Air Traffic Control Research Articles

Feasibility of contrail avoidance in a commercial flight planning system: an operational analysis

Aircraft condensation trails, also known as contrails, contribute a substantial portion of aviation’s overall climate footprint. Contrail impacts can be reduced through smart flight planning that avoids contrail-forming regions of the atmosphere. While previous studies have explored the operational impacts of contrail avoidance in simulated environments, this paper aims to characterize the feasibility and cost of contrail avoidance precisely within a commercial flight planning system. This study leverages the commercial Flightkeys 5D algorithm, developed by Flightkeys GmbH, with a prototypical contrail forecast model based on the Contrail Cirrus Prediction (CoCiP) model to simulate contrail avoidance on 49 411 flights during the first two weeks of June 2023, and 35 429 flights during the first two weeks of January 2024. The utilization of a commercial flight planning system enables high-accuracy estimates of additional cost and fuel investments by operators to achieve estimated reductions in contrail-energy forcing and overall flight global warming potential. The results show that navigational contrail avoidance will require minimal additional cost (0.08%) and fuel (0.11%) investments to achieve notable reductions in contrail climate forcing (−73.0%). This simulation provides evidence that contrail mitigation entails very low operational risks, even regarding fuel. This study aims to serve as an incentive for operators and air traffic controllers to initiate contrail mitigation testing as soon as possible and begin reducing aviation’s non- CO2 emissions.

E-Cigarette Exposure Alters Neuroinflammation Gene and Protein Expression in a Murine Model: Insights from Perinatally Exposed Offspring and Post-Birth Mothers.

The use of E-cigarettes, often considered a safer alternative to traditional smoking, has been associated with high rates of cellular toxicity, genetic alterations, and inflammation. Neuroinflammatory impacts of cigarette smoking during pregnancy have been associated with increased risks of adverse childhood health outcomes; however, it is still relatively unknown if the same propensity is conferred on offspring by maternal vaping during gestation. Results from our previous mouse inhalation studies suggest such a connection. In this earlier study, pregnant C57BL/6 mice were exposed daily to inhaled E-cig aerosols (i.e., propylene glycol and vegetable glycerin, [PG/VG]), with or without nicotine (16 mg/mL) by whole-body inhalation throughout gestation (3 h/d; 5 d/week; total ~3-week) and continuing postnatally from post-natal day (PND) 4-21. As neuroinflammation is involved in the dysregulation of glucose homeostasis and weight gain, this study aimed to explore genes associated with these pathways in 1-mo.-old offspring (equivalent in humans to 12-18 years of age). Results in the offspring demonstrated a significant increase in glucose metabolism protein levels in both treatment groups compared to filtered air controls. Gene expression analysis in the hypothalamus of 1 mo. old offspring exposed perinatally to E-cig aerosols, with and without nicotine, revealed significantly increased gene expression changes in multiple genes associated with neuroinflammation. In a second proof-of-principal parallel study employing the same experimental design, we shifted our focus to the hippocampus of the postpartum mothers. We targeted the mRNA levels of several neurotrophic factors (NTFs) indicative of neuroinflammation. While there were suggestive changes in mRNA expression in this study, levels failed to reach statistical significance. These studies highlight the need for ongoing research on E-cig-induced alterations in neuroinflammatory pathways.

Features of scientific research work of future aviation specialists

The article presents the peculiarities of research work of future aviation specialists. It is noted that higher education institutions in the aviation field pay considerable attention to ensuring the scientific and research component of the use of modern educational technologies for the professional training of future specialists. The purpose of the study was the analysis and peculiarities of the research work of aviation institutions of higher education, aimed at the formation of research skills and professional skills. The methods of research were the analysis and generalization of scientific literature on the organization of research work in higher education, ICAO documents regulating the flight safety management system for air transport. Features of research work for students of higher education at aviation institutions are singled out, in particular: application of the problem-based learning method through the analysis of aviation regulatory documents and investigation materials of aviation events; simulation of real professional situations through a business game (imitation simulation), where the student is given the opportunity to be a pilot, air traffic controller, dispatcher-instructor, aviation shift leader, etc.; student conferences as an opportunity to present professional research work; simulator (practical) training; the practically oriented character of the educational program – the involvement and use of the work experience of aviation specialists-practitioners. The criteria for ensuring the effective organization and implementation of research work of future aviation specialists are summarized, which is the complexity, consistency and comprehensiveness of learning and use of methods and technologies of conducting scientific research, implementation of their results, the continuity of research work according to training courses, the logic of the complication of methods, types and forms of scientific creativity

