Percentage of abnormal vessel changes seen in the palpebral and bulbar conjunctiva and retina among occupationally exposed workers [14].
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Lima and Luis M. M. Custodio",authors:[null]},{id:"27",title:"RoboCup is a Stage which Impulse the Research of Basic Technology in Robot",slug:"robocup_is_a_stage_which_impulse_the_research_of_basic_technology_in_robot",signatures:"Cheng Xian-yi and Xia De-shen",authors:[null]},{id:"28",title:"A Multi-Robot System Architecture for Trajectory Control of Groups of People",slug:"a_multi-robot_system_architecture_for_trajectory_control_of_groups_of_people",signatures:"Edgar A. 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Ata and Habib Johar",authors:[null]},{id:"36",title:"Position / Force Hybrid Control of a Manipulator with a Flexible Tool Using Visual and Force Information",slug:"position___force_hybrid_control_of_a_manipulator_with_a_flexible_tool_using_visual_and_force_informa",signatures:"Jian Huang, Isao Todo and Tetsuro Yabuta",authors:[null]},{id:"37",title:"A Novel Parallel Engraving Machine Based on 6-PUS Mechanism and Related Technologies",slug:"a_novel_parallel_engraving_machine_based_on_6-pus_mechanism_and_related_technologies",signatures:"Kong Ling-fu and Zhang Shi-hui",authors:[null]},{id:"38",title:"Pose Estimating the Human Arm Using Kinematics and the Sequential Monte Carlo Framework",slug:"pose_estimating_the_human_arm_using_kinematics_and_the_sequential_monte_carlo_framework",signatures:"Thomas Moeslund",authors:[null]},{id:"39",title:"Cartesian Impedance Control of Flexible Joint Robots: A Decoupling Approach",slug:"cartesian_impedance_control_of_flexible_joint_robots__a_decoupling_approach",signatures:"Christian Ott, Alin Albu Schaffer, Andreas Kugi and Gerd Hirzinger",authors:[null]},{id:"40",title:"Collision-Free Path Planning in Robot Cells Using Virtual 3D Collision Sensors",slug:"collision-free_path_planning_in_robot_cells_using_virtual_3d_collision_sensors",signatures:"Tomislav Reichenbach and Zdenko Kovacic",authors:[null]},{id:"41",title:"Exploring Open-Ended Design Space of Mechatronic Systems",slug:"exploring_open-ended_design_space_of_mechatronic_systems",signatures:"Zhun Fan, Jiachuan Wang and Erik Goodman",authors:[null]},{id:"42",title:"Online Identification for the Automated Threaded Fastening Using GUI Format",slug:"online_identification_for_the_automated_threaded_fastening_using_gui_format",signatures:"Nicola Ivan Giannoccaro and Mongkorn Klingajay",authors:[null]},{id:"43",title:"Multilevel Intelligent Control of Mechatronical Technological Systems",slug:"multilevel_intelligent_control_of_mechatronical_technological_systems",signatures:"Tugengold Andrei Kirillovich, Ryzhkin Anatoliy Andreevich, Lukianov Evjeny Anatolievich and Wojciechowicz Boleslav",authors:[null]},{id:"44",title:"A Robot System for High Quality Belt Grinding and Polishing Processes",slug:"a_robot_system_for_high_quality_belt_grinding_and_polishing_processes",signatures:"Bernd Kuhlenkoetter and Xiang Zhang",authors:[null]},{id:"45",title:"Reconfigurable Mechatronic Robotic Plug-and-Play Controller",slug:"reconfigurable_mechatronic_robotic_plug-and-play_controller",signatures:"Johan Potgieter, Jonathan Zyzalo and Olaf Diegel",authors:[null]}]}]},onlineFirst:{chapter:{type:"chapter",id:"64982",title:"Acoustics and Biological Structures",doi:"10.5772/intechopen.82761",slug:"acoustics-and-biological-structures",body:'\nAirborne pressure waves are ubiquitous in all human environments and have played vital roles in the survival, evolution, and development of the human species. Under certain conditions, airborne pressure waves can be perceived as “sound” by the human auditory system. Under other conditions, they may be perceived as a whole-body or partial-body vibration. Some airborne pressure waves are not consciously perceived at all. As human societies developed and became more technological, airborne pressure waves emanating from human-made devices became ubiquitous and “noise” became a more serious issue. By the late nineteenth century, noise and health studies began to flourish. In the early twentieth century, the telephone and growing industrialization led to more in-depth studies of the human hearing function. In 2011, a WHO document on the burden of diseases reflected the seriousness of the ongoing “noise problem” [1].
\nThe only airborne pressure waves considered of consequence for human health were those that could be
Acoustical spectrum showing the classical three segments (infrasound, audible, and ultrasound) with the frequency and wavelength indicated at the cutoff of each segment.
Figure 2 shows the frequency response curve for the dBA metric, clearly following the human auditory response to airborne acoustic pressure waves.
