Ozone exposure limits cardiorespiratory function during maximal cycling exercise in endurance athletes.

Ground-level ozone (O3) is a potent air pollutant well recognized to acutely induce adverse respiratory symptoms and impairments in pulmonary function. However, it is unclear how the hyperpnea of exercise may modulate these effects, and the subsequent consequences on exercise performance. We tested the hypothesis that pulmonary function and exercise capability would be diminished, and symptom development would be increased during peak real-world levels of O3 exposure compared with room air. Twenty aerobically trained participants [13 M, 7 F; maximal O2 uptake (V̇o2max), 64.1 ± 7.0 mL·kg-1·min-1] completed a three-visit double-blinded, randomized crossover trial. Following a screening visit, participants were exposed to 170 ppb O3 or room air (<10 ppb O3) on separate visits during exercise trials, consisting of a 25-min moderate-intensity warmup, 30-min heavy-intensity bout, and a subsequent time-to-exhaustion (TTE) performance test. No differences in O2 uptake or ventilation were observed during submaximal exercise between conditions. During the TTE test, we observed significantly lower end-exercise O2 uptake (-3.2 ± 4.3%, P = 0.004), minute ventilation (-3.2 ± 6.5%, P = 0.043), tidal volume (-3.6 ± 5.1%, P = 0.008), and a trend toward lower exercise duration in O3 compared with room air (-10.8 ± 26.5%, P = 0.092). As decreases in O2 uptake and alterations in respiratory pattern were also present at matched time segments between conditions, a limitation of oxygen transport seems likely during maximal exercise. A more comprehensive understanding of the direct mechanisms that limit oxygen transport during exercise in high-pollutant concentrations is key for mitigating performance changes.NEW & NOTEWORTHY We demonstrate that in highly trained endurance athletes, exposure to peak real-world levels of O3 air pollution (170 ppb) significantly diminishes O2 uptake along with corresponding changes in ventilation during maximal exercise. As no differences were observed during extended submaximal exercise, a combined effect of effective dose of pollution and exercise intensity on severity of responses seems likely.

Personal strategies to mitigate the effects of air pollution exposure during sport and exercise: a narrative review and position statement by the Canadian Academy of Sport and Exercise Medicine and the Canadian Society for Exercise Physiology.

Air pollution is among the leading environmental threats to health around the world today, particularly in the context of sports and exercise. With the effects of air pollution, pollution episodes (eg, wildfire conflagrations) and climate change becoming increasingly apparent to the general population, so have their impacts on sport and exercise. As such, there has been growing interest in the sporting community (ie, athletes, coaches, and sports science and medicine team members) in practical personal-level actions to reduce the exposure to and risk of air pollution. Limited evidence suggests the following strategies may be employed: minimising all exposures by time and distance, monitoring air pollution conditions for locations of interest, limiting outdoor exercise, using acclimation protocols, wearing N95 face masks and using antioxidant supplementation. The overarching purpose of this position statement by the Canadian Academy of Sport and Exercise Medicine and the Canadian Society for Exercise Physiology is to detail the current state of evidence and provide recommendations on implementing these personal strategies in preventing and mitigating the adverse health and performance effects of air pollution exposure during exercise while recognising the limited evidence base.

Multimodal classification of extremely preterm and term adolescents using the fusiform gyrus: A machine learning approach.