Development and validation of a method for the quantitative determination of metoprolol succinate in the air of the working area by high-performance liquid chromatography using mass spectra

Introduction. Metoprolol is a cardioselective blocker of β-adrenergic receptors. Drugs containing metoprolol have hypotensive, antianginal, antiarrhythmic effects. Moderately dangerous when taken orally, has a general toxic effect. Metoprolol is produced in two forms: in the form of salts of tartaric and succinic acids, the approximate safe level of exposure to which is 0.3 mg/m3. To ensure the safety of workers, it is necessary to carry out sanitary and hygienic air control. Methods for the quantitative analysis of metoprolol in the air of the working area, presented in the current scientific literature, allow monitoring only for metoprolol salts in the form of tartrate. 
 The aim of the study is to develop and validate an analytical method for the quantitative determination 
 of metoprolol succinate in the air of the working area by HPLC-MS. 
 Materials and methods. For the analysis, standard samples of metoprolol succinate and air samples taken at all stages of the life cycle of the production of the drug metoproolol were used. Chromatographic separation and detection were performed on an Agilent 1260 Infinity G6125B high performance liquid chromatograph (Agilent Technologies, USA) equipped with a column and sample thermostat, a degasser, a pump, an autosampler, and a G6125B mass selective detector. A Waters Xbridge® C18 3.5 µm column was used; 2.1×30 mm (Waters, Ireland). Primary data were processed using Open Lab CDS ChemStation Edition (Rev. C.01.07 SR3) software (Agilent Technologies, USA).
 Results. A method for the quantitative determination of metoprolol succinate in air samples by HPLC-MS has been developed and validated. During the validation of the developed methodology, it was found that the validation characteristics (specificity, linearity, accuracy and precision, correctness, reproducibility) are within the acceptance criteria. The analytical range of the technique was 0.1–10.0 µg/ml and allows the developed technique to be used to control the average shift MPCs in the air of the working area.
 Limitations. The results of the study of the air in the working area are applicable only to the production of the drug metoprolol in the form of tablets; the study of air during the synthesis and packaging of the active pharmaceutical substance was not carried out. 
 Conclusion. An analysis of air samples from the production of the drug metoprolol was carried out and the safety of working conditions was proved.

Microglial reactivity in brainstem chemosensory nuclei in response to hypercapnia.

Microglia, the resident immune cells of the CNS, surveil, detect, and respond to various extracellular signals. Depending on the nature of these signals, an integrative microglial response can be triggered, resulting in a phenotypic transformation. Here, we evaluate whether hypercapnia modifies microglia phenotype in brainstem respiratory-related nuclei. Adult C57BL/6 inbred mice were exposed to 10% CO2 enriched air (hypercapnia), or pure air (control), for 10 or 30min and immediately processed for immunohistochemistry to detect the ubiquitous microglia marker, ionized calcium binding adaptor molecule 1 (Iba1). Hypercapnia for thirty, but not 10min reduced the Iba1 labeling percent coverage in the ventral respiratory column (VRC), raphe nucleus (RN), and nucleus tractus solitarius (NTS) and the number of primary branches in VRC. The morphological changes persisted, at least, for 60min breathing air after the hypercapnic challenge. No significant changes were observed in Iba1+ cells in the spinal trigeminal nucleus (Sp5) and the hippocampus. In CF-1 outbred mice, 10% CO2 followed by 60min of breathing air, resulted in the reduction of Iba1 labeling percent coverage and the number and length of primary branches in VRC, RN, and NTS. No morphological change was observed in Iba1+ cells in Sp5 and hippocampus. Double immunofluorescence revealed that prolonged hypercapnia increased the expression of CD86, an inflammatory marker for reactive state microglia, in Iba1+ cells in VRC, RN, and NTS, but not in Sp5 and hippocampus in CF-1 mice. By contrast, the expression of CD206, a marker of regulatory state microglia, persisted unmodified. In brainstem, but not in hippocampal microglia cultures, hypercapnia increased the level of IL1β, but not that of TGFβ measured by ELISA. Our results show that microglia from respiratory-related chemosensory nuclei, are reactive to prolonged hypercapnia acquiring an inflammatory-like phenotype.