\nFrequency response curve for the deciBel-A metric (dBA) commonly used in noise-related legislation [
While the dBA metric proved to be key for the protection of hearing and speech intelligibility, it was insufficient for the assessment of airborne pressure waves occurring outside of the 800–7000 Hz range. Figure 3 emphasizes the 800–7000 Hz range within the dBA metric, and Figure 4 shows its application at 10 Hz. The dBA metric is, therefore, unsuited for evaluating airborne pressure waves occurring at frequencies below 800 Hz. Health effects that may be developing due to exposures at these lower frequencies cannot be properly studied if the dBA metric is being used to characterize acoustical environments.
\nFrequency response curve for the dBA metric applied to the range of highest human auditory acuity. Within this frequency range, the dBA measurement will accurately reflect the airborne acoustical energy present in the environment.
Frequency response curve for the dBA metric applied to infrasonic frequency ranges, showing a 70 dB difference when evaluated at 10 Hz. Within these lower frequency ranges, the dBA metric will significantly underestimate the airborne acoustical energy present in the environment.
There is a shortage of studies that properly evaluate the biological response to infrasonic (≤20 Hz) or lower frequency (≤200 Hz) airborne pressure waves. Three important reasons for this have been provided above: the rudimentary segmentation of the entire acoustical spectrum into merely three “blocks” (compare to segmentation of the electromagnetic spectrum), the unsuitability of the dBA metric to quantify airborne acoustical pressure waves at these lower frequencies, and the ingrained notion that “what you can’t hear can’t hurt you.” These major hindrances have been crystallized into mainstream science [3] and have served to significantly impede scientific inquiry and human health protection.
\nThe goal of this chapter is to consolidate what is known on the biological response to airborne pressure waves occurring within the infrasonic and lower frequency ranges. A biomedical engineering approach is taken, whereby biological organisms are viewed as structures of composite materials, with significant viscoelastic components and organized in accordance with the principles of tensegrity architectures. When airborne pressure waves impact these types of structures, the biological response will depend on the type of biomaterial under study, it will exhibit anisotropic properties, and it will vary nonlinearly with exposure time. Depending on the physical properties of the airborne pressure waves (including time profiles) and on the biostructure under study, mechanical perturbations are relayed into cells and tissues through a variety of different pathways that, to date, still remain unclear.
\nViscoelasticity is an attribute given to bodies that exhibit both viscous and elastic behaviors beyond the classical Hooke’s elastic model [4]. Viscoelastic materials have three distinct properties not contemplated by Hookean models: creep, stress relaxation, and hysteresis. Most biological materials have viscoelastic behaviors.
\nIn a Hookean (or purely elastic) material, total deformation depends on total load, and no further deformation occurs even if load is maintained. In viscoelastic materials, however, when sufficient stress is applied and maintained, they may continue to deform, even though stress load remains unaltered. This property is called
In a purely elastic material, the strain within the material is constant throughout the application of the load; it does not vary with time, but only with the amount of applied stress. In viscoelastic materials, when stress is applied and maintained, strain can decrease with time. This property is called
Consider repetitive or cyclical loads on materials. In purely elastic materials, periodic loads will not alter the stress-strain curve. The pathway taken by the material to deform is exactly the same pathway it takes to return to its original, equilibrium position. In viscoelastic materials, however, the return to equilibrium may be different than the pathway used to get to the point of deformation (The word pathway is here loosely used, and is meant to encompass all spatial, temporal and energetic components of these types of movements.) This property is called
Many structures in the natural world are organized in accordance with the principles of tensegrity architecture—elements providing discontinuous compression are held together through elements of continuous tension [5]. Figure 5 shows several examples of tensegrity structures.
\nTensegrity structures. A. Model showing elements of continuous tension and discontinuous compression. B. Needle tower, by Kenneth Snelson, in the Hirshhorn sculpture garden (USA) [
Depending on the properties of the airborne pressure waves and biomaterial under study, the propagation of mechanical perturbations throughout these types of structures can reach long distances, without loss of structural integrity.
\nCells and tissues are organized in accordance with the principles of tensegrity architecture [8, 9]. This means that in addition to biochemical signaling, cells also communicate with their surroundings through mechanical signals. Mechanosensitive receptors exist on cell surfaces, and mechanosensitive junctions interconnect cells, thus forming tissues. Depending on the physical properties of the airborne pressure waves and biomaterials under study, external airborne mechanical perturbations can elicit a mechanical response, which, in a larger, macroscopic view, can lead to clinically pathological situations.
\nThe fascia is a sheet of connective tissue that uninterruptedly extends from head to toe, suspended from the skeleton, and that provides the integrated supporting framework for maintaining anatomical and structural form [10, 11]. That external mechanical perturbations elicit responses at large distances away from the point of entry is a well-known concept among scientists and health professionals who study fasciae. When presented with external airborne pressure waves, fasciae can respond by changing their structural properties:
Connective tissue structures are ubiquitous forming all external surfaces of vessels, nerves, organs, and muscles, and at the cellular level, the extra-cellular matrix that surrounds and communicates with each individual cell. In addition to maintaining structural integrity, the fasciae are the first line of defense against external perturbations, playing important physiological roles in mobilizing the immune system.
