Vortical Structures Promote Atheroprotective Wall Shear Stress Distributions in a Carotid Artery Bifurcation Model.

Carotid artery diseases, such as atherosclerosis, are a major cause of death in the United States. Wall shear stresses are known to prompt plaque formation, but there is limited understanding of the complex flow structures underlying these stresses and how they differ in a pre-disposed high-risk patient cohort. A 'healthy' and a novel 'pre-disposed' carotid artery bifurcation model was determined based on patient-averaged clinical data, where the 'pre-disposed' model represents a pathological anatomy. Computational fluid dynamic simulations were performed using a physiological flow based on healthy human subjects. A main hairpin vortical structure in the internal carotid artery sinus was observed, which locally increased instantaneous wall shear stress. In the pre-disposed geometry, this vortical structure starts at an earlier instance in the cardiac flow cycle and persists over a much shorter period, where the second half of the cardiac cycle is dominated by perturbed secondary flow structures and vortices. This coincides with weaker favorable axial pressure gradient peaks over the sinus for the 'pre-disposed' geometry. The findings reveal a strong correlation between vortical structures and wall shear stress and imply that an intact internal carotid artery sinus hairpin vortical structure has a physiologically beneficial role by increasing local wall shear stresses. The deterioration of this beneficial vortical structure is expected to play a significant role in atherosclerotic plaque formation.

Shear stress metrics associated with pro-atherogenic high-risk anatomical features in a carotid artery bifurcation model.

BACKGROUND: Diseases associated with atherosclerotic plaques in the carotid artery are a major cause of deaths in the United States. Blood-flow-induced shear-stresses are known to trigger plaque formation. Prior literature suggests that the internal carotid artery sinus is prone to atherosclerosis, but there is limited understanding of why only certain patients are predisposed towards plaque formation. METHODS: We computationally investigate the effect of vessel geometry on wall-shear-stress distribution by comparing flowfields and wall-shear-stress-metrics between a low-risk and a novel predisposed high-risk carotid artery bifurcation anatomy. Both models were developed based on clinical risk estimations and patient-averaged anatomical features. The high-risk geometry has a larger internal carotid artery branching angle and a lower internal-to-carotid-artery-diameter-ratio. A patient-averaged physiological carotid artery inflow waveform is used. FINDINGS: The high-risk geometry experiences stronger flow separation in the sinus. Furthermore, it experiences a more equal flow split at the bifurcation, thereby reducing internal carotid artery flowrate and increasing atherosclerosis-prone low-velocity areas. Lowest time-averaged-wall-shear-stresses are present at the sinus outer wall, where plaques are often found, for both geometries. The high-risk geometry has significantly high, unfavorable oscillatory-shear-index values not found in the low-risk geometry. High oscillatory-shear-index areas are located at the vessels outside walls distal to the bifurcation and on the sinus wall. INTERPRETATION: These results highlight the effectiveness of oscillatory-shear-index, to augment classical time-averaged-wall-shear-stress, in evaluating pro-atherogenic geometry features. Furthermore, the flow split at the bifurcation is a promising clinical indicator for atherosclerosis risk as it can be directly accessed using clinical imaging, whereas shear-stress-metrics cannot.

Single Lung Transplant Remains a Viable Option for Patients With Severe Secondary Pulmonary Hypertension.

BACKGROUND: Although double lung transplant is recommended in patients with severe secondary pulmonary hypertension (SPH), our institutional experiences suggest a role for single lung transplant in these patients. Here, we review our experience prioritizing single lung transplant in patients with SPH to minimize their surgical burden. METHODS: We conducted a retrospective review of our lung transplant database to identify patients with SPH who underwent single lung transplant. Patients were stratified as either mild SPH (mean pulmonary artery pressure 25-40 mm Hg) or severe SPH (mean pulmonary artery pressure >40 mm Hg). Singe lung recipients without PH transplanted over the same time were also examined. RESULTS: Between January 2017 and December 2019, 318 patients underwent single lung transplantation; 217 had mild SPH (68%), and 59 had severe SPH (18.5%). Forty-two patients without PH underwent single lung transplant. When the groups were compared, significantly higher pulmonary vascular resistance was noted in the severe SPH group, and obesity was noted in both the mild and severe SPH groups. Although the severe SPH group required more intraoperative cardiopulmonary support (37.3% versus 10.3% versus 4.7%, P < 0.05), there were no significant differences in most major postoperative parameters, including the duration of postoperative mechanical ventilation or the incidence of severe primary graft dysfunction. Survival 1 y posttransplant was not significantly different among the groups (93.2% versus 89.4% versus 92.9%, P = 0.58). CONCLUSIONS: Our experience supports the option of single lung transplantation with appropriate intraoperative mechanical circulatory support in patients with SPH. This strategy is worth pursuing, especially with ongoing donor lung shortages.

Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date.

Asthma is a complex heterogeneous disease defined by chronic inflammation of the airways. Patients present with wheezing, chest tightness, cough and shortness of breath. Bronchial hyperresponsiveness and variable expiratory airflow limitation are hallmark features. About 3.6-6.1% of patients, despite receiving high-dose inhaled corticosteroids (ICS) and a second controller medication, report persistent symptoms referred to as severe asthma. Uncontrolled severe asthma is associated with increased mortality, morbidity, diminished quality of life and increased health expenditures. The development of modern biological therapy has revolutionized severe asthma treatment. By targeting specific chemokines, asthma control has drastically improved, resulting in better quality of life, less emergency department visits and inpatient admissions, and decreased chronic systemic corticosteroid utilization. Despite these advances, there remains a subset of asthma patients who remain symptomatic with poor quality of life and heavy utilization of the healthcare system. Recently attention has been given to pharmaceutical therapy directed at receptors and cytokines on the epithelial layer of the lung referred to as "alarmins". Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like receptor family found on the epithelial layer of the lung that releases a cytokine cascade inducing eosinophilic inflammation, mucus production and airflow obstruction in asthmatics. Tezepelumab is the first investigational monoclonal antibody that inhibits TSLP. Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV1 and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.

Macro-Rheology Characterization of Gill Raker Mucus in the Silver Carp, Hypophthalmichthys molitrix.

The silver carp, Hypophthalmichthys molitrix, is an invasive planktivorous filter feeder fish that infested the natural waterways of the upper Mississippi River basin due to its highly efficient filter feeding mechanism. The characteristic organs called gill rakers (GRs), found in many such filter feeders, facilitate the efficient filtration of food particles such as phytoplankton that are of a few microns in size. The motivation to investigate the rheology of the GR mucus stems from our desire to understand its role in aiding the filter feeding process in the silver carp. The mucus-rich fluid, in a 'thick and sticky' state may facilitate the adhesion of food particulates. The permeation and transport through the GR membrane are facilitated by the action of external shear forces that induce varying shear strain rates. Therefore, mucus rheology can provide a vital clue to the tremendous outcompeting nature of the silver carp within the pool of filter feeding fish. Based on this it was posited that GR mucus may provide an adhesive function to food particles and act as a transport vehicle to assist in the filter feeding process. The main objective of the protocol is to determine the yield stress of the mucus, attributed to the minimum shear stress required to initiate flow at which irreversible plastic deformation is first observed across a structured viscoelastic material. Accordingly, rheological properties of the GR mucus, i.e., viscosity, storage, and loss moduli, were investigated for its non-Newtonian, shear-thinning nature using a rotational rheometer.   A protocol presented here is employed to analyze the rheological properties of mucus extracted from the gill rakers of a silver carp, fished at Hart Creek location of the Missouri River. The protocol aims to develop an effective strategy for rheological testing and material characterization of mucus assumed to be a structured viscoelastic material.

COVID-19 in lung transplant recipients.

Solid organ transplant recipients are considered at high risk for COVID-19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID-19 infection in lung transplant recipients. Here we report 8 cases of COVID-19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients.

Onset of Effect, Changes in Airflow Obstruction and Lung Volume, and Health-Related Quality of Life Improvements with Benralizumab for Patients with Severe Eosinophilic Asthma: Phase IIIb Randomized, Controlled Trial (SOLANA).

OBJECTIVE: In the SOLANA trial, we sought to physiologically characterize benralizumab's onset of effect and maintenance of that effect for patients with severe eosinophilic asthma. METHODS: SOLANA (NCT02869438) was a multicenter, randomized, double-blind, parallel-group, placebo-controlled, Phase IIIb study conducted at 49 centers in six countries (Chile, Germany, Hungary, the Philippines, South Korea, and the United States). Eligible patients with baseline blood eosinophil counts ≥300 cells/µL were randomized to subcutaneous benralizumab (30 mg) or placebo administered at Days 0, 28, and 56. The primary endpoint was the average change from baseline in prebronchodilator forced expiratory volume in 1 s (pre-BD FEV1) during the Day 28‒Day 84 period for benralizumab vs placebo. Secondary endpoints included patient-reported outcomes (PROs). A subset of patients participated in a whole-body plethysmography substudy. Safety was also assessed. RESULTS: In total, 233 patients were randomized to benralizumab (n=118) or placebo (n=115). Improvement from baseline in pre-BD FEV1 with benralizumab 30 mg was not statistically significant compared with placebo (least-squares mean change difference [95% confidence interval] 57 mL [-22 to 135]; p=0.16). Compared with placebo, benralizumab demonstrated early (Day 7) nonstatistically significant improvements in whole-body plethysmography assessments of hyperinflation and clinically meaningful improvements in PRO measures (Asthma Control Questionnaire 6 at Day 14 and St. George's Respiratory Questionnaire at Day 28), which were maintained over the treatment period. Benralizumab's safety profile was commensurate with previously reported studies. CONCLUSION: The observed early changes in lung volume despite relatively small improvements in airflow obstruction suggest that the anti-inflammatory effect of benralizumab may be manifested as deflation over time for patients with hyperinflation, who potentially have a greater degree of airway remodeling. This early effect could partially explain the rapid PRO improvements observed for certain patients.