OBJECTIVE: Extremely preterm birth has been associated with atypical visual and neural processing of faces, as well as differences in gray matter structure in visual processing areas relative to full-term peers. In particular, the right fusiform gyrus, a core visual area involved in face processing, has been shown to have structural and functional differences between preterm and full-term individuals from childhood through early adulthood. The current study used multiple neuroimaging modalities to build a machine learning model based on the right fusiform gyrus to classify extremely preterm birth status. METHOD: Extremely preterm adolescents (n = 20) and full-term peers (n = 24) underwent structural and functional magnetic resonance imaging. Group differences in gray matter density, measured via voxel-based morphometry (VBM), and blood-oxygen level-dependent (BOLD) response to face stimuli were explored within the right fusiform. Using group difference clusters as seed regions, analyses investigating outgoing white matter streamlines, regional homogeneity, and functional connectivity during a face processing task and at rest were conducted. A data driven approach was utilized to determine the most discriminative combination of these features within a linear support vector machine classifier. RESULTS: Group differences in two partially overlapping clusters emerged: one from the VBM analysis showing less density in the extremely preterm cohort and one from BOLD response to faces showing greater activation in the extremely preterm relative to full-term youth. A classifier fit to the data from the cluster identified in the BOLD analysis achieved an accuracy score of 88.64% when BOLD, gray matter density, regional homogeneity, and functional connectivity during the task and at rest were included. A classifier fit to the data from the cluster identified in the VBM analysis achieved an accuracy score of 95.45% when only BOLD, gray matter density, and regional homogeneity were included. CONCLUSION: Consistent with previous findings, we observed neural differences in extremely preterm youth in an area that plays an important role in face processing. Multimodal analyses revealed differences in structure, function, and connectivity that, when taken together, accurately distinguish extremely preterm from full-term born youth. Our findings suggest a compensatory role of the fusiform where less dense gray matter is countered by increased local BOLD signal. Importantly, sub-threshold differences in many modalities within the same region were informative when distinguishing between extremely preterm and full-term youth.

Development of the mentalizing network structures and theory of mind in extremely preterm youth.

Adolescents born preterm (<37 weeks of gestation) are at elevated risk for deficits in social cognition and peer relationships. Theory of Mind (ToM) is a complex form of social cognition important for regulating social interactions. ToM and the underlying mentalizing network continue to develop across adolescence. The present study recruited 48 adolescents (12-17 years old) who were either born extremely preterm (EPT; <28 weeks of gestation) or full-term (FT) at birth. Cortical thickness, gray matter volume and surface area were measured in four regions of the mentalizing network: the temporoparietal junction, anterior temporal cortex, posterior superior temporal sulcus and frontal pole (mBA10). We also assessed the adolescents' performance on a ToM task. Findings revealed both group differences and group-by-age interaction effects in the gray matter indices within the temporal lobe regions of the mentalizing network. The EPT group also performed significantly worse than the FT group on the ToM task. The cortical structural measures that discriminated the EPT and FT groups were not related to ToM performance. These results highlight altered developmental changes in brain regions underlying mentalizing functions in EPT adolescents relative to FT controls.

The Acute Effects of Exercising in Air Pollution: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: The acute effects of air pollution (AP) exposure during physical activity have been studied. However, comprehensive systematic reviews are lacking, particularly regarding moderate-to-vigorous physical activity (MVPA). OBJECTIVE: Our objective was to determine the acute health- and exercise-related effects of AP exposure during a bout of MVPA in healthy individuals. METHODS: We searched for randomized controlled trials in MEDLINE, Embase, Cochrane CENTRAL, SPORTDiscus, Agricultural and Environmental Science Database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Registry, and the World Health Organization (WHO) International Clinical Trials Registry Platform up to July 2020 without language or date restrictions. Studies including healthy subjects engaging in a bout of MVPA while exposed to one or more of the following air pollutants were eligible: particulate matter, black carbon, carbon monoxide, nitrogen dioxide, ozone, diesel exhaust, and traffic-related air pollution (TRAP). Main outcome measures were markers of pulmonary function, symptoms, cardiovascular function, cognitive function, systemic inflammation, and exercise response. The evidence was synthesized by vote counting based on direction of effect. RESULTS: In total, 53 studies were included in the systematic review. Studies employed a heterogeneous mix of exercise protocols, AP interventions, and measured outcomes. Pooled results suggest ozone exposure during MVPA has an adverse effect on pulmonary function (100% [95% confidence interval (CI) 88-100], p < 0.001; high-certainty evidence) and reported symptoms (88% [95% CI 69-96], p < 0.001; low-certainty evidence). The effect of exposure to carbon monoxide, nitrogen dioxide, small engine exhaust, or diesel exhaust during MVPA on health- and exercise-related outcomes is uncertain because of insufficient evidence and the low to very low certainty of available evidence. DISCUSSION: The evidence is strongest for ozone, exposure to which generally induced a reduction in pulmonary function and increased symptoms during MVPA. The research related to other outcome domains remains inconclusive. Although long-term exposure to AP is proven to be hazardous, the evidence for healthy individuals to forgo MVPA during periods of high (non-ozone) pollution remains weak. TRIAL REGISTRATION: Retrospectively registered in PROSPERO (CRD42020188280) on 10 July 2020.