\nStudying the effects of infrasonic or lower-frequency airborne pressure waves on biological structures is a very complex undertaking, whether it be on cell cultures, on animal models, or on human populations. Laboratorial studies, occupational field studies, and residential field studies all have their own strengths and weaknesses. When the latter go unrecognized, however, experimental design flaws can ensue. In this section, the attributes of these different experimental setups are discussed, and their weaknesses and strengths are explored. Together with the preceding section, this serves as a preamble to Section 4, where the results of experimental studies are described in detail.
\nLaboratories where infrasonic and lower frequency airborne pressure waves can be applied in a controlled manner are in short supply worldwide, and those that do exist are mostly associated with military installations. Laboratories emitting airborne pressure waves with infrasonic and lower frequency components cannot be randomly placed within residential environments; issues with neighbor disturbance and public health would curtail its use. Moreover, the equipment used to generate the airborne pressure waves is, typically, very large and very expensive, and few sectors of society (other than military or space exploration industries) would have the need for an extensive use of these types of installations.
\nIn these laboratory settings, continuous or pulsed-trains of single-tone airborne pressure waves can be applied, as well as, broadband exposures that can be accurately characterized. The fact that exposure times and acoustic parameters can be precisely controlled is one of the strengths of laboratorial studies, allowing for continuous time exposures, or occupationally simulated exposure schedules. Immediate (hours or days) versus long-term (weeks or months) effects can also be explored.
\nThere are numerous types of biological outcomes that can be studied under laboratorial conditions. Light-, electron- and atomic-force microscopy can be used to study cellular and tissue structural properties, as well as their chemical composition and content of bio-reactive elements. Polymerase chain reaction (PCR) techniques can provide information on messenger RNA (mRNA) expression, allowing for the identification of key pathways. With pharmacological intervention or gene knock-out specimens, specific signaling molecules and pathways involved in the elicited responses can be pinpointed. Additionally, control populations for comparison are fairly easy to achieve—they are simply not subjected to the laboratorial exposures.
\nOccupational environments are exceptional field laboratories, as both short-term (several months) and long-term (years) effects can be investigated in more realistic acoustic environments. Typically, different workstations have different acoustical features that can greatly depend on different machinery regimens. For occupational field laboratories, acoustical characterizations of the workplace(s) must be comprehensively undertaken and time exposures to each type of environment should be scored.
\nExposure times at work must be differentiated from exposure times away from work, i.e., when the work shift ends, workers leave the field laboratory, but additional exposures to infrasonic or lower frequency airborne pressure waves may be incurred (e.g., recreational, transportation). These must be documented. Significant confounding factors may be introduced unless each subject’s residential area is scrutinized and prior-exposure histories probed for fetal, childhood, and adolescent exposures.
\nPossible biological outcomes within occupational field studies are more limited when compared to laboratory exposures. Noninvasive testing can be imprecise, and the minimally invasive testing (such as a blood chemistry analysis, X-ray, or MRI) may also not be sufficiently precise to yield relevant data. It is also the case that scientific knowledge on relevant biological outcomes that can be noninvasively evaluated in exposed humans is still absent or, at best, very incomplete.
\nSurvivorship bias is a well-known confounding factor in human population studies. In occupational environments, workers with more time on-the-job are those who have survived throughout the years of professional activity, while workers with less time in professional activity may exhibit more severe biological outcomes. This phenomenon is often misinterpreted leading to inconclusive or erroneous conclusions.
\nControl populations for exposures to infrasonic and lower frequency airborne pressure waves have been a very difficult proposition, given the ubiquitous nature of this stressor. One of the solutions to this profound problem is the scoring of subjects into different groups as per their exposure. Within this context, control groups are composed of individuals who have the least amount of cumulative (prior and present) exposure, and not of individuals with zero exposure.
\nDifferent professions can provide different field laboratories, both in terms of acoustic environment and time exposure schedules. For example, long-haul truck drivers are typically exposed for more than 8 hours daily and, oftentimes, sleep in the truck while it is idling, or while refrigeration systems are continuously operating. Workers onboard ships, submarines, offshore oilrigs, aircraft, and spacecraft (for example) can be exposed to significant amounts of infrasonic and lower frequency airborne pressure waves for weeks or months at a time. The wealth of information waiting to be gleaned from these types of field laboratories is breathtaking.