Large-area high-speed scanning probe microscopy using legacy scanners.

In scanning probe microscopy, the scanner dynamically positions the sample relative to the probe, and the upper limit of the imaging speed is governed primarily by the first eigenfrequency of the scanner. The mechanical oscillations of the scanner-even when it operates far from resonance-give rise to image artifacts and negatively affect the image resolution. This paper analytically and experimentally investigates the scanner's dynamics at high scan rates upon scanning over a large area. At slow scan speeds, the frequency spectra of the microcantilever's deflection signal exhibit only the excitation frequency and its harmonics; in contrast, at high scan speeds, the spectra exhibit sidebands centered around the excitation harmonics and separated from them by the scanner's eigenfrequency. Exploiting this phenomenon, a scanner dynamics-based method is proposed to reconstruct the surface topography, and, thereby, to reduce the oscillation-induced image artifacts. The method is proven for a variety of sample surfaces at very high scan rates up to 59.2 Hz (corresponding to a linear speed of 4.74 mm/s) upon scanning over a 40 µm × 40 µm area and is successfully demonstrated to be able to virtually eliminate any image artifacts. A nearly ten-fold increase in the scan rate is demonstrated using even a legacy scanner, with no changes required to the hardware.

A 10-Year Analysis of Head and Neck Injuries Involving Nonpowder Firearms.

Objectives Firearms have an enduring and visible presence within American culture. However, the public health impact of nonpowder firearms and other "toy" guns has not been fully studied. These guns-including BB guns (ie, ball bearing), paintball guns, and pellet guns-are typically marketed to a younger audience. The objective of this study is to analyze head and neck injuries related to nonpowder firearms. Study Design Cross-sectional analysis of a national database. Setting Academic medical center. Subjects and Methods The National Electronic Injury Surveillance System was queried for head and neck injuries involving nonpowder guns, including air, BB, and pellet guns, and associated ammunition. Analysis of age, sex, incidence, injury location, and diagnosis was performed. Results From 2005 to 2014, there were 1695 cases recorded, or 55,060 estimated emergency room visits, due to injuries related to nonpowder guns and fired ammunition. The majority of patients were male (80.9%). These injuries were most common in children 6 to 12 years of age (37.9%), followed by those 13 to 18 years old (27.1%) and adults (≥19 years old; 17.8%), while preschool children (0-5 years) represented 17.2%. The most common injury diagnosis was penetrating foreign body (34.9%), followed by lacerations (24.3%) and contusions/abrasions (13.7%). Conclusion Nonpowder and other nonlethal firearm-related injuries to the head and neck region are a frequent source of emergency room visits nationally. Safety measures and public education on a mainstream level are required.

Experimental Investigation of Secondary Flow Structures Downstream of a Model Type IV Stent Failure in a 180° Curved Artery Test Section.

The arterial network in the human vasculature comprises of ubiquitously present blood vessels with complex geometries (branches, curvatures and tortuosity). Secondary flow structures are vortical flow patterns that occur in curved arteries due to the combined action of centrifugal forces, adverse pressure gradients and inflow characteristics. Such flow morphologies are greatly affected by pulsatility and multiple harmonics of physiological inflow conditions and vary greatly in size-strength-shape characteristics compared to non-physiological (steady and oscillatory) flows (1 - 7). Secondary flow structures may ultimately influence the wall shear stress and exposure time of blood-borne particles toward progression of atherosclerosis, restenosis, sensitization of platelets and thrombosis (4 - 6, 8 - 13). Therefore, the ability to detect and characterize these structures under laboratory-controlled conditions is precursor to further clinical investigations. A common surgical treatment to atherosclerosis is stent implantation, to open up stenosed arteries for unobstructed blood flow. But the concomitant flow perturbations due to stent installations result in multi-scale secondary flow morphologies (4 - 6). Progressively higher order complexities such as asymmetry and loss in coherence can be induced by ensuing stent failures vis-à-vis those under unperturbed flows (5). These stent failures have been classified as "Types I-to-IV" based on failure considerations and clinical severity (14). This study presents a protocol for the experimental investigation of the complex secondary flow structures due to complete transverse stent fracture and linear displacement of fractured parts ("Type IV") in a curved artery model. The experimental method involves the implementation of particle image velocimetry (2C-2D PIV) techniques with an archetypal carotid artery inflow waveform, a refractive index matched blood-analog working fluid for phase-averaged measurements (15 - 18). Quantitative identification of secondary flow structures was achieved using concepts of flow physics, critical point theory and a novel wavelet transform algorithm applied to experimental PIV data (5, 6, 19 - 26).