Atypical age-related changes in the structure of the mentalizing network in children with refractory focal epilepsy.

Refractory focal epilepsy (rFE) is commonly comorbid with impaired social functioning, which significantly reduces quality of life. Previous research has identified a mentalizing network in the brain-composed of the anterior temporal cortex, medial prefrontal cortex (mPFC), posterior temporal sulcus (pSTS), and temporoparietal junction-that is thought to play a critical role in social cognition. In typically-developing (TD) youth, this network undergoes a protracted developmental process with cortical thinning and white matter expansion occurring across adolescence. Because epilepsy is associated with both social dysfunction and irregular neural development, we investigated whether gray and white matter in the mentalizing network differed between youth with rFE (n = 22) and TD youth (n = 41) aged 8-21 years. Older age was associated with reduced cortical thickness in the bilateral mPFC in TD youth, but not in rFE youth. Compared to TD youth, rFE youth had greater white matter density in the right pSTS. Our findings suggest that rFE youth show atypical patterns of cortical thickness and white matter density in regions of the brain that are typically associated with social information processing, potentially as a result of ongoing seizures, comorbid conditions, or other illness-related factors. These results encourage future research to examine whether such variations in neural structure are predictive of specific social deficits in rFE youth.

Ventilatory responses to constant load exercise following the inhalation of a short-acting ß2-agonist in a laboratory-controlled diesel exhaust exposure study in individuals with exercise-induced bronchoconstriction.

OBJECTIVE: Individuals with exercise-induced bronchoconstriction (EIB) use ß2-agonists to reduce respiratory symptoms during acute exercise. The resultingbronchodilation could increase the dose of inhaled pollutants and impair respiratory function when exercise is performedin air pollution. We aimed to assess respiratory responses in individuals with EIB when completing a cycling bout while being exposed to diesel exhaust (DE) or filtered air (FA) with and without the inhalation of salbutamol (SAL), a short-acting ß2-agonist. METHODS: In a double-blind, repeated-measures design, 19 participants with EIB (22-33 years of age) completed four visits: FA-placebo (FA-PLA), FA-SAL, DE-PLA, DE-SAL. After the inhalation of either 400 µg of SAL or PLA, participants sat in the exposure chamber for 60 min, breathing either FA or DE (PM2.5 = 300 µg/m3). Participants then cycled for 30 min at 50 % of peak work rate while breathing FA or DE. Respiratory responses were assessed via spirometry, work of breathing (WOB), fractional use of ventilatory capacity (V̇E/V̇E,CAP), area under the maximal expiratory flow-volume curve (MEFVAUC), and dyspnea during and following cycling. RESULTS: Bronchodilation in response to SAL and acute cycling was observed, independent of FA/DE exposure. Specifically, FEV1 was increased by 7.7 % (confidence interval (CI): 7.2-8.2 %; p < 0.01) in response to SAL, and MEFVAUC was increased after cycling by 1.1 % (0.9-1.3 %; p = 0.03). Despite a significant decrease in total WOB by 6.2 J/min (4.7-7.5 J/min; p = 0.049) and a reduction in V̇E/V̇E,CAP by 5.8 % (5-6 %, p < 0.01) in the SAL exposures, no changes were observed in dyspnea. The DE exposure significantly increased V̇E/V̇E,CAP by 2.4 % (0.9-3.9 %; p < 0.01), but this did not affect dyspnea. DISCUSSION: Our findings suggest that the use of SAL prior to moderate-intensity exercise when breathing high levels of DE, does not reduce respiratory function or exercise ventilatory responses for up to 60 min following exercise.

Blunted neural response to emotional faces in the fusiform and superior temporal gyrus may be marker of emotion recognition deficits in pediatric epilepsy.