\nField laboratories in urban, suburban, and rural residential settings are generally designed to investigate environmental health effects due to human-made infrasonic and lower frequency airborne pressure waves. Typically, these sources are associated with industrial complexes or infrastructure that, in turn, are usually linked with important economic interests. In general, the amount and type of infrasonic and lower frequency airborne pressure waves contaminating a home will depend on the machine operation and/or the use of the infrastructure. For example, in most urban and suburban areas, airports must close down between the hours of midnight and 5 am. Some factories do not have night shifts and therefore also have daily shutdown periods. Large refrigeration units, hydroelectric dams, and large volume highways, however, must be kept running 24/7 and can also be viewed as continuous sources of infrasonic and lower frequency airborne pressure waves. Wind turbines are the latest addition to these type of sources although they are almost exclusively within rural areas.
\nComprehensive characterization of the acoustic environments in the different residential areas must be undertaken (e.g., master bedroom, children’s bedrooms, living-lounge areas), since room-resonance phenomena can significantly modify the acoustic environment that is originally being induced and driven by external, incoming airborne pressure waves. Additionally, wind can also influence the spectrum, intensity and type of infrasonic and lower frequency airborne pressure waves that exist within a room. This differentiation is readily achieved with proper acoustic evaluations.
\nResidential exposure times are much more difficult to control, as they can differ from room to room and on an hourly basis. Moreover, subjects may also be sleeping within the “contaminated” environments, which can severely aggravate biological outcomes. If exposure is concomitantly occurring during sleep and waking hours (e.g., homemakers, workers from home, farmers), then biological outcomes may be further aggravated. Leaving the home can be equated with a biological recovery period (i.e., nonexposure period).
\nShort-, medium- and long-term effects can be studied in residential settings when the implementation of a new infrastructure or industrial complex is known to be coming to the area. Biological outcomes should strive to be either noninvasive or minimally invasive, and prior-exposure histories are fundamental for achieving useful statistical data.
\nNumerous studies conducted over the decades have shed light on the biological response to infrasonic and lower frequency airborne pressure waves and associated symptomatic complaints. Due to space limitations, this discussion will only deal with some of the vascular and collagenous abnormalities, cardiomyocyte changes, and the hippocampus responses, as induced by different types of exposures. For reasons explained in the section “Introduction,” all studies using the dBA metric have been eliminated from consideration (with one exception in an occupational setting). Selected studies mostly focus on the cellular and tissue changes observed in laboratory, occupational, and residential settings, using light and electron microscopy. The sequence in which the studies are presented does not follow the classical anatomical order.
\nIn the mid-1960s, within a military setting, the immediate exposure to 10–60 Hz, at 118–140 dB, for 2 minutes, induced disturbances of the visual field as reported by all five human subjects [12]. In 1985, laboratorial animal studies exposed rats to tonal 8 Hz at 100–140 dB, 3 hours daily, for 5, 10, 15, or 25 days, and examined the blood and lymph networks of the palpebral (eyelid) and bulbar (eye globe) conjunctiva.
In a similar study, animals were exposed to 8 Hz at 100 dB, or to 16 Hz at 100 dB, 3 hours daily, for 1 month. Clinical and morphological evaluations were conducted at days 3, 7, 15, 30, and also post-exposure at days 30, 60, and 90.
Within an occupational setting (reinforced concrete factory), vessel changes in the palpebral and bulbar conjunctiva, and in the retina, were investigated among 214 workers (age range: 20–58 years), with 1–30 years of employment. Workers were divided into two groups:
The exposed group was divided into subgroups as per years of professional activity. Table 1 describes each subgroup and the vessel abnormalities found. No such abnormalities were found in the control population [14].
\nOccupational exposure time | \n1–2 yrs | \n3–10 yrs | \n11–20 yrs | \n20–30 yrs | \n
---|---|---|---|---|
Number of workers | \n21 | \n84 | \n36 | \n19 | \n
Palpebral and bulbar arteries (%) | \n||||
0 | \n82 | \n8 | \n0 | \n|
0 | \n17 | \n91 | \n100 | \n|
0 | \n80 | \n100 | \n100 | \n|
Retinal arteries (%) | \n||||
0 | \n0 | \n0 | \n0 | \n|
0 | \n91 | \n100 | \n100 | \n|
0 | \n90 | \n100 | \n100 | \n|
Retinal veins (%) | \n||||
0 | \n87 | \n11 | \n0 | \n|
0 | \n13 | \n88 | \n100 | \n|
0 | \n75 | \n97 | \n100 | \n
Percentage of abnormal vessel changes seen in the palpebral and bulbar conjunctiva and retina among occupationally exposed workers [14].
Within a different occupational setting (aircraft industry), ocular changes were studied in 23 male workers (average age: 42, range: 32–58 years). Lesions were observed in the blood-retinal barrier in 19 workers (lesion types: 13 inactive, 2 active, 4 mixed). Choroidal circulation was altered in 14 workers (late perfusion with chronic features). Changes in retinal circulation were observed in four workers (type: 1 occlusive, 1 exudative, 2 mixed). Three workers presented with optic neuropathy (1 papillitis, 2 optic atrophy), and one exhibited sensorial retinal macular detachment [15]. The immediate effects of tonal exposures with 8 Hz at 130 dB, 2 hours daily, for 1, 7, 14 and 21 days, also revealed a breakdown of the blood-retinal barrier in the rat eye [16].
