Adriano M. Alencar

Life-support system benefits from noise

Mechanical ventilators are used to provide life support for patients with respiratory failure. But over the long term, these machines can damage the lungs, causing them to collapse and the partial pressure of oxygen in the arteries to drop to abnormally low values. In conventional mechanical ventilation, the respiratory rate and volume of air inspired per breath are fixed, although during natural breathing these parameters vary appreciably. A computer-controlled ventilator has now been introduced that can use noise to mimic this variability. We describe a conceptual model of lung injury in which the partial pressure of arterial oxygen is improved significantly by computer-controlled rather than conventional mechanical ventilation, in agreement with recent experimental data.

Mapping the cytoskeletal prestress

Cell mechanical properties on a whole cell basis have been widely studied, whereas local intracellular variations have been less well characterized and are poorly understood. To fill this gap, here we provide detailed intracellular maps of regional cytoskeleton (CSK) stiffness, loss tangent, and rate of structural rearrangements, as well as their relationships to the underlying regional F-actin density and the local cytoskeletal prestress. In the human airway smooth muscle cell, we used micropatterning to minimize geometric variation. We measured the local cell stiffness and loss tangent with optical magnetic twisting cytometry and the local rate of CSK remodeling with spontaneous displacements of a CSK-bound bead. We also measured traction distributions with traction microscopy and cell geometry with atomic force microscopy. On the basis of these experimental observations, we used finite element methods to map for the first time the regional distribution of intracellular prestress. Compared with the cell center or edges, cell corners were systematically stiffer and more fluidlike and supported higher traction forces, and at the same time had slower remodeling dynamics. Local remodeling dynamics had a close inverse relationship with local cell stiffness. The principal finding, however, is that systematic regional variations of CSK stiffness correlated only poorly with regional F-actin density but strongly and linearly with the regional prestress. Taken together, these findings in the intact cell comprise the most comprehensive characterization to date of regional variations of cytoskeletal mechanical properties and their determinants.

Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells

The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40–100 nm and less than 44 μm) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 μm), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 μM did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.

Variation of mechanical properties and quantitative proteomics of VSMC along the arterial tree

Vascular smooth muscle cells (VSMCs) are thought to assume a quiescent and homogeneous mechanical behavior after arterial tree development phase. However, VSMCs are known to be molecularly heterogeneous in other aspects and their mechanics may play a role in pathological situations. Our aim was to evaluate VSMCs from different arterial beds in terms of mechanics and proteomics, as well as investigate factors that may influence this phenotype. VSMCs obtained from seven arteries were studied using optical magnetic twisting cytometry (both in static state and after stretching) and shotgun proteomics. VSMC mechanical data were correlated with anatomical parameters and ultrastructural images of their vessels of origin. Femoral, renal, abdominal aorta, carotid, mammary, and thoracic aorta exhibited descending order of stiffness (G, P < 0.001). VSMC mechanical data correlated with the vessel percentage of elastin and amount of surrounding extracellular matrix (ECM), which decreased with the distance from the heart. After 48 h of stretching simulating regional blood flow of elastic arteries, VSMCs exhibited a reduction in basal rigidity. VSMCs from the thoracic aorta expressed a significantly higher amount of proteins related to cytoskeleton structure and organization vs. VSMCs from the femoral artery. VSMCs are heterogeneous in terms of mechanical properties and expression/organization of cytoskeleton proteins along the arterial tree. The mechanical phenotype correlates with the composition of ECM and can be modulated by cyclic stretching imposed on VSMCs by blood flow circumferential stress.

FLUCTUATIONS, NOISE AND SCALING IN THE CARDIO-PULMONARY SYSTEM

The structure and the functioning of cardio-pulmonary system is complex and statistical physics appear to be suitable for their characterization. In this review, we examine scaling in cardio-pulmonary physiology. The focus will be on the interpretation of scaling behaviors and their relation to structure-function in the normal and diseased cardio-pulmonary system. First, we overview fluctuations and scaling in respiratory rate variability in terms of a neural network model. Next, we analyze fluctuations in human heartbeat dynamics under healthy and pathologic conditions using wavelets and multifractal approaches. We then discuss avalanche behavior of airway openings as well as scaling behavior of crackling sound generated during the process of airway openings. We also examine the relationship between the observed scaling properties and the design features of the pulmonary vascular tree. Finally, we show how the network failure of lung tissue structure leads to emphysema, a leading cause of respiratory dis...

Self-organization in growth of branched polymers

We propose a growth mechanism for branched polymers where self-organization leads the system to criticality. By incorporating a dynamical rule which simply regulates the flux of monomers available for aggregation, the system is spontaneously driven to the critical branching probability which separates the finite from infinite growth regimes. The fact that the system reaches and maintains itself close to a critical state without the need of a fine tuning of the parameters is thus discussed in terms of the self-organized criticality (SOC) concept. Finally, we also demonstrate the feasibility of the method in association with a practical implementation of the theoretical model.

