MiXie, an Online Tool for Better Health Assessment of Workers Exposed to Multiple Chemicals

There is increasing concern for workers facing multiple chemical exposure. The accumulation of information on occupational conditions indicates the need to incorporate the concept of multiple exposures in the risk assessment process and to develop tools for assessing the potential impacts of multiple exposures on workers’ health. Our objective is to describe the MiXie online decision-making tool that can be used to assess the risk of exposure to multiple chemicals. The description includes the development of MiXie, the structure of its toxicological database according to the target organ or the mode of action, and the algorithm for quantitative analysis of a mixture. Two case studies of its use in evaluating the risks of multiple exposures in real workplace situations are presented. The case study in the printing industry showed increased risk for four toxicological classes (central nervous system damage, ocular damage, skin damage, and ototoxicity) associated with co-exposure to four chemicals during maintenance operations. The MiXie analysis also showed the presence of carcinogenic substances in the mixture and a risk to the development of the foetus. The case study in nail salons showed the presence of carcinogenic and sensitizing chemicals and an increased risk to upper airways. MiXie helps preventers evaluate the possible additive effects of mixtures, providing an easy-to-read diagnosis to identify risks incurred by co-exposed employees. In addition, MiXie identifies risky occupational situations that would go unnoticed without a multiple substance approach.

Molecular Characterization of Fungal Colonization on the Provox™ Tracheoesophageal Voice Prosthesis in Post Laryngec-tomy Patients

Background: Tracheoesophageal voice prostheses (TVPs) have been the gold standard in rehabilitation, after laryngectomy, producing faster and premier voicing towards esophageal speech. Fungal colonization shortens the device’s lifetime and leads to prosthesis dysfunction, leakage, and subsequent respiratory infection. Therefore, in the current study, we aimed to investigate the fungal colonization patterns and to propose prophylactic measures that shall increase the longevity of voice prosthesis. Methods: Failed TVPs were removed - due to leakage and/or aspiration - from 66 post laryngectomy patients and examined. They were referred to Amiralam and Rasoul Hospital, the main centers of Ear, Nose, and Throat in Tehran, Iran from April 2018 to January 2020. Fungal colonization patterns were assessed using DNA sequencing techniques. Furthermore, the susceptibility to fluconazole, amphotericin B, nystatin, and white vinegar was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Resident fungal species from the upper airways colonized all the 66 TVPs (100%). Diabetes (31%) and smoking (98%) were the predominant underlying disease and predisposing factors, respectively. Among the 79 fungal agents isolated from the 66 TVPs, Candida glabrata (n=25, 31.7%) was the most common. A significant reduction in minimum inhibitory concentration (MIC) values were observed for white vinegar when used alone (P<0.05). Conclusion: White vinegar at a very low concentration could decrease the amount of fungal colonization on TVPs without any adverse effects; its wide accessibility and affordability ensure a decrease in the overall health cost.

COVID-19 symptoms reduce with targeted hydration of the nose, larynx and trachea

Dirty air and poor access to healthcare threatens the lives of billions of people in low-income regions of the world. We investigated whether upper-airway hydration might alter two-phase flow in the airways on normal tidal breathing and be a useful, safe, easily distributed non-drug intervention for limiting risks of COVID-19. In observational human volunteer studies involving 464 human subjects in Marburg, Germany (357 normal subjects), Boston, US (20 healthy subjects), and Bangalore, India (87 subjects recently tested positive for COVID-19), we find that respiratory droplet generation increases by up to 4 orders of magnitude with up to 1% total body mass dehydration (n=20), and in dehydration-associated states of advanced age (n=357), elevated BMI-age (n=148), and SARS-CoV-2 infection (n=87). Hydration of the nose, larynx and trachea in a protocol of exercise-induced dehydration by the nasal inhalation of calcium-rich hypertonic salt droplets of mean diameter 8-12 µm diminished respiratory droplet numbers and increased oxygenation relative to a non-treatment control (P<0.05). In a randomized double-blinded nasal-saline control study, thrice-a-day delivery of the calcium-rich hypertonic salts (active) over three days suppressed respiratory droplet generation by 51% +/- 11% and increased oxygen saturation by 48.08% ± 9.61% (P<0.001) in COVID-19 positive subjects (n=20), while no changes in exhaled aerosol (P=0.235) or oxygen saturation (P=0.533) were observed in the nasal-saline control group (n=20). In the active group 47% of patients discharged with no self-reported symptoms while all of the subjects in the nasal saline group discharged with lingering symptoms. Hydration of the upper airways appears promising as a non-drug approach for reducing risks of lower respiratory-tract infections such as COVID-19.

Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients—Possible Mechanisms Involved and Clinical Implication

Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused by the collapse of the upper airways, which results in intermittent hypoxia and arousals during the night. The disorder is associated with a vast number of comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, and neurological complications. Due to abnormal sleep architecture, OSA patients are at high risk of circadian clock disruption, as has been reported in several recent studies. The circadian clock affects almost all daily behavioral patterns, as well as a plethora of physiological processes, and might be one of the key factors contributing to OSA complications. An intricate interaction between the circadian clock and hypoxia may further affect these processes, which has a strong foundation on the molecular level. Recent studies revealed an interaction between hypoxia-inducible factor 1 (HIF-1), a key regulator of oxygen metabolism, and elements of circadian clocks. This relationship has a strong base in the structure of involved elements, as HIF-1 as well as PER, CLOCK, and BMAL, belong to the same Per-Arnt-Sim domain family. Therefore, this review summarizes the available knowledge on the molecular mechanism of circadian clock disruption and its influence on the development and progression of OSA comorbidities.

Ferrets are valuable models for SARS-CoV-2 research

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an ongoing pandemic with millions of deaths worldwide. Infection of humans can be asymptomatic or result in fever, fatigue, dry cough, dyspnea, and acute respiratory distress syndrome with multiorgan failure in severe cases. The pathogenesis of COVID-19 is not fully understood, and various models employing different species are currently applied. Ferrets can be infected with SARS-CoV-2 and efficiently transmit the virus to contact animals. In contrast to hamsters, ferrets usually show mild disease and viral replication restricted to the upper airways. Most reports have used the intranasal inoculation route, while the intratracheal infection model is not well characterized. Herein, we present clinical, virological, and pathological data from young ferrets intratracheally inoculated with SARS-CoV-2. Infected animals showed no significant clinical signs, and had transient infection with peak viral RNA loads at 4 days postinfection, mild to moderate rhinitis, and pulmonary endothelialitis/vasculitis. Viral antigen was exclusively found in the respiratory epithelium of the nasal cavity, indicating a particular tropism for cells in this location. Viral antigen was associated with epithelial damage and influx of inflammatory cells, including activated neutrophils releasing neutrophil extracellular traps. Scanning electron microscopy of the nasal respiratory mucosa revealed loss of cilia, shedding, and rupture of epithelial cells. The currently established ferret SARS-CoV-2 infection models are comparatively discussed with SARS-CoV-2 pathogenesis in mink, and the advantages and disadvantages of both species as research models for zoonotic betacoronaviruses are highlighted.

Modeling of nursing care-associated airborne transmission of SARS-CoV-2 in a real-world hospital setting

Respiratory transmission of SARS-CoV-2 from one older patient to another by airborne mechanisms in hospital and nursing home settings represents an important health challenge during the COVID-19 pandemic. However, the factors that influence the concentration of respiratory droplets and aerosols that potentially contribute to hospital- and nursing care-associated transmission of SARS-CoV-2 are not well understood. To assess the effect of health care professional (HCP) and patient activity on size and concentration of airborne particles, an optical particle counter was placed (for 24 h) in the head position of an empty bed in the hospital room of a patient admitted from the nursing home with confirmed COVID-19. The type and duration of the activity, as well as the number of HCPs providing patient care, were recorded. Concentration changes associated with specific activities were determined, and airway deposition modeling was performed using these data. Thirty-one activities were recorded, and six representative ones were selected for deposition modeling, including patient’s activities (coughing, movements, etc.), diagnostic and therapeutic interventions (e.g., diagnostic tests and drug administration), as well as nursing patient care (e.g., bedding and hygiene). The increase in particle concentration of all sizes was sensitive to the type of activity. Increases in supermicron particle concentration were associated with the number of HCPs (r = 0.66; p < 0.05) and the duration of activity (r = 0.82; p < 0.05), while submicron particles increased with all activities, mainly during the daytime. Based on simulations, the number of particles deposited in unit time was the highest in the acinar region, while deposition density rate (number/cm2/min) was the highest in the upper airways. In conclusion, even short periods of HCP-patient interaction and minimal patient activity in a hospital room or nursing home bedroom may significantly increase the concentration of submicron particles mainly depositing in the acinar regions, while mainly nursing activities increase the concentration of supermicron particles depositing in larger airways of the adjacent bed patient. Our data emphasize the need for effective interventions to limit hospital- and nursing care-associated transmission of SARS-CoV-2 and other respiratory pathogens (including viral pathogens, such as rhinoviruses, respiratory syncytial virus, influenza virus, parainfluenza virus and adenoviruses, and bacterial and fungal pathogens).

