In silico identification of viral loads in cough-generated droplets - Seamless integrated analysis of CFPD-HCD-EWF.

BACKGROUND AND OBJECTIVE: Respiratory diseases caused by respiratory viruses have significantly threatened public health worldwide. This study presents a comprehensive approach to predict viral dynamics and the generation of stripped droplets within the mucus layer of the respiratory tract during coughing using a larynx-trachea-bifurcation (LTB) model. METHODS: This study integrates computational fluid-particle dynamics (CFPD), host-cell dynamics (HCD), and the Eulerian wall film (EWF) model to propose a potential means for seamless integrated analysis. The verified CFPD-HCD coupling model based on a 3D-shell model was used to characterize the severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) dynamics in the LTB mucus layer, whereas the EWF model was employed to account for the interfacial fluid to explore the generation mechanism and trace the origin site of droplets exhaled during a coughing event of an infected host. RESULTS: The results obtained using CFPD delineated the preferential deposition sites for droplets in the laryngeal and tracheal regions. Thus, the analysis of the HCD model showed that the viral load increased rapidly in the laryngeal region during the peak of infection, whereas there was a growth delay in the tracheal region (up to day 8 after infection). After two weeks of infection, the high viral load gradually migrated towards the glottic region. Interestingly, the EWF model demonstrated a high concentration of exhaled droplets originating from the larynx. The coupling technique indicated a concurrent high viral load in the mucus layer and site of origin of the exhaled droplets. CONCLUSIONS: This interdisciplinary research underscores the seamless analysis from initial exposure to virus-laden droplets, the dynamics of viral infection in the LTB mucus layer, and the re-emission from the coughing activities of an infected host. Our efforts aimed to address the complex challenges at the intersection of viral dynamics and respiratory health, which can contribute to a more detailed understanding and targeted prevention of respiratory diseases.

Job Satisfaction within the Grassroots Healthcare System in Vietnam's Key Industrial Region-Binh Duong Province: Validating the Vietnamese Version of the Minnesota Satisfaction Questionnaire Scale.

Background: The grassroots healthcare system is the closest and most community-oriented force, working as an extended arm of the primary healthcare network to implement healthcare programs at the household level. Its comprehensive development is a crucial task set by the Vietnamese government. Job satisfaction significantly influences the performance of healthcare staff within this system. Objective: to assess job satisfaction among healthcare staff using the short-form of the Minnesota Satisfaction Questionnaire while also evaluating the Vietnamese translation of this scale. Methods: A descriptive cross-sectional study with analysis based on the responses of 587 healthcare staff using the Vietnamese-translated version of the MSQ short-form scale. The response data from the participants were subjected to CFA, and if the proposed CFA model did not fit the data, EFA was conducted. Results: The results indicate that the new model, which evaluates job-related factors in three distinct groups, is more suitable than the original model. The 14 questions of the MSQ scale were analyzed and categorized into Autonomy, Obligation, and Specificity based on the participants' responses. The confirmatory factor analysis (CFA) conducted on the new model demonstrated favorable fit indices: CFI = 0.934, TLI = 0.917, GFI = 0.919, and RMSEA = 0.093 (90% CI: 0.085-0.102). Conclusions: The Vietnamese version of the MSQ short form demonstrates reliability and validity. It also provides additional data on the effectiveness of the MSQ short form in measuring job satisfaction.

Prevalence and Factors Affecting Appropriate Inhaler Use in Elderly Patients with Chronic Obstructive Pulmonary Disease: A Prospective Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) mainly affects individuals aged 60 and older. The proper use of inhalers is crucial for managing COPD. This study aimed to evaluate the prevalence and factors affecting the appropriate use of inhalers among elderly patients with COPD. METHODS: We enrolled 91 elderly patients with COPD admitted to the Department of Respiratory, University Medical Center HCMC between October 2020 and May 2021. Patients who were capable of using the inhaler would have their inhaler usage recorded through video footage. Two respiratory experts carefully analyzed 133 video-recorded demonstrations for evaluation purposes. RESULTS: 18.7% of the patients demonstrated the correct inhaler technique. Pressurized metered dose inhaler (pMDI) and Turbuhaler had the lowest documented correct usage rates (11.9% and 10.0%, respectively). Two critical steps, namely "holding breath for about five seconds or as long as comfortable" and "breathing out gently," were commonly performed incorrectly when using pMDI, Respimat, Breezhaler, or Turbuhaler. Multivariable logistic regression analysis showed that lower mMRC scores (AOR = 5.3, CI 1.1-25.5, p = 0.037) and receiving inhaler instruction within the past three months (AOR = 5.2, CI 1.3-20.1, p = 0.017) were associated with increased odds of using the inhaler correctly. CONCLUSIONS: Our study found that less than 20% of elderly patients with COPD use inhalers correctly. Common errors include inadequate breath-holding and gentle exhalation. mMRC scores and recent inhaler instruction were predictors of proper use. These findings can aid clinicians in improving inhaler management for elderly patients with COPD.