Cardiac Mechanics Evaluated by Speckle Tracking Echocardiography

Natural myocardial markers, or speckles, originated from constructive and destructive interference of ultrasound in the tissues may provide early diagnosis of myocardial changes and be used in the prediction of some cardiac events. Due to its relatively temporal stability, speckles can be tracked by dedicated software along the cardiac cycle, enabling the analysis of the systolic and diastolic function. They are identified by either conventional 2D grey scale and by 3D echo, conferring independence of the insonation angle, thus allowing assessment of cardiac mechanics in the three spatial planes: longitudinal, circumferential, and radial. The purposes of the present paper are: to discuss the role and the meaning of cardiac strain obtained by speckle tracking during the evaluation of cardiac physiology and to discuss clinical applications of this novel echocardiographic technology.

Effects of Oropharyngeal Exercises on Snoring: A Randomized Trial

BACKGROUND Snoring is extremely common in the general population and may indicate OSA. However, snoring is not objectively measured during polysomnography, and no standard treatment is available for primary snoring or when snoring is associated with mild forms of OSA. This study determined the effects of oropharyngeal exercises on snoring in minimally symptomatic patients with a primary complaint of snoring and diagnosis of primary snoring or mild to moderate OSA. METHODS Patients were randomized for 3 months of treatment with nasal dilator strips plus respiratory exercises (control) or daily oropharyngeal exercises (therapy). Patients were evaluated at study entry and end by sleep questionnaires (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index) and full polysomnography with objective measurements of snoring. RESULTS We studied 39 patients (age, 46 ± 13 years; BMI, 28.2 ± 3.1 kg/m2; apnea-hypopnea index (AHI), 15.3 ± 9.3 events/h; Epworth Sleepiness Scale, 9.2 ± 4.9; Pittsburgh Sleep Quality Index, 6.4 ± 3.3). Control (n = 20) and therapy (n = 19) groups were similar at study entry. One patient from each group dropped out. Intention-to-treat analysis was used. No significant changes occurred in the control group. In contrast, patients randomized to therapy experienced a significant decrease in the snore index (snores > 36 dB/h), 99.5 (49.6-221.3) vs 48.2 (25.5-219.2); P = .017 and total snore index (total power of snore/h), 60.4 (21.8-220.6) vs 31.0 (10.1-146.5); P = .033. CONCLUSIONS Oropharyngeal exercises are effective in reducing objectively measured snoring and are a possible treatment of a large population suffering from snoring. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01636856; URL: www.clinicaltrials.gov.

Diesel exhaust particulates affect cell signaling, mucin profiles, and apoptosis in trachea explants of Balb/C mice

Particulate matter from diesel exhaust (DEP) has toxic properties and can activate intracellular signaling pathways and induce metabolic changes. This study was conducted to evaluate the activation of extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) and to analyze the mucin profile (acid (AB+), neutral (PAS+), or mixed (AB/PAS+) mucus) and vacuolization (V) of tracheal explants after treatment with 50 or 100 μg/mL DEP for 30 or 60 min. Western blot analyses showed small increases in ERK1/2 and JNK phosphorylation after 30 min of 100 μg/mL DEP treatment compared with the control. An increase in JNK phosphorylation was observed after 60 min of treatment with 50 μg/mL DEP compared with the control. We did not observe any change in the level of ERK1/2 phosphorylation after treatment with 50 μg/mL DEP. Other groups of tracheas were subjected to histological sectioning and stained with periodic acid‐Schiff (PAS) reagent and Alcian Blue (AB). The stained tissue sections were then subjected to morphometric analysis. The results obtained were compared using ANOVA. Treatment with 50 μg/mL DEP for 30 min or 60 min showed a significant increase (p < 0.001) in the amount of acid mucus, a reduction in neutral mucus, a significant reduction in mixed mucus, and greater vacuolization. Our results suggest that compounds found in DEPs are able to activate acid mucus production and enhance vacuolization and cell signaling pathways, which can lead to airway diseases.

Original ResearchSleep DisordersEffects of Oropharyngeal Exercises on Snoring: A Randomized Trial

BACKGROUND Snoring is extremely common in the general population and may indicate OSA. However, snoring is not objectively measured during polysomnography, and no standard treatment is available for primary snoring or when snoring is associated with mild forms of OSA. This study determined the effects of oropharyngeal exercises on snoring in minimally symptomatic patients with a primary complaint of snoring and diagnosis of primary snoring or mild to moderate OSA. METHODS Patients were randomized for 3 months of treatment with nasal dilator strips plus respiratory exercises (control) or daily oropharyngeal exercises (therapy). Patients were evaluated at study entry and end by sleep questionnaires (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index) and full polysomnography with objective measurements of snoring. RESULTS We studied 39 patients (age, 46 ± 13 years; BMI, 28.2 ± 3.1 kg/m2; apnea-hypopnea index (AHI), 15.3 ± 9.3 events/h; Epworth Sleepiness Scale, 9.2 ± 4.9; Pittsburgh Sleep Quality Index, 6.4 ± 3.3). Control (n = 20) and therapy (n = 19) groups were similar at study entry. One patient from each group dropped out. Intention-to-treat analysis was used. No significant changes occurred in the control group. In contrast, patients randomized to therapy experienced a significant decrease in the snore index (snores > 36 dB/h), 99.5 (49.6-221.3) vs 48.2 (25.5-219.2); P = .017 and total snore index (total power of snore/h), 60.4 (21.8-220.6) vs 31.0 (10.1-146.5); P = .033. CONCLUSIONS Oropharyngeal exercises are effective in reducing objectively measured snoring and are a possible treatment of a large population suffering from snoring. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01636856; URL: www.clinicaltrials.gov.