Individuals with epilepsy are at risk for social cognition deficits, including impairments in the ability to recognize nonverbal cues of emotion (i.e., emotion recognition [ER] skills). Such deficits are particularly pronounced in adult patients with childhood-onset seizures and are already evident in children and adolescents with epilepsy. Though these impairments have been linked to blunted neural response to emotional information in faces in adult patients, little is known about the neural correlates of ER deficits in youth with epilepsy. The current study compared ER accuracy and neural response to emotional faces during functional magnetic resonance imaging (fMRI) in youth with intractable focal epilepsy and typically developing youth. Relative to typically developing participants, individuals with epilepsy showed a) reduced accuracy in the ER task and b) blunted response to emotional faces (vs. neutral faces) in the bilateral fusiform gyri and right superior temporal gyrus (STG). Activation in these regions was correlated with performance, suggesting that aberrant response within these face-responsive regions may play a functional role in ER impairments. Reduced engagement of neural circuits relevant to processing socioemotional cues may be markers of risk for social cognitive deficits in youth with focal epilepsy.

Ultrasound-Assisted Intraosseous Injection of Platelet-Rich Plasma for a Patient With Tibial Plateau Subchondral Bone Marrow Lesion: A Case Presentation and Technical Illustration.

The subchondral bone marrow lesion (BML) has been found to have a significant correlation with pain in osteoarthritis patients. The intraosseous injection with orthobiologics such as platelet-rich plasma (PRP) or bone marrow aspirate concentrate has shown a promising therapeutic effect on BML-related pain. Traditionally, the intraosseous injection was performed with a large caliber trocar to break into the subchondral bone under fluoroscopy guidance and the patient was usually sedated prior to the procedure. In this report, we presented a 55-year-old woman who suffered from refractory right lateral knee pain for three months. The MRI revealed a right lateral tibial plateau subchondral BML, tears of medial and lateral menisci, and a general osteoarthritic appearance. We used ultrasound (US) to guide a 21-gauge needle through a pre-existing cortical break on the Gerdy's tubercle for the intraosseous PRP injection. The contrast was confirmed to reach the subchondral bone of the lateral tibial plateau and the injection reproduced the patient's symptoms. Three weeks later, the patient had significant improvement in the visual analog scale and function. In conclusion, intraosseous injection with PRP is a possibly effective treatment for subchondral BML in knee osteoarthritis, and US can facilitate a smaller gauge needle placement without the need to sedate the patient.

Internalizing symptoms in intractable pediatric epilepsy: Structural and functional brain correlates.

Internalizing disorders (i.e., depression and anxiety) are common comorbidities in people with epilepsy. In adults with epilepsy, comorbid depression or anxiety is associated with worse seizure control and reduced quality of life, and may be linked to specific neural biomarkers. Less is known about brain correlates of internalizing symptoms in pediatric populations. In the current study, we performed a retrospective analysis of 45 youth between the ages of 6 and 18 years old with intractable epilepsy. Individuals were evaluated for internalizing symptoms on the Child Behavior Checklist (CBCL) and underwent magnetic resonance (MR) and fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging as part of the clinical evaluation for surgical treatment of epilepsy. Forty-two percent of patients experienced clinically significant internalizing symptoms based on parent report. Compared with individuals who scored in the normal range, youth with clinical levels of internalizing problems showed overall reductions in cortex volume, as well as widespread reductions in cortical thickness and functional activation in the bilateral occipital/parietal lobe, left temporal regions, and left inferior frontal cortex on MR and PET scans. There were no group differences in amygdala or hippocampus volumes, nor other patient- or illness-related variables such as age, sex, or the type, lateralization, or duration of epilepsy. Results suggest that high rates of internalizing disorders are present in youth with refractory epilepsy. Multifocal reductions in cortical thickness and function may be nonspecific risk factors for clinically meaningful internalizing symptoms in youth with chronic epilepsy. As such, the presence of broad cortical thinning and reduced glucose uptake upon radiological examination may warrant more focused clinical evaluation of psychological symptoms.

Magnetic barcode imaging for contrast agents.