\nThese studies strongly suggest that under the impact of infrasonic and lower frequency airborne pressure waves, a vascular response is mounted by ocular structures and could be related to decreased visual acuity in workers. Data in Table 1 seem to indicate that, as exposure time progressed, vessels that were initially enlarged ceased to exist, apparently being replaced with narrower and twisted vessels. Enlarged vessels usually suggest the need for an increased blood supply. However, given the sustained mechanical insult, making the vessels narrower and twisting them throughout the structures may, in fact, reflect a more efficient blood delivery system.
\nThis concept is further reinforced by the observation of narrow and twisted blood vessels in the gastric mucosa of rats, exposed to non-tonal, occupationally simulated (aircraft industry) acoustic environments characterized as 6.3–25 Hz at 70–90 dB and 40–500 Hz at 90–100 dB. Continuous exposure was applied, and evaluations occurred at 1, 3, 5, 9, and 13 weeks. In
Vascular changes were also identified in the liver structures of animals exposed to 2, 4, 8, or 16 Hz, at 90–140 dB, 3 hours daily, for 5–40 days. Exposures to 2 or 4 Hz induced less damage than exposures to 8 and 16 Hz.
Hemorrhagic events in the lung were documented as early as 1969, within the Soviet and US space exploration studies, in dogs exposed to occupationally simulated (spaceflight) wide-band frequency range at 105–155 dB, for 1.5 or 2 hours. Hemorrhages up to 3 mm in diameter were observed beneath the pleura. As exposure time and decibel level increased, the number of hemorrhages increased but never exceeded 3 mm in diameter. Microscopic analyses of the hemorrhagic sections disclosed ruptured capillaries and larger blood vessels [22]. In a laboratory setting, rats received tonal exposures to 2, 4, 8, or 16 Hz at 90–140 dB, 3 hours daily, for 40 days. Analysis time points were conducted after 3 hours, at 5, 10, 15, 24, and 40 days of exposure, as well as during post-exposure times.
The highly invasive bronchoscopic evaluation with biopsy was performed among a group of volunteer subjects, with occupational or residential exposures to infrasonic and lower frequency airborne pressure waves, as detailed in Table 2.
\nProfession/type of exposure | \nGender | \nAge | \nSmoking | \n
---|---|---|---|
Aircraft technician | \nMale | \n48 | \nMild | \n
Aircraft technician | \nMale | \n52 | \nNo | \n
Aircraft technician | \nMale | \n59 | \nMild | \n
Combat pilot | \nMale | \n61 | \nNo | \n
Helicopter pilot | \nMale | \n59 | \nModerate | \n
Aircraft pilot | \nMale | \n54 | \nNo | \n
Merchant marine | \nMale | \n37 | \nNo | \n
Military helicopter nurse | \nFemale | \n56 | \nNo | \n
Flight attendant | \nFemale | \n36 | \nNo | \n
Flight attendant | \nFemale | \n39 | \nNo | \n
Flight attendant | \nFemale | \n40 | \nNo | \n
Homemaker | \nFemale | \n54 | \nMild | \n
Homemaker | \nFemale | \n59 | \nNo | \n
Description of subjects who received bronchoscopic evaluations with biopsy [24].
Bronchoscopic observations in all patients revealed small submucosal, vascular-like lesions (“pink” lesions), located distally in both tracheal and bronchial trees, and uniformly distributed bilaterally near the spurs. Biopsies were performed on the abnormal mucosa (pink lesions) and on the apparently normal mucosa (outside of the pink lesions). In the non-pink areas, some vessel wall thickening was visible. In the pink areas, the basal membrane disclosed abnormal neovascularization, with thickened blood vessel walls and scarce lumen. No gender differences were identified [24].
\nCollagen, composed of triple-helix tropocollagen chains, is the most abundant protein in the human body, a key component of the fasciae, and is produced by fibroblast cells. It has long since been considered as the “steel” of the human body [25], but its energy storage capacity has been shown to be 10 orders higher than in spring steel [26]. Different types of collagen have different mechanical properties. Type IV collagen (increased in the exposed gastric mucosa [17]—see above), is organized into X-shaped structures and is commonly found in the basal membrane of arterial walls, hence its increased expression during angiogenesis.
\nIn
In the lungs of dogs studied within the scope of space exploration (see above [22]), focal enlargement of the alveoli involved the stretching of connective tissue structures of alveoli walls. In the biopsy images of the bronchoscopic study (see above [24]), non-pink areas disclosed a thickened basement membrane with abnormal amounts of collagen, while the pink areas disclosed an even thicker membrane with very large amounts of collagen. The abnormal neovascularization was embedded within collagen bundles. Retraction of structures neighboring the collagen fibers was not observed. A marked reinforcement of the cytoskeleton and intercellular junctions was seen in the pink areas, as compared to non-pink areas. The five individuals that disclosed images of collagen fiber degeneration and disruption also tested positive for antinuclear antibodies.