Surface Degradation of Ion-releasing Restorative Materials With Cariogenic Challenge.

This study examined the influence of cariogenic environments on the surface roughness of ion-releasing restorative materials (IRMs). Custom-made stainless steel molds with holes of 5 mm × 2mm were used to fabricate 60 disc-shaped specimens of each of the following materials: Activa Bioactive (AV), Beautifil Bulk Restorative (BB), Cention N (Bulk-fill) (CN), and Filtek Z350XT (FZ) (Control). Baseline surface roughness (Ra) measurements were obtained using an optical 3D measurement machine (Alicona Imaging GmbH, Graz, Austria). The specimens were then randomly divided into five subgroups (n=12) and exposed to 10 ml of the following mediums at 37°C: distilled water (DW), demineralization solution (DM), remineralization solution (RM), pH cycling (PC) and air (AR) (control). Ra measurements were again recorded after one week and one month, followed by statistical evaluations with two-way analysis of variance (ANOVA) to determine interactions between materials and mediums. One-way ANOVA and post hoc Games Howell tests were performed for intergroup comparisons at a significance level of 0.05. Mean Ra values ranged from 0.085 ± 0.004 (µm) to 0.198 ± 0.001 µm for the various material-medium combinations. All IRMs showed significant differences in Ra values after exposure to the aqueous mediums. The smoothest surfaces were observed in the AR for all materials. When comparing materials, AV presented the roughest surfaces for all mediums. All IRM materials showed increased surface roughness over time in all cariogenic environments but were below the threshold value for bacterial adhesion, except for AV 1-month post immersion with pH cycling. Therefore, besides AV, the surface roughness of IRMs did not deteriorate to an extent that it is clinically relevant.

Swarm Division-Based Aircraft Velocity Obstacle Optimization Considering Low-Carbon Emissions

In the pursuit of sustainable aviation, this paper presents an innovative approach that adopts a swarm division strategy to enhance and refine the velocity obstacle (VO) method, guided by a low-carbon principle. A dynamic elliptical protection zone model forms the core of this innovative approach. Specifically, this dynamic elliptical protection zone is created based on the difference in aircraft velocity, and a swarm division strategy is introduced in this process. Initially, aircraft that share the same route and type, and have similar velocities and distances, are grouped into swarms. Then, the characteristics of the swarms, such as mass points, velocities, and protection zones, are recorded. Second, the collision cone (CC) between swarms is established, and planar geometrical analysis is used to determine the optimal relief velocity and heading of aircraft on the low-carbon objective while ensuring a safe interval between aircraft in the swarm during the relief period. Additionally, a swarm control algorithm is utilized to adjust the velocity of the aircraft by a small margin. Finally, simulation experiments are conducted using Python, revealing that the swarm relief efficiency of the enhanced VO method sees a notable increase of over 33%. Concurrently, the need for adjustments decreases by an average of 32.78%, while fuel savings reach as high as 70.18%. The strategy is real-time and operational, significantly reduces the air traffic controller (ATC) workload, improves flight efficiency and safety, and contributes positively to the reduction in carbon emissions, which is beneficial for the environment.

How to measure and control indoor air quality based on intelligent digital twin platforms: A case study in China

In order to address the current disparity between indoor air quality assessment, prediction, and control, this study proposes an intelligent management approach for indoor air quality based on digital twin platforms. By collecting and fusing multi-level, and multi-dimensional data at the physical level, a comprehensive data integration and analysis platform is established in the digital realm, encompassing the ‘Sense-Integrate-Retrieve-Analyze-Feedback’ framework. Various digital technologies, such as the Internet of Things (IoT), Building Information Modeling (BIM), and machine learning, are utilized to integrate and visualize multi-source heterogeneous data through a lightweight web-based interface so that data retrieval, rapid prediction, and intelligent control are feasible based on various backend algorithm models. Compared to traditional measurement methods, this system offers broader spatiotemporal coverage, increased mobility, and less disruption to physical infrastructure, which underscores the sophistication of monitoring technology, data integration, and environmental management. The proposed intelligent platform has been validated in a traditional Chinese dwelling, and practical results demonstrate that most air quality problems occur in the early morning of winter while this system can swiftly predict and issue control signals for adjustments in occupied spaces exceeding predefined healthy thresholds. Field measurements confirmed that most air quality problems can be solved within 30 min after their appearance. By eliminating data silos through real-time synchronization and remote intelligent control via the digital platform, it bridges the gap between problem identification by managers and problem resolution by end-users, ensuring timely responses to indoor air quality concerns.