A machine-learning-based method for automatizing lattice-Boltzmann simulations of respiratory flows

Many simulation workflows require to prepare the data for the simulation manually. This is time consuming and leads to a massive bottleneck when a large number of numerical simulations is requested. This bottleneck can be overcome by an automated data processing pipeline. Such a novel pipeline is developed for a medical use case from rhinology, where computer tomography recordings are used as input and flow simulation data define the results. Convolutional neural networks are applied to segment the upper airways and to detect and prepare the in- and outflow regions for accurate boundary condition prescription in the simulation. The automated process is tested on three cases which have not been used to train the networks. The accuracy of the pipeline is evaluated by comparing the network-generated output surfaces to those obtained from a semi-automated procedure performed by a medical professional. Except for minor deviations at interfaces between ethmoidal sinuses, the network-generated surface is sufficiently accurate. To further analyze the accuracy of the automated pipeline, flow simulations are conducted with a thermal lattice-Boltzmann method for both cases on a high-performace computing system. The comparison of the results of the respiratory flow simulations yield averaged errors of less than 1% for the pressure loss between the in- and outlets, and for the outlet temperature. Thus, the pipeline is shown to work accurately and the geometrical deviations at the ethmoidal sinuses to be negligible.

Nonlinear signal processing, spectral, and fractal based stridor auscultation: A machine learning approach

The work reported in the paper analyses the adventitious stridor breath sound (ST) and the normal bronchial breath sound (BR) using spectral, fractal, and nonlinear signal processing methods. The sixty breath sound signals are subjected to power spectral density (PSD) and wavelet analyses to understand the temporal evolution of the frequency components. The energy envelope of the PSD plot of ST shows three peaks labelled as A (256 Hz), B (369 Hz), and C (540 Hz), of which A alone is present in BR at 265 Hz. The appearance of B and C in the PSD plot of ST is due to the obstructions in the trachea and upper airways caused by lesions. The phase portrait analysis of the time series data of ST and BR gives information about the randomness and the sample entropy of the dynamical system. The study reveals that the fractal dimension and sample entropy values are higher for BR, which may be due to the musical ordered behaviour of ST. The machine learning techniques based on the features extracted from the PSD data and phase portrait parameters offer good predictability, besides the classification of BR and ST, and thereby revealing its potential in pulmonary auscultation.

Osteopathic Manipulation of the Sphenopalatine Ganglia Versus Sham Manipulation, in Obstructive Sleep Apnoea Syndrom: A Randomised Controlled Trial

(1) Background: osteopathic manipulation of the sphenopalatine ganglia (SPG) blocks the action of postganglionic sensory fibres. This neuromodulation can reduce nasal obstruction and enhance upper airway stability. We investigated the manipulation of the SPG in 31 patients with obstructive sleep apnoea syndrome (OSAS); (2) Methods: Randomised, controlled, double-blind, crossover study. Participants received active (AM), then sham manipulation (SM), or vice versa. The primary endpoint was apnoea-hypopnoea index (AHI). Secondary endpoints were variation of nasal obstruction evaluated by peak nasal inspiratory flow (PNIF) and upper airways stability evaluated by awake critical closing pressure [awake Pcrit]), at 30 min and 24 h. Schirmer’s test and pain were assessed immediately post-manipulation. Tactile/gustatory/olfactory/auditory/nociceptive/visual sensations were recorded. Adverse events were collected throughout. (3) Results: SPG manipulation did not reduce AHI (p = 0.670). PNIF increased post-AM but not post-SM at 30 min (AM-SM: 18 [10; 38] L/min, p = 0.0001) and 24 h (23 [10; 30] L/min, p = 0.001). There was no significant difference on awake Pcrit (AM-SM) at 30 min or 24 h). Sensations were more commonly reported post-AM (100% of patients) than post-SM (37%). Few adverse events and no serious adverse events were reported. (4) Conclusions: SPG manipulation is not supported as a treatment for OSAS but reduced nasal obstruction. This effect remains to be confirmed in a larger sample before using this approach to reduce nasal congestion in CPAP-treated patients or in mild OSAS.