Computational fluid-particle dynamics modeling of ultrafine to coarse particles deposition in the human respiratory system, down to the terminal bronchiole.

BACKGROUND AND OBJECTIVES: Suspended respirable airborne particles are associated with human health risks and especially particles within the range of ultrafine (< 0.1 µm) or fine (< 2.5 µm) have a high possibility of penetrating the lung region, which is concerned to be closely related to the bronchial or alveoli tissue dosimetry. Nature complex structure of the respiratory system requires much effort to explore and comprehend the flow and the inhaled particle dynamics for precise health risk assessment. Therefore, this study applied the computational fluid-particle dynamics (CFPD) method to elucidate the deposition characteristics of ultrafine-to-coarse particles in the human respiratory tract from nostrils to the 16th generation of terminal bronchi. METHODS: The realistic bronchi up to the 8th generation are precisely and perfectly generated from computed tomography (CT) images, and an artificial model compensates for the 9th-16th bronchioles. Herein, the steady airflow is simulated at constant breathing flow rates of 7.5, 15, and 30 L/min, reproducing human resting-intense activity. Then, trajectories of the particle size ranging from 0.002 - 10 µm are tracked using a discrete phase model. RESULTS: Here, we report reliable results of airflow patterns and particle deposition efficiency in the human respiratory system validated against experimental data. The individual-related focal point of ultrafine and fine particles deposition rates was actualized at the 8th generation; whilst the hot-spot of the deposited coarse particles was found in the 6th generation. Lobar deposition characterizes the dominance of coarse particles deposited in the right lower lobe, whereas the left upper-lower and right lower lobes simultaneously occupy high deposition rates for ultrafine particles. Finally, the results indicate a higher deposition in the right lung compared to its counterpart. CONCLUSIONS: From the results, the developed realistic human respiratory system down to the terminal bronchiole in this study, in coupling with the CFPD method, delivers the accurate prediction of a wide range of particles in terms of particle dosimetry and visualization of site-specific in the consecutive respiratory system. In addition, the series of CFPD analyses and their results are to offer in-depth information on particle behavior in human bronchioles, which may benefit health risk assessment or drug delivery studies.

Effect of transient breathing cycle on the deposition of micro and nanoparticles on respiratory walls.

BACKGROUND AND OBJECTIVE: From various perspectives (e.g. inhalation exposure and drug delivery), it is important to provide insights into the behavior of inhaled particles in the human respiratory system. Although most of the experimental and numerical studies have relied on an assumption of steady inhalation, the transient breathing profile is a key factor in particle deposition in the respiratory tract. In this study, particle transportation and deposition were predicted in a realistic human airway model during a breathing cycle and the effects of steady-state and transient flows on the deposition fraction were observed using computational fluid dynamics. METHODS: Two transient breathing cycles with different respiratory durations were considered to evaluate the effects of respiration duration on particle transport and deposition characteristics. Two types of steady breathing conditions with corresponding steady-state respiratory volumes were reproduced. The Lagrangian discrete phase model approach was used to investigate particle transportation and deposition under transient breathing conditions. Additionally, the Eulerian approach was used to analyze the transport of nanoparticles in the gas phase. A total of >50,000 monodispersed particles with aerodynamic diameters ranging between 2 nm and 10 µm were selected for comprehensive deposition predictions for particle sizes ranging from the nano- to microscale. RESULTS: The predicted results were compared with the experimental data. The particle deposition fraction in the nasal cavity and tracheal regions showed differences between the steady and transient simulations. In addition, particle analysis under steady inhalation conditions cannot accurately predict particle transportation and deposition in the lower airway. Furthermore, the breathing cycle had a significant effect on the deposition fraction of the particles and the behavior of the inhaled particles. CONCLUSIONS: Transient simulation mimicking the breathing cycle was observed to be an important factor in accurately predicting the transportation and deposition of particles in the respiratory tract.