Attenuated incubation of ethanol-induced conditioned taste aversion in a model of dependence.

Preclinical studies report attenuated ethanol-induced conditioned taste aversion (CTA) following chronic ethanol exposure, suggesting that tolerance develops to the aversive properties of ethanol. However, these studies are confounded by pre-exposure to the unconditioned stimulus (US; ethanol), which is well known to hinder conditioning. This study was designed to determine whether chronic ethanol exposure produces tolerance to the aversive properties of ethanol in the absence of a US pre-exposure confound. CTA was performed in adult male and female Long-Evans rats by pairing 0.1% ingested saccharin with an intraperitoneal injection of ethanol (1.5 or 2.0g/kg) or saline. Rats were then rendered ethanol dependent using chronic intermittent ethanol (CIE) vapor exposure. Controls were exposed to room air (AIR). The effect of chronic ethanol on CTA expression and reconditioning were examined following vapor exposure. Prior to vapor exposure, both sexes developed CTA to a comparable degree with 2.0g/kg producing greater CTA than 1.5g/kg ethanol. Following vapor exposure, AIR controls exhibited an increase in CTA magnitude compared to pre-vapor levels. This effect was largely absent in CIE-exposed rats. Re-conditioning after vapor exposure facilitated increased CTA magnitude to a similar degree in AIR- and CIE-exposed males. In contrast, CTA magnitude was unchanged by re-conditioning in females. These data suggest that chronic ethanol does not facilitate tolerance to the aversive properties of ethanol but rather attenuates incubation of ethanol-induced CTA. Loss of CTA incubation suggests that CIE exposure disrupts circuits encoding aversion.

Adaptable automation for a more human-centered work design? Effects on human perception and behavior

This experiment systematically examines whether, in safety-critical environments such as Air Traffic Control, the negative effects of increasing automation associated with static automation concepts can be mitigated by adaptable automation. Adaptable automation is a form of flexible automation in which the human operator (rather than the system as in adaptive automation) can decide when and to what extent to delegate tasks. A special focus is on its effects on human perception in terms of perceived autonomy and competence, satisfaction, and human role perception. We conducted two online studies using the same dual-task paradigm. Study 1 was conducted with a novice sample via Prolific (N = 93) and study 2 with an expert sample of Air Traffic Controllers (N = 126). Participants were either supported by static information automation, static decision automation, or an adaptable solution that allowed them to switch between the two automation stages. The findings of both studies are similar. Results indicated that, even when humans rarely switched, adaptable automation could increase perceived autonomy, led to high satisfaction, and had positive effects on role perceptions without impairing performance or workload. Furthermore, satisfaction was found to correlate with performance. From a human-centered perspective, flexible concepts seem to be particularly suitable when automation increasingly takes over parts of a job task not only at the stage of information analysis but also at the stage of decision-making.

Development of novel compact wind tunnel for testing efficacy of insecticide formulated products in mosquitoes.

Ultra-low volume (ULV) space sprays aerosolize insecticide formulated products (FP) to contact flying mosquitoes, while barrier sprays expose mosquitoes to FP residue on vegetation and other surfaces. Centers for Disease Control and Prevention bottle bioassays used to assess insecticide resistance are based on residual active ingredient (AI) exposure and do not directly relate to FP efficacy. The current pilot study developed a novel compact wind tunnel for mosquito exposure to FP. Caged Aedes albopictus and Culex pipiens/quinquefasciatus were exposed to undiluted Biomist®3 + 15 FP (permethrin AI) or air (control) within the wind tunnel, transferred to new cages, and held in a 28 °C incubator. Separate mosquitoes were exposed to residual permethrin AI (8 μg mL-1) in bottle bioassays. Mortality was monitored 15, 30, 60, and 120 min post-exposure. Chi-square tests (P < 0.05) showed significantly higher mortality in Aedes compared to Culex populations for most time points in both bioassay and wind tunnel exposure groups. As expected, mosquitoes exposed to Biomist®3 + 15 showed higher mortality rates than bottle bioassay exposure to permethrin. Two Culex colonies resistant to permethrin in bottle bioassays were susceptible to Biomist®3 + 15 in the wind tunnel. The novel compact wind tunnel developed here may be an alternative to field trials for testing FP efficacy, avoiding factors such as weather, logistical planning, and extended personnel hours. The wind tunnel could allow programs to conveniently test efficacy of multiple FP. Comparisons of different insecticide exposure methods provide practical information to inform operational decisions. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Mitigating the Negative Effect of Air Traffic Controller Mental Workload on Job Performance: The Role of Mindfulness and Social Work Support