Characterization of cadmium-resistant bacteria for its potential in promoting plant growth and cadmium accumulation in Sesbania bispinosa root.

The cadmium (Cd) resistant bacteria were isolated from soils of Damanganga river, Vapi, and identified 11 potential Cd resistant bacteria based on 16S rDNA sequences. The Cd resistant bacteria belonged to four different genera: Providencia spp., Morganella sp., Stenotrophomonas sp., and Bacillus spp. The assessment of plant growth-promoting (PGP) parameters revealed that the Cd tolerant bacteria showed one or more PGP properties. Further, a pot experiment was conducted to elucidate the effects of Cd resistant bacteria on the plant growth and the uptake of Cd by Sesbania bispinosa. The bacterized seedlings recorded 36.0-74.8% and 21.2-32.9% higher root and shoot lengths, respectively, in Cd amended soil compared with control. The Cd mobilization in the root of S. bispinosa by microbial inoculants ranged from 0.02 ± 0.01 to 1.11 ± 0.06 ppm. The enhanced concentrations of Cd accumulation in S. bispinosa roots correspond to the effect of the bacterial strains on metal mobilization in soil. The present observations showed that the Cd resistant strains protect the plants against the inhibitory effects of Cd, probably due to the production of PGP properties. The present results provided a new insight into the phytoremediation of Cd contaminated soil.

High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories.

A novel scan trajectory for high-speed scanning probe microscopy is presented in which the probe follows a two-dimensional Lissajous pattern. The Lissajous pattern is generated by actuating the scanner with two single-tone harmonic waveforms of constant frequency and amplitude. Owing to the extremely narrow frequency spectrum, high imaging speeds can be achieved without exciting the unwanted resonant modes of the scanner and without increasing the sensitivity of the feedback loop to the measurement noise. The trajectory also enables rapid multiresolution imaging, providing a preview of the scanned area in a fraction of the overall scan time. We present a procedure for tuning the spatial and the temporal resolution of Lissajous trajectories and show experimental results obtained on a custom-built atomic force microscope (AFM). Real-time AFM imaging with a frame rate of 1 frame s⁻¹ is demonstrated.

Juxtaposed half-cystines as disulphide bridged partners in protein tertiary structure.

Disulphide bridges involving juxtaposed half-cystines are observed in a number of protein three-dimensional structures analyzed from the Protein Data Bank. These disulphide bridges comprise a 'ring of 8-atoms' corresponding to Calpha1-C'-N-Calpha2-Cbeta2-Sgamma2-Sgamma1-Cbeta1-Calpha1 in the two half-cystines. The presence of such disulphide bridges introduces a 'bend' or 'kink' in the protein polypeptide chain.

Analysis of disulphide bond connectivity patterns in protein tertiary structure.

The analysis of disulphide bond containing proteins in the Protein Data Bank (PDB) revealed that out of 27,209 protein structures analyzed, 12,832 proteins contain at least one intra-chain disulphide bond and 811 proteins contain at least one inter-chain disulphide bond. The intra-chain disulphide bond containing proteins can be grouped into 256 categories based on the number of disulphide bonds and the disulphide bond connectivity patterns (DBCPs) that were generated according to the position of half-cystine residues along the protein chain. The PDB entries corresponding to these 256 categories represent 509 unique SCOP superfamilies. A simple web-based computational tool is made freely available at the website that allows flexible queries to be made on the database in order to retrieve useful information on the disulphide bond containing proteins in the PDB. The database is useful to identify the different SCOP superfamilies associated with a particular disulphide bond connectivity pattern or vice versa. It is possible to define a query based either on a single field or a combination of the following fields, i.e., PDB code, protein name, SCOP superfamily name, number of disulphide bonds, disulphide bond connectivity pattern and the number of amino acid residues in a protein chain and retrieve information that match the criterion. Thereby, the database may be useful to select suitable protein structural templates in order to model the more distantly related protein homologs/analogs using the comparative modeling methods.