In-silico decongested trial effects on the impaired breathing function of a bulldog suffering from severe brachycephalic obstructive airway syndrome.

BACKGROUND AND OBJECTIVE: Brachycephalic obstructive airway syndrome (BOAS) susceptible dogs (e.g., French bulldog), suffer health complications related to deficient breathing primarily due to anatomical airway geometry. Surgical interventions are known to provide acceptable functional and cosmetic results; however, the long-term post-surgery outcome is not well known. In silico analysis provides an objective measure to quantify the respiratory function in postoperative dogs which is critical for successful long-term outcomes. A virtual surgery to open the airway can explore the ability for improved breathing in an obstructed airway of a patient dog, thus supporting surgeons in pre-surgery planning using computational fluid dynamics. METHODS: In this study five surgical interventions were generated with a gradual increment of decongested levels in a bulldog based on computed tomography images. The effects of the decongested airways on the breathing function of a patient bulldog, i.e., airflow characteristics, pressure drop, wall shear stress, and air-conditioning capacity, were quantified by benchmarking against a clinically healthy bulldog using computational fluid dynamics (CFD) method. RESULTS: Our findings demonstrated a promising decrease in excessive airstream velocity, pressure drop, and wall shear stress in virtual surgical scenarios, while constantly preserving adequate air-conditioning efficiency. A linear fit curve was proposed to correlate the reduction in the pressure drop and decongested level. CONCLUSIONS: The in silico analysis is a viable tool providing visual and quantitative insight into new unexplored surgical techniques.

Hemodynamic changes associated with common EEG patterns in critically ill patients: Pilot results from continuous EEG-fNIRS study.

Functional near-infrared spectroscopy (fNIRS) is currently the only non-invasive method allowing for continuous long-term assessment of cerebral hemodynamic. We evaluate the feasibility of using continueous electroencephalgraphy (cEEG)-fNIRS to study the cortical hemodynamic associated with status epilepticus (SE), burst suppression (BS) and periodic discharges (PDs). Eleven adult comatose patients admitted to the neuroICU for SE were recruited, and cEEG-fNIRS monitoring was performed to measure concentration changes in oxygenated (HbO) and deoxygenated hemoglobin (HbR). Seizures were associated with a large increase HbO and a decrease in HbR whose durations were positively correlated with the seizures' length. Similar observations were made for hemodynamic changes associated with bursts, showing overall increases in HbO and decreases in HbR relative to the suppression periods. PDs were seen to induce widespread HbO increases and HbR decreases. These results suggest that normal neurovascular coupling is partially retained with the hemodynamic response to the detected EEG patterns in these patients. However, the shape and distribution of the response were highly variable. This work highlighted the feasibility of conducting long-term cEEG-fNIRS to monitor hemodynamic changes over a large cortical area in critically ill patients, opening new routes for better understanding and management of abnormal EEG patterns in neuroICU.

Computational fluid dynamics comparison of impaired breathing function in French bulldogs with nostril stenosis and an examination of the efficacy of rhinoplasty.

BACKGROUND: Brachycephalic obstructive airway syndrome (BOAS) in dogs indicates a particular set of upper airway abnormalities found in brachycephalic dogs (e.g., French bulldogs). Stenotic nares is one of the primary BOAS-related abnormalities restricting the functional breathing of affected dogs. For severe stenosis, rhinoplasty is required to increase the accessibility of the external nostril to air; however, the specific improvement from surgery in terms of respiratory physiology and uptake of inhaled air has not been fully elucidated METHOD: This study employed Computational Fluid Dynamics (CFD) simulations to evaluate the effects of different stenotic intensities on airflow patterns in a total of eight French bulldog upper airways. A bulldog with severe stenosis after surgery was included to examine the efficacy of the surgical intervention. RESULTS: The results showed homogeneous airflow distributions in healthy and mild stenosis cases and significantly accelerated airstreams at the constricted positions in moderate and severe stenosis bulldogs. The airflow resistance was over 20-fold greater in severe stenosis cases than the healthy cases. After surgery, a decrease in airflow velocity was observed in the surgical region, and the percentage of reduced airflow resistance was approximately 4%. CONCLUSIONS: This study suggests impaired breathing function in brachycephalic dogs with moderate and severe stenosis. The results also serve as a reference for veterinarians in surgical planning and monitoring bulldogs' recuperation after surgery.

