The sliding motility of the bacilliform virions of Influenza A viruses.

Influenza A virus (IAV) infection relies on the action of the hemagglutinin (HA) and neuraminidase (NA) membrane proteins. The HA ligands anchor the IAV virion to the cell's surface by binding the sialic acid (SA) present on the host's receptors while NA is an enzyme capable of cleaving the SA from the extracellular environment. It is believed that the activity of NA ligands increases the motility of the virions favoring the propagation of the infection. In this work, we develop a numerical framework to study the dynamics of a virion moving across the cell surface for timescales much bigger than the typical ligand-receptor reaction times. We find that the rates controlling the ligand-receptor reactions and the maximal distance at which a pair of ligand-receptor molecules can interact greatly affect the motility of the virions. We also report on how different ways of organizing the two types of ligands on the virions' surface result in different types of motion that we rationalize using general principles. In particular, we show how the emerging motility of the virion is less sensitive to the rate controlling the enzymatic activity when NA ligands are clustered.

Sliding across a surface: Particles with fixed and mobile ligands.

A quantitative model of the mobility of ligand-presenting particles at the interface is pivotal to understanding important systems in biology and nanotechnology. In this work, we investigate the emerging dynamics of particles featuring ligands that selectively bind receptors decorating an interface. The formation of a ligand-receptor complex leads to a molecular bridge anchoring the particle to the surface. We consider systems with reversible bridges in which ligand-receptor pairs bind/unbind with finite reaction rates. For a given set of bridges, the particle can explore a tiny fraction of the surface as the extensivity of the bridges is finite. We show how, at timescales longer than the bridges' lifetime, the average position of the particle diffuses away from its initial value. We distill our findings into two analytic equations for the sliding diffusion constant of particles carrying mobile and fixed ligands. We quantitatively validate our theoretical predictions using reaction-diffusion simulations. We compare our findings with results from recent literature studies and discuss the molecular parameters that likely affect the particle's mobility most. Our results, along with recent literature studies, will allow inferring the microscopic parameters at play in complex biological systems from experimental trajectories.

Disclosure of Adverse Events: A Guide for Clinicians.

INTRODUCTION: Children's Hospitals' Solutions for Patient Safety (SPS) acknowledged a recommendation from the American Academy of Pediatrics to develop education programs on the communication of adverse events with patients and families. SPS set out to create a guide that would outline a standardized disclosure process and provide a training curriculum and tools so that providers would feel better prepared to have effective disclosure conversations. METHODS: SPS disclosure work began with the development of a project team made up of 9 network hospitals. The team utilized key driver diagrams and process maps to show the relationship between the project aims, key drivers, and specific interventions. The team developed a training curriculum, guide, and tools for each area of improvement. To ensure these were effective, they were tested using case studies and plan-do-study-act cycles. RESULTS: One of the cohort hospitals piloted the curriculum and tools, training 48 physicians, nurses, executives, and other allied health professionals. Pretest to posttest scores improved from an average of 82.7% to 90.2%. Survey feedback was favorable with 100% of respondents noting that they strongly agree or agree that attending this educational activity increased or improved their competency, performance, and patient outcomes. CONCLUSIONS: Initial testing suggests that the developed curriculum is empowering for frontline clinicians. Materials are available in an electronic format on the SPS external website. As member hospitals implement these materials, they will be evaluating learner satisfaction and provider usage. SPS will seek out feedback from these hospitals to further develop the materials and support clinicians.

The Effect of Breathing, Movement, and Meditation on Psychological and Physical Symptoms and Inflammatory Biomarkers in Inflammatory Bowel Disease: A Randomized Controlled Trial.

