure in people at high risk of developing schizophrenia

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances

Promoting Vulgarity by Teaching Slang in the Classroom

Mark Twain once said, "Indecency, vulgarity, obscenity -- these are strictly confined to man; he invented them. Among the higher animals there is no trace of them." I would like to suggest that we, as language teachers, need to be a little more open to the vulgar vernacular. I use "vulgar" in its original sense -- "common, ordinary" -- from the Latin vulgaris, "of or pertaining to the common people." Essentially, then, I wish to argue that we need to teach our students the use more vulgarity in their speech

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF

A framework for experimental-data-driven assessment of Magnetized Liner Inertial Fusion stagnation image metrics

A variety of spherical crystal x-ray imager (SCXI) diagnostics have been developed and fielded on Magnetized Liner Inertial Fusion (MagLIF) experiments at the Sandia National Laboratories Z-facility. These different imaging modalities provide detailed insight into different physical phenomena such as mix of liner material into the hot fuel, cold liner emission, or reduce impact of liner opacity. However, several practical considerations ranging from the lack of a consistent spatial fiducial for registration to different point-spread-functions and tuning crystals or using filters to highlight specific spectral regions make it difficult to develop broadly applicable metrics to compare experiments across our stagnation image database without making significant unverified assumptions. We leverage experimental data for a model-free assessment of sensitivities to instrumentation-based features for any specified image metric. In particular, we utilize a database of historical and recent MagLIF data including $N_{\text{scans}} = 139$ image plate scans gathered across $N_{\text{exp}} = 67$ different experiments to assess the impact of a variety of features in the experimental observations arising from uncertainties in registration as well as discrepancies in signal-to-noise ratio and instrument resolution. We choose a wavelet-based image metric known as the Mallat Scattering Transform for the study and highlight how alternate metric choices could also be studied. In particular, we demonstrate a capability to understand and mitigate the impact of signal-to-noise, image registration, and resolution difference between images. This is achieved by utilizing multiple scans of the same image plate, sampling random translations and rotations, and applying instrument specific point-spread-functions found by ray tracing to high-resolution datasets, augmenting our data in an effectively model-free fashion.Comment: 17 pages, 14 figure

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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