Air traffic controllers (ATCOs) play a substantial part in securing the safety of flights, such that a compromise of the ATCOs’ performance may lead to tragedies. Given the mental workload that comes with the nature of ATCOs’ work, this study intends to investigate the impact of mental workload on ATCOs’ job performance and identify conditional factors that could mitigate the mental workload–ATCOs’ job performance relationship. Underpinned by the job demands–resources theory, a framework was developed to investigate the impact of job demands (mental workload) on job performance and whether personal resources (mindfulness and social work support) weaken the relationship. A total of 324 ATCOs across Saudi Arabia responded to the questionnaire. There were three notable findings. First, mental workload was indeed found to bring detrimental effects to ATCOs’ job performance. Second, mindfulness played a mitigating role, where more mindful ATCOs demonstrated less workload effect on performance. Thirdly, social work support also played a mitigating role, where ATCOs who perceived receiving greater job support experienced less detrimental impact from the workload on performance. This study verified the negative linkages between mental workload and job performance and identified the boundary conditions (mindfulness and social work support) that weaken the relationship. The limitations and future research directions are then discussed.

The relationship between mindfulness and work-life balance: The mediation role of emotional regulation

Air Traffic Controller (ATC) is one of the occupations in the service sector. ATC, like other jobs, has other social tasks outside of work that require the ability to balance work and family or personal and social responsibilities (i.e., work-life balance). This research aims to test the role of emotional regulation in mediating the relationship between mindfulness and work-life balance among ATC officers. This research was conducted quantitatively. The data was collected through the work-life balance, emotion regulation, and mindfulness scales and was analyzed using structural equation modeling (SEM) operated through the JASP program version 16. 172 employees (59% males) involved in this research. Results showed that emotional regulation significantly mediates the relationship between mindfulness and work-life balance. This indicates that ATC officers with a mindful condition will consciously be able to direct their attention to focus on the current situation and role. This will affect ATC's ability to manage cognitively to provide emotional responses and express emotions according to the needs of the current situation in completing the role at hand and achieving work-life balance. This finding has implications on how management might assist ATC officers in improving work-life balance by enhancing emotional regulation skills and mindfulness.

Air traffic inefficiencies and predictability evaluation using route mapping—the Tokyo International Airport case

Air traffic inefficiencies lead to excess fuel burn, emissions and air traffic controller (ATCo) workload. Various stakeholders have developed metrics to assess the operation performance. Most metrics compare the actual trajectories to some benchmark ones to calculate excess time or distance. This research is inspired by cellular automata (CA) and develops a combined time-distance lateral inefficiency and predictability metric using discrete space and time mapping on published flight routes. The analysis is focused on Tokyo International Airport, but uses only track data and published routes, which makes it easily applicable to any other hub airport worldwide. The mapping and velocity analyses are used to investigate when and where ATCos are most likely to intervene to provide save separation. A metric which can be adjusted to evaluate both traffic flow predictability and efficiency is proposed. This metric can be applied to better understand current traffic and enable future improvements towards seamless air traffic flow management.