\nUnder an occupationally simulated acoustic environment, characterized as 20–200 Hz at 70–90 dB (aircraft industry), and occupationally simulated exposure schedules (8 hours daily, 5 days weekly, weekends in silence), focal interstitial fibrosis was found in the lung parenchyma of rats after a cumulative 4000-hour exposure. Additionally, thickened alveoli walls and dilated alveoli were observed [27]. Tracheal epithelium in similarly exposed rats disclosed significant subepithelial fibrosis [28, 29], and with longer occupationally simulated exposures, the subepithelial layer became composed of hyperplastic collagen bundles, some with a degenerative pattern. Cellular edema was also observed [28, 30].
\nWithin an occupational setting (aircraft industry) and investigating long-term outcomes, high-resolution CT scans of the lungs and respiratory function tests were provided to 21 nonsmoker male workers, who were divided into two groups: with (n = 7, average age: 42) and without (n = 15, average age: 36) complaints of airflow limitations. There was a significant relationship between the presence of symptoms and images of lung fibrosis through the CT scan. No differences existed among the groups when comparing the percentage of predicted values of lung function [31].
\nFasciae abnormalities have been most prominently studied in the pericardia of exposed workers, subsequent to autopsy findings in an aircraft industry worker that disclosed a grossly thickened pericardium [32]. Pericardial morphological changes were studied among 12 male workers: three aircraft technicians, four fixed-wing aircraft pilots, four helicopter pilots, and one long-haul truck driver. Pericardial samples were removed with informed consent of the patient and Ethics Committee approval, at the beginning of cardiac surgery (prescribed for other reasons by the National Healthcare Service). In all cases, there were no visual adherences, or inflammatory aspects and pericardia were grossly thickened. The classical, three pericardial layers were identified: serosa, fibrosa, and epipericardium. However, in all cases, the fibrosa had split in two and, in between, a new layer of loose tissue was observed, consisting of vessels, nerves, arteries, and lymphatics surrounded by adipose tissue. Both fibrosa layers were composed almost entirely by wavy, interwoven collagen bundles, surrounded by numerous cytoplasmic extensions (whose mother cell was difficult to identify), and interspersed with some elastic fibers. The new, loose tissue layer sandwiched in between the split fibrosa contained blood and lymphatic vessels, adipose tissue, and nerves. Both the loose tissue layer and the fibrosa layers contained macrophages and vascular hyperplasia, also seen in lymphatic vessels [33, 34, 35, 36]. Pericardial and cardiac valve thickening has also been confirmed through echocardiography studies in occupational settings (aircraft [37] and commercial-airline industries [38]), with thickness increasing with increasing exposure time. In residential settings, pericardial and valve thickening [39] and increased arterial stiffness [40] were observed in populations chronically exposed to military-training exercises [39], and transportation systems [40].
\nIn 1983, electron microscopy techniques were used to study animal myocardia exposed to single and multiple infrasonic exposures of 4–16 Hz at 90–150 dB, 3 hours daily, for 45 days, and post-exposure time points were included. No changes were observed with single exposures at 4–6 Hz and at less than 100 dB, when compared to non-exposed controls.
Cardiac injury was studied in rat cardiomyocytes exposed to tonal 5 Hz at 130 dB, 2 hours daily, for 1, 7, or 14 days.
For three continuous months, rats were exposed to non-tonal, occupationally simulated (aircraft industry) acoustical environments characterized as 6.3–25 Hz at 70–90 dB and 40–500 Hz at 90–100 dB. Ventricular cardiac muscle and interstitial fibrosis were quantified and compared to non-exposed controls. Exposed rats disclosed a 97.5% increase in fibrosis in the left ventricle, an 81.5% increase in the interventricular septum, and an 83.7% increase in the right ventricle. No significant differences were found in the mean values of cardiac muscle in the left and right ventricles, when compared to non-exposed controls. However, the fibrosis-to-muscle ratio was significantly higher in the exposed rats, indicating significant ventricular myocardial fibrosis [44].
\nIn another study, rats were exposed to a non-tonal, occupationally simulated (textile mill) environment rich in infrasonic and lower frequency components, under an occupationally simulated schedule (8 hours daily, 5 days weekly, weekends in silence), for 1, 3, 5, and 7 months. Ventricular coronary artery caliber, artery wall thickness, and size of arterial perivascular tissue were quantified in a total of 130 arteries (61 exposed and 69 controls). No changes were observed in arterial lumen caliber, and in arterial wall thickness, when compared to non-exposed controls. Perivascular tissue was more prominent in the exposed samples and seemed to exhibit fibrotic development. Lumen-to-wall ratio showed no differences, while wall-to-perivascular-tissue ratio showed a significant increase, as compared to non-exposed controls [45].