PURPOSE: To demonstrate a new MR imaging approach that unambiguously identifies and quantitates contrast agents based on intrinsic agent properties such as r1 , r2 , r2*, and magnetic susceptibility. The approach is referred to as magnetic barcode imaging (MBI). METHODS: Targeted and bioresponsive contrast agents were imaged in agarose phantoms to generate T1 , T2 , T2*, and quantitative susceptibility maps. The parameter maps were processed by a machine learning algorithm that is trained to recognize the contrast agents based on these parameters. The output is a quantitative map of contrast agent concentration, identity, and functional state. RESULTS: MBI allowed the quantitative interpretation of intensities, removed confounding backgrounds, enabled contrast agent multiplexing, and unambiguously detected the activation and binding states of bioresponsive and targeted contrast agents. CONCLUSION: MBI has the potential to overcome significant limitations in the interpretation, quantitation, and multiplexing of contrast enhancement by MR imaging probes. Magn Reson Med 77:970-978, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Graphene oxide enhances cellular delivery of hydrophilic small molecules by co-incubation.

The delivery of bioactive molecules into cells has broad applications in biology and medicine. Polymer-modified graphene oxide (GO) has recently emerged as a de facto noncovalent vehicle for hydrophobic drugs. Here, we investigate a different approach using native GO to deliver hydrophilic molecules by co-incubation in culture. GO adsorption and delivery were systematically studied with a library of 15 molecules synthesized with Gd(III) labels to enable quantitation. Amines were revealed to be a key chemical group for adsorption, while delivery was shown to be quantitatively predictable by molecular adsorption, GO sedimentation, and GO size. GO co-incubation was shown to enhance delivery by up to 13-fold and allowed for a 100-fold increase in molecular incubation concentration compared to the alternative of nanoconjugation. When tested in the application of Gd(III) cellular MRI, these advantages led to a nearly 10-fold improvement in sensitivity over the state-of-the-art. GO co-incubation is an effective method of cellular delivery that is easily adoptable by researchers across all fields.

Cell labeling via membrane-anchored lipophilic MR contrast agents.

Cell tracking in vivo with MR imaging requires the development of contrast agents with increased sensitivity that effectively label and are retained by cells. Most clinically approved Gd(III)-based contrast agents require high incubation concentrations and prolonged incubation times for cellular internalization. Strategies to increase contrast agent permeability have included conjugating Gd(III) complexes to cell penetrating peptides, nanoparticles, and small molecules which have greatly improved cell labeling but have not resulted in improved cellular retention. To overcome these challenges, we have synthesized a series of lipophilic Gd(III)-based MR contrast agents that label cell membranes in vitro. Two of the agents were synthesized with a multiplexing strategy to contain three Gd(III) chelates (1 and 2) while the third contains a single Gd(III) chelate (3). These new agents exhibit significantly enhanced labeling and retention in HeLa and MDA-MB-231-mcherry cells compared to agents that are internalized by cells (4 and Prohance).

Mechanisms of Gadographene-Mediated Proton Spin Relaxation.

Gd(III) associated with carbon nanomaterials relaxes water proton spins at an effectiveness that approaches or exceeds the theoretical limit for a single bound water molecule. These Gd(III)-labeled materials represent a potential breakthrough in sensitivity for Gd(III)-based contrast agents used for magnetic resonance imaging (MRI). However, their mechanism of action remains unclear. A gadographene library encompassing GdCl3, two different Gd(III)-complexes, graphene oxide (GO), and graphene suspended by two different surfactants and subjected to varying degrees of sonication was prepared and characterized for their relaxometric properties. Gadographene was found to perform comparably to other Gd(III)-carbon nanomaterials; its longitudinal (r1) and transverse (r2) relaxivity is modulated between 12-85 mM-1s-1 and 24-115 mM-1s-1, respectively, depending on the Gd(III)-carbon backbone combination. The unusually large relaxivity and its variance can be understood under the modified Florence model incorporating the Lipari-Szabo approach. Changes in hydration number (q), water residence time (τM), molecular tumbling rate (τR), and local motion (τfast) sufficiently explain most of the measured relaxivities. Furthermore, results implicated the coupling between graphene and Gd(III) as a minor contributor to proton spin relaxation.