BACKGROUND: This study evaluated the effects of the Breath-Body-Mind Workshop (BBMW) (breathing, movement, and meditation) on psychological and physical symptoms and inflammatory biomarkers in inflammatory bowel disease (IBD). METHODS: Twenty-nine IBD patients from the Jill Roberts IBD Center were randomized to BBMW or an educational seminar. Beck Anxiety Inventory, Beck Depression Inventory, Brief Symptom Inventory 18, IBD Questionnaire, Perceived Disability Scale, Perceived Stress Questionnaire, Digestive Disease Acceptance Questionnaire, Brief Illness Perception Questionnaire, fecal calprotectin, C-reactive protein, and physiological measures were obtained at baseline and weeks 6 and 26. RESULTS: The BBMW group significantly improved between baseline and week 6 on Brief Symptom Inventory 18 (P = 0.02), Beck Anxiety Inventory (P = 0.02), and IBD Questionnaire (P = 0.01) and between baseline and week 26 on Brief Symptom Inventory 18 (P = 0.04), Beck Anxiety Inventory (P = 0.03), Beck Depression Inventory (P = 0.01), IBD Questionnaire (P = 0.01), Perceived Disability Scale (P = 0.001), and Perceived Stress Questionnaire (P = 0.01) by paired t tests. No significant changes occurred in the educational seminar group at week 6 or 26. By week 26, median C-reactive protein values decreased significantly in the BBMW group (P = 0.01 by Wilcoxon signed-rank test) versus no significant change in the educational seminar group. CONCLUSIONS: In patients with IBD, participation in the BBMW was associated with significant improvements in psychological and physical symptoms, quality of life, and C-reactive protein. Mind-body interventions, such as BBMW, which emphasize Voluntarily Regulated Breathing Practices, may have significant long-lasting benefits for IBD symptoms, anxiety, depression, quality of life, and inflammation. BBMW, a promising adjunctive treatment for IBD, warrants further study.

Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease.

RATIONALE: There is increasing evidence for the presence of autoantibodies in chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an essential component in COPD pathogenesis and can lead to increased levels of highly reactive carbonyls in the lung, which could result in the formation of highly immunogenic carbonyl adducts on "self" proteins. OBJECTIVES: To determine the presence of autoantibodies to carbonyl-modified protein in patients with COPD and in a murine model of chronic ozone exposure. To assess the extent of activated immune responses toward carbonyl-modified proteins. METHODS: Blood and peripheral lung were taken from patients with COPD, age-matched smokers, and nonsmokers with normal lung function, as well as patients with severe persistent asthma. Mice were exposed to ambient air or ozone for 6 weeks. Antibody titers were measured by ELISA, activated compliment deposition by immunohistochemistry, and cellular activation by ELISA and fluorescence-activated cell sorter. MEASUREMENTS AND MAIN RESULTS: Antibody titer against carbonyl-modified self-protein was significantly increased in patients with Global Initiative for Chronic Obstructive Lung Disease stage III COPD compared with control subjects. Antibody levels inversely correlated with disease severity and showed a prevalence toward an IgG1 isotype. Deposition of activated complement in the vessels of COPD lung as well as autoantibodies against endothelial cells were also observed. Ozone-exposed mice similarly exhibited increased antibody titers to carbonyl-modified protein, as well as activated antigen-presenting cells in lung tissue and splenocytes sensitized to activation by carbonyl-modified protein. CONCLUSIONS: Carbonyl-modified proteins, arising as a result of oxidative stress, promote antibody production, providing a link by which oxidative stress could drive an autoimmune response in COPD.

Human idiopathic and neurogenic overactive bladders and the role of M2 muscarinic receptors in contraction.

OBJECTIVES: This study examines whether M(2) receptors contribute to direct contraction of the detrusor in human neurogenic and idiopathic overactive bladders. METHODS: Control detrusor muscle was obtained from patients undergoing cystectomy for bladder cancer, whilst overactive detrusor muscle was obtained from patients undergoing clam cystoplasty for idiopathic or neurogenic detrusor overactivity. The affinities of a range of subtype selective antagonists (DAMP, darifenacin, methoctramine R0-320-6206, and pirenzepine) were obtained in tissue bath experiments by using carbachol as the agonist. These affinity values were then compared with the known affinities for these antagonists at the muscarinic receptor subtypes. RESULTS: An increased sensitivity to carbachol was observed in both the neurogenic and idiopathic overactive detrusors compared with the control human detrusor. The M(2)-selective antagonists (methoctramine, R0-320-6206) and M(1)-selective antagonist (pirenzepine) had low affinities, whilst the M(3)-selective antagonists (4-DAMP and darifenacin) had high affinities for the human detrusor muscarinic receptor in all three groups of tissues. The affinities (pK(B) values) for the five antagonists were consistent with antagonisms at the M(3) receptor in all three groups; Schild plot analysis indicated an action at this single receptor subtype. CONCLUSIONS: Contraction mediated by muscarinic receptors is enhanced in idiopathic and neurogenic overactive detrusors compared with control detrusor. The direct contractile response to carbachol is mediated by the M(3) receptor in both human normal and overactive bladders, indicating no change in receptor subtype contribution to contraction in the disease state.