Comparative Evaluation of Post-Monsoon Crossroads Air Quality Variations in Major Cities of the Greater Dhaka Region

This study investigates the escalating issue of urban air pollution in Dhaka and its surrounding areas, focusing on the post-monsoon period. Utilizing Aeroqual Series 500 air quality monitors, this research measured concentrations of NO2, SO2, CO2, CH4, PM2.5, and PM10 at 24 strategically selected sites in Dhaka, Narayanganj, and Gazipur. The findings reveal elevated levels of NO2 across multiple regions, notably exceeding the standard threshold of 0.053 ppm, with Gulistan, Mirpur10, Gabtuli Darus-salam, Farmgate, and Savar exhibiting the highest concentrations. Additionally, Gulistan displayed a significant peak in SO2 levels at 0.3 ppm. Areas adjacent to the Buriganga River, specifically Lalbagh and Kadamtuli, were identified as heavily polluted as they have been characterized by strong odour and poor air quality. High concentrations of CH4 and CO2 were detected in the New Market, Zinda Park, and Jirani Bazar, surpassing established safe levels. The study highlights Dhaka's alarming average Air Quality Index (AQI) of 186.8, with a peak of 395 at Joydebpur Rail Station and a low of 110 at Panam City. This research underscores the critical need for enhanced air quality monitoring and control strategies in Dhaka, highlighting the severe health risks posed by industrial and vehicular emissions in rapidly urbanizing regions.

Use of SPO in the work of air traffic controllers in Poland from a work safety perspective

Use of SPO in the work of air traffic controllers in Poland from a work safety perspective

Exposure to Airborne PM2.5 Water-Soluble Inorganic Ions Induces a Wide Array of Reproductive Toxicity.

Water-soluble inorganic ions (WSIIs, primarily NH4+, SO42-, and NO3-) are major components in ambient PM2.5, but their reproductive toxicity remains largely unknown. An animal study was conducted where parental mice were exposed to PM2.5 WSIIs or clean air during preconception and the gestational period. After delivery, all maternal and offspring mice lived in a clean air environment. We assessed reproductive organs, gestation outcome, birth weight, and growth trajectory of the offspring mice. In parallel, we collected birth weight and placenta transcriptome data from 150 mother-infant pairs from the Rhode Island Child Health Study. We found that PM2.5 WSIIs induced a broad range of adverse reproductive outcomes in mice. PM2.5 NH4+, SO42-, and NO3- exposure reduced ovary weight by 24.22% (p = 0.005), 14.45% (p = 0.048), and 16.64% (p = 0.022) relative to the clean air controls. PM2.5 SO42- exposure reduced the weight of testicle by 5.24% (p = 0.025); further, mice in the PM2.5 SO42- exposure group had 1.81 (p = 0.027) fewer offspring than the control group. PM2.5 NH4+, SO42-, and NO3- exposure all led to lower birth than controls. In mice, 557 placenta genes were perturbed by exposure. Integrative analysis of mouse and human data suggested hypoxia response in placenta as an etiological mechanism underlying PM2.5 WSII exposure's reproductive toxicity.

Air Traffic Controller Fatigue Detection by Applying a Dual-Stream Convolutional Neural Network to the Fusion of Radiotelephony and Facial Data

The role of air traffic controllers is to direct and manage highly dynamic flights. Their work requires both efficiency and accuracy. Previous studies have shown that fatigue in air traffic controllers can impair their work ability and even threaten flight safety, which makes it necessary to carry out research into how to optimally detect fatigue in controllers. Compared with single-modality fatigue detection methods, multi-modal detection methods can fully utilize the complementarity between diverse types of information. Considering the negative impacts of contact-based fatigue detection methods on the work performed by air traffic controllers, this paper proposes a novel AF dual-stream convolutional neural network (CNN) architecture that simultaneously extracts controller radio telephony fatigue features and facial fatigue features and performs two-class feature-fusion discrimination. This study designed two independent convolutional processes for facial images and radio telephony data and performed feature-level fusion of the extracted radio telephony and facial image features in the fully connected layer, with the fused features transmitted to the classifier for fatigue state discrimination. The experimental results show that the detection accuracy of radio telephony features under a single modality was 62.88%, the detection accuracy of facial images was 96.0%, and the detection accuracy of the proposed AF dual-stream CNN network architecture reached 98.03% and also converged faster. In summary, a dual-stream network architecture based on facial data and radio telephony data is proposed for fatigue detection that is faster and more accurate than the other methods assessed in this study.

Chronic aryl hydrocarbon receptor activity impairs muscle mitochondrial function with tobacco smoking.

Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated. AHR related gene (mRNA) expression was quantified in skeletal muscle from adult controls and patients with chronic obstructive pulmonary disease (COPD), as well as mice with and without cigarette smoke exposure. Utilizing both skeletal muscle-specific AHR knockout mice exposed to chronic repeated (5days per week for 16weeks) cigarette smoke and skeletal muscle-specific expression of a constitutively active mutant AHR in healthy mice, a battery of assessments interrogating muscle size, contractile function, mitochondrial energetics, and RNA sequencing were employed. Skeletal muscle from COPD patients (N=79, age=67.0±8.4years) had higher levels of AHR (P=0.0451) and CYP1B1 (P<0.0001) compared to healthy adult controls (N=16, age=66.5±6.5years). Mice exposed to cigarette smoke displayed higher expression of Ahr (P=0.008), Cyp1b1 (P<0.0001), and Cyp1a1 (P<0.0001) in skeletal muscle compared to air controls. Cigarette smoke exposure was found to impair skeletal muscle mitochondrial oxidative phosphorylation by ~50% in littermate controls (Treatment effect, P<0.001), which was attenuated by deletion of the AHR in muscle in male (P=0.001), but not female, mice (P=0.37), indicating there are sex-dependent pathological effects of smoking-induced AHR activation in skeletal muscle. Viral mediated expression of a constitutively active mutant AHR in the muscle of healthy mice recapitulated the effects of cigarette smoking by decreasing muscle mitochondrial oxidative phosphorylation by ~40% (P=0.003). These findings provide evidence linking chronic AHR activation secondary to cigarette smoke exposure to skeletal muscle bioenergetic deficits in male, but not female, mice. AHR activation is a likely contributor to the decline in muscle oxidative capacity observed in smokers and AHR antagonism may provide a therapeutic avenue aimed to improve muscle function in COPD.

Impact of prolonged exposure to occasional and regular waterpipe smoke on cardiac injury, oxidative stress and mitochondrial dysfunction in male mice.

Regular waterpipe smoking (Reg-WPS) is well recognized for its deleterious effect on the heart. However, there is a paucity of experimental studies on the impact of occasional waterpipe smoking (Occ-WPS), also known as nondaily smoking, versus Reg-WPS on cardiac homeostasis, and the mechanisms underlying these effects. Hence, we aimed, in the present study, to investigate the effect of Occ-WPS (30min/day, 1day/week) versus Reg-WPS (30min/day, 5days/week) for 6months on systolic blood pressure (SBP), cardiac injury, oxidative markers, chemokines, proinflammatory cytokines, DNA damage and mitochondrial function compared with air (control) exposed mice. Our results show that SBP was increased following exposure to either Occ-WPS or Reg-WPS compared with air-exposed mice. Moreover, we found that only Reg-WPS induced a significant elevation in the levels of troponin I, brain natriuretic peptide, lactate dehydrogenase, and creatine phosphokinase. However, the atrial natriuretic peptide (ANP) was significantly increased in both Occ-WPS and Reg-WPS groups. Compared with air-exposed mice, the levels of lipid peroxidation, reduced glutathione and monocyte chemoattractant protein-1 were only significantly augmented in the Reg-WPS. However, catalase, superoxide dismutase, and CXCL1 were significantly increased in both Occ-WPS and Reg-WPS. The concentrations of the adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 were solely elevated in the heart of mice exposed to Reg-WPS. Similarly, the concentrations of interleukin-1β and tumor necrosis factor α were only significantly augmented in the Reg-WPS. However, both Occ-WPS and Reg-WPS triggered significant augmentation in the levels of IL17 and DNA damage compared to the control groups. Furthermore, while Occ-WPS induced a slight but statistically insignificant elevation in the concentrations of mammalian targets of rapamycin and nuclear factor erythroid-derived 2-like 2 (Nrf2) expression, Reg-WPS exposure increased their levels substantially, in addition to p53 and mitochondrial complexes II & III, and IV activities compared with air-exposed mice. In conclusion, our findings show that while the long-term Occ-WPS exposure induced an elevation of SBP, ANP, antioxidant enzymes, IL17, CXCL1, and cardiac DNA damage, Reg-WPS exposure was consistently associated with the elevation of SBP and occurrence of cardiac damage, inflammation, oxidative stress, DNA damage and mitochondrial dysfunction.