\nIn animals exposed to 2–20 Hz peaking at 114 dB, for 28 continuous days, ventricular arteries were studied as to the dimensions of lumen, wall, and perivascular space. An additional group of animals received the same exposure but were treated with dexamethasone (a corticosteroid). Blind evaluation of 31 arteries disclosed increased perivascular spaces in the exposed groups, reflected in the significantly reduced wall-to-perivascular-space ratio, as compared to non-exposed controls. No changes were observed in the lumen-to-wall ratio. With dexamethasone treatment and exposure, no differences were observed in the wall-to-perivascular-space ratio, as compared to controls, suggesting an underlying inflammatory mechanism [46].
\nGap junctions are a fundamental component of intercellular communication, allowing inorganic ions and small water-soluble molecules to pass directly from one cell’s cytoplasm to another. Gap junctions are formed by protein complexes (connexons) each composed of six subunits made of the protein connexin. Cardiac connexin43 (Cx43) is a component of gap junctions, and its reduction in combination with increased collagen deposition and interstitial fibrosis has been associated with ventricular arrhythmias [47]. Within this context, rats were exposed to non-tonal, occupationally simulated (aircraft industry) acoustical environments characterized by 6.3–25 Hz at 70–90 dB and 40–500 Hz at 90–100 dB, for three continuous months. Immunohistochemical quantification of Cx43 was conducted on the left ventricle, interventricular septum, and right ventricle. Significantly decreased Cx43-to-muscle ratios were found in the exposed rats, as compared to non-exposed controls, suggesting the possibility of arrhythmogenic consequences [48].
\nPrior studies have shown that the hippocampus is involved in learning and memory impairment, such as that seen in rodents after infrasound exposure [49]. The hippocampus—located between the cerebral hemispheres and the brainstem—was classically considered as part of the limbic system. The hippocampus proper is divided into four regions (CA1, CA2, CA3, and CA4), each with different input and output pathways. The Dentate Gyrus (DG) is an additional hippocampus structure and that contributes to the formation of new episodic memories, and spontaneous exploration of novel environments. In the central nervous system (CNS), neuroglia consists of the non-neuronal cells (oligodendrocytes, astrocytes, ependymal cells, and microglia) and is often referred to as the connective tissue of the brain. Glial cells surround neurons to hold them in place, supply them with oxygen and nutrients, insulate them from one another, destroy pathogens, and remove dead neurons.
\nGlial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed by numerous cells within the CNS, and although its exact function remains unknown, it appears to be involved in maintaining the mechanical strength of astrocytes. The expression of GFAP was studied in the brains of mice exposed to 16 Hz at 130 dB, 2 hours daily, for 1, 7, 14 21, or 28 days. GFAP expression was increased in the hippocampus, cortex, and hypothalamus in a time-dependent manner [50].
\nCorticotrophin releasing hormone (CHR) is a peptide hormone involved in the stimulation of the pituitary synthesis of ACTH (adrenocorticotropic hormone) as part of the hypothalamic-pituitary-adrenal axis’ response to stress. Corticotrophin releasing hormone-receptor 1 (CHR-R1) has wide expression in the CNS. It plays important roles in fear learning and consolidation in the amygdala, in stress-related modulation of memory function in the hippocampus, and in arousal regulation in the brainstem. Prior studies showed that infrasound exposures caused an upregulation of CRH and CRH-R1 in neurons of the hypothalamic paraventricular nucleus [51]. Recent studies have also shown that CRH is expressed in activated microglial cells [52]. Within this context, rats and
The transient receptor potential cation channel, subfamily V, member 4 (TRPV4) protein acts as a calcium channel that is also mechanosensitive. It plays important roles in the systemic regulation of osmotic pressure by the brain, in skeletal growth and structural integrity, in airway and lung function, retinal and inner ear function, and in pain. Animals were exposed to 8 or 16 Hz at 90, 100 or 130 dB, 2 hours daily, for 14 days. Rat learning and memory abilities were most severely impaired with 16 Hz at 130 dB at days 7 and 14, with prominent loss of hippocampal CA1 neurons, as compared to non-exposed controls. Significant astrocyte and microglial activation was seen in the hippocampus after days 1 and 7, and before neuronal apoptosis became evident.
Neonatal rat hippocampal astrocyte cultures were exposed to 16 Hz at 130 dB for 15, 30, 60, 90, 120, and 240 minutes. Extra-cellular glutamate levels increased with increasing exposure time, and at 90 min, there was a 100% increase over baseline. The astroglial expression of Cx43 (connexin43—see above) was increased, as compared to non-exposed controls, as was the synthesis of Cx43 mRNA. Through additional evaluations using pharmacological and knock-out interventions, the authors concluded that infrasonic exposures induced astrocytes to release glutamate, and that Cx43 gap junctions were required for the exposure-induced glutamate release [54].