High dynamic range processing for magnetic resonance imaging.

PURPOSE: To minimize feature loss in T1- and T2-weighted MRI by merging multiple MR images acquired at different TR and TE to generate an image with increased dynamic range. MATERIALS AND METHODS: High Dynamic Range (HDR) processing techniques from the field of photography were applied to a series of acquired MR images. Specifically, a method to parameterize the algorithm for MRI data was developed and tested. T1- and T2-weighted images of a number of contrast agent phantoms and a live mouse were acquired with varying TR and TE parameters. The images were computationally merged to produce HDR-MR images. All acquisitions were performed on a 7.05 T Bruker PharmaScan with a multi-echo spin echo pulse sequence. RESULTS: HDR-MRI delineated bright and dark features that were either saturated or indistinguishable from background in standard T1- and T2-weighted MRI. The increased dynamic range preserved intensity gradation over a larger range of T1 and T2 in phantoms and revealed more anatomical features in vivo. CONCLUSIONS: We have developed and tested a method to apply HDR processing to MR images. The increased dynamic range of HDR-MR images as compared to standard T1- and T2-weighted images minimizes feature loss caused by magnetization recovery or low SNR.

Analytical methods for characterizing magnetic resonance probes.

The efficiency of Gd(III) contrast agents in magnetic resonance image enhancement is governed by a set of tunable structural parameters. Understanding and measuring these parameters requires specific analytical techniques. This Feature describes strategies to optimize each of the critical Gd(III) relaxation parameters for molecular imaging applications and the methods employed for their evaluation.

Hydrogel-elastomer composite biomaterials: 4. Experimental optimization of hydrogel-elastomer composite fibers for use as a wound dressing.

We report a novel 3-D cavity wound dressing based on a hydrogel-elastomer Interpenetrating Polymer Network (IPN) fabricated into an open-mesh architecture. IPN fibers used to form the dressing were produced by a wet spinning method and optimized in two steps. A factorial experiment was first conducted to identify key parameters that controlled fiber properties. We observed that gelatin wt% played a major role in determining fiber yield, swelling, strength and stability. Other contributing factors included coagulation solution composition, gelatin type, and pre- and post-UV irradiation time. The key factors were then further evaluated individually to achieve a condition that provided a combination of good swelling, mechanical properties and stability. The concentration of the gelatin/HydroThane extrusion solution significantly affected fiber formation and properties, presumably due to the changes in solution viscosity. The effects of pre-UV irradiation were also ascribed to its impact on the solution viscosity and became negligible at higher concentrations when viscosity is mainly controlled by concentration. The composition of the coagulation bath influenced the fiber swelling and wet stress. These results, taken together with our previous studies, suggest that our biomaterial would provide a combination of mechanical and swelling properties suitable for wound dressing applications.

Controlling methicillin resistant Staphyloccocus aureus and Pseudomonas aeruginosa wound infections with a novel biomaterial.

Wound infections, especially those associated with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, offer considerable challenges for clinicians. Our laboratory has recently developed novel composite biomaterials (DRDC) for wound dressing applications, and demonstrated their in vitro bactericidal efficacy. In the present study, we assessed the proliferation of planktonic and sessile Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in porcine full-thickness wounds covered for up to 48 h with either saline- or mafenide acetate-loaded DRDC puffs and meshes. All biomaterials were applied 4 h following bacterial inoculation of the wounds with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, to allow colonization of the tissues and initiation of biofilm formation. The drug-loaded biomaterials eradicated both the planktonic and biofilm bacteria in the wounds within 24 h (p <. 05), irrespective of the bacterial strain or architecture of the dressing. While the wound bioburdens increased in the ensuing 24 h, they remained approximately 2 log(10) colony-forming units (CFU) below (p <. 05) their respective baseline values. Similarly, less than 4 log(10) CFU was recovered in the drug-loaded DRDC biomaterials throughout the study. These data show that the DRDC puffs and meshes are effective in delivering certain medications, such as antimicrobial agents, to the wound bed, suggesting considerable value of this material for treating wounds, especially those with irregular shapes, contours, and depths.