\nThe endocannabinoid system includes lipid-based retrograde neurotransmitters, expressed throughout the CNS, and involved in fertility, pregnancy, pre-and postnatal development, appetite, pain-sensation, mood, and memory. Animals were exposed to 16 Hz at 130 dB, 2 hours daily, for 14 days. Cannabinoid (CB) receptors 1 and 2 in the CA1 hippocampal region of the exposed rats were downregulated in a time-dependent manner, as compared to non-exposed controls. Apoptotic cells in the CA1 only became obvious after day 5, and cell death coincided with the decreased expression of CB receptors. Through pharmacological intervention, activation of CB receptors significantly reduced the number of apoptotic cells, ameliorated the behavior performance of exposed rats, and reduced the infrasound-elevated levels of proinflammatory cytokines. These data suggest that CB receptors could potentially serve as promising targets for future treatments against infrasound-induced injury [55].
\nFibroblasts synthesize extracellular matrix (glycosaminoglycans, reticular, and elastic fibers) and collagen, and, in addition to their structural role, fibroblasts are also important for mounting the immune response to tissue damage. Fibroblast growth factors (FGF) signal through fibroblast growth factor receptors (FGFR). The fibroblast growth factor 2/fibroblast growth factor receptor 1 (FGF2/FGFR1) signaling pathway was investigated in animals and in cultured astrocytes, exposed to 16 Hz at 150 dB, 2 hours daily, for 1, 3, or 7 days. In both experimental models, astrocyte activation increased with exposure time and astrocyte-expressed FGFR1 was downregulated as compared to non-exposed controls. Pharmacological intervention using FGF2 exerted an inhibitory effect on infrasound-induced astrocyte activation, inhibited the elevation of proinflammatory cytokines, upregulated the expression of FGFR1, and alleviated neuron loss in CA1 hippocampus region. Inhibition of the FGF2/FGFR1 pathway aggravated astrocyte-mediated inflammation after infrasonic exposure. The authors concluded that astrocyte-mediated inflammation was involved in infrasound-induced neuronal damage and that the FGF2/FGFR1 pathway played a key role [56].
\nIn a laboratory setting, rats were exposed to tonal 8 Hz at 140 dB, 2 hours daily, for 3 days. A post-exposure, 1-week time point was also established. Significant damage of hippocampus morphology was observed in exposed rats, and recovery was seen after 1 week of post-exposure. Neuronal apoptosis was significantly increased after 24- and 48-hour exposures, as compared to non-exposed controls, and then decreased after 1 week post-exposure. Expression of heat shock protein 70 (HSP70) peaked at 24 hours and was decreased at 48 hours [57].
\nExposure to infrasonic and lower frequency airborne pressure waves can cause cellular and tissue damage depending on frequency, dB-level, and exposure time, while the viscoelastic properties inherent to biological tissues impart a nonlinear response to this type of acoustic stressor. The complex mechanosensitive and biochemical cellular signaling pathways mediating this cellular damage have not yet been pinpointed, although fasciae structures and connective tissues (including the neuroglia) seem to be the most sensitive under longer term exposures. Immediate exposures appear to induce inflammatory processes that do not seem to be maintained with longer exposures.
\nWidespread vascular involvement (not limited to the biological structures addressed herein) was observed in palpebral and bulbar conjunctiva and retina, gastric mucosa, liver structures, lungs, pleura and tracheae, alveoli, pericardia, and coronary arteries. This vascular response may (unsuspectingly) be the underlying cause of many symptomatic complaints. Cognitive deficits oftentimes documented within residential field laboratories may not merely be due to sleep deprivation, but also to hippocampal neuronal damage. Fasciae morphogenesis speaks to the demand on the whole-body structural integrity elicited by this type of external mechanical insult, while collagenous growths and hemorrhagic events of a focal nature may reflect concomitant resonance phenomena.
\nRecovery periods are not linear, and 2-hour daily exposures imply a 22-hour nonexposure period. This presents a problem for continuous exposures, such as those encountered in some professional activities and most residential environments. The underlying objectives of most of the studies discussed herein are related to occupational exposures and do not consider continuous exposures at less than 90 dB, nor are pressure pulsed trains presented within the laboratorial acoustic environments. In residential environments, however, these attributes are often present. The simulation of residential exposures does not appear to have yet been integrated into laboratory settings and protocols.
\nThe whole-body response also elicits the immune system, affects organs of the reproductive system, changes receptor cells in the vestibular semicanals and auditory cochlea, and induces genotoxic effects, including teratogenesis. This is a pioneering field of science, still in its infancy and urgently requiring scientists from multidisciplinary areas of study because, ultimately, the health of human populations and their offspring must be protected.
\nNone.
General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed.
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\n\nRead more about Open Access in Horizon 2020 here.
\n\nWhich scientific publication to choose?
\n\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
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