Inhalation airflow and ventilation efficiency in subject-specific human upper airways.

The present numerical study investigated the transportation time of the inhaled chemicals in three realistic human airway models by adopting a methodology from the field of the building ventilation. Two indexes including "scale of ventilation efficiency 3 (SVE3)" and "local purging flow rate (L-PFR)" were used to evaluate the respective arrival time and staying time under different inhalation flow rates. The general trend of the SVE3 was predicted as expected and the exceptions within the nasal cavities were attributed to the uneven allocation of the inhaled flow between the internal channels and the formation of the vortex circulation therein. The complicated situation of the L-PFR was also explained by the structure constrains. Moreover, the variation of the two indexes with the flow rate was sensitive to the inter-subjective differences but the distribution pattern was not changed significantly. By combining the SVE3 and L-PFR, it could help with assessing the potential effect of the inhaled chemicals on the human health for engineering applications to which the relative impacts are more interested than the absolute value. But for the precise evaluation regarding a specific chemical, comprehensive simulation is still necessary with the surface adsorption included under realistic respiration cycles.

CFD analysis of the flow structure in a monkey upper airway validated by PIV experiments.

Inhalation exposure to airborne contaminants has adverse effects on humans; however, related research is typically conducted using in vivo/in vitro tests on animals. Extrapolating the test results is complicated by anatomical and physiological differences between animals and humans and a lack of understanding of the transport mechanism inside their respective respiratory tracts. This study determined the detailed air-flow structure in the upper airway of a monkey. A steady computational fluid dynamics simulation, which was validated by previous particle image velocimetry measurements, was adopted for flow rates of 4 L/min and 10 L/min to analyze the flow structure from the nasal/oral cavities to the trachea region in a monkey airway model. The low Reynolds number type k-ε model provided a reasonably accurate prediction of the airflow in a monkey upper airway. Furthermore, it was confirmed that large velocity gradients were generated in the nasal vestibule and larynx regions, as well as increased turbulent air kinetic energy and wall sheer stress.

Real-time monitoring of NADPH levels in living mammalian cells using fluorescence-enhancing protein bound to NADPHs.

Nicotinamide adenine nucleotide phosphate (NADPH) has been known to be involved in the multiple pathways of cell metabolism. However, conventional quantification assays for NADPH have required breaking down the cell membranes of around one million cells per assay, and monitoring NADPH flux in living cells has been limited by a few available tools. Here, we visualized NADPH levels in human cervical cancer cells HeLa using metagenome-derived blue fluorescent protein (mBFP), which specifically binds to NADPH and enhances the intrinsic fluorescence of NADPH up to 10-fold when imaged by two-photon microscopy to reduce photodamage. Adding an oxidizing agent such as diamide to HeLa cells that expressed mBFP led to an immediate decrease of intracellular NADPH depending on glucose availability in culture media. Furthermore, inhibiting glucose-6-phosphate dehydrogenase (G6PD) in the pentose phosphate pathway with dehydroandrosterone (DHEA) and knockdown of G6PD transcripts gradually decreased NADPH when diamide was added to living cells. These results demonstrate that introducing a bacterial mBFP gene into mammalian cells is a straightforward approach to monitoring intracellular NADPH flux in real time at the single-cell level. Moreover, this strategy can be expanded to tracking the spatio-temporal changes in NADPH even in single-cell organelles such as mitochondria and chloroplasts, which will allow us to more precisely assess the efficacy of biochemically or biophysically metabolic perturbations in animal and plant cells.

The utility of magnetoencephalography in the presurgical evaluation of refractory insular epilepsy.

PURPOSE: To study the utility of magnetoencephalography (MEG) in patients with refractory insular epilepsy. Covered by highly functional temporal, frontal, and parietal opercula, insular-onset seizures can manifest a variety of ictal symptoms falsely leading to a diagnosis of temporal, frontal, or parietal lobe seizures. Lack of recognition of insular seizures may be responsible for some epilepsy surgery failures. METHODS: We retrospectively reviewed and analyzed MEG data in 14 patients with refractory insular seizures defined through intracranial electroencephalography (EEG) or by the presence of an epileptogenic lesion in the insula with compatible seizure semiology. MEG was performed as part of the noninvasive presurgical evaluation, using a 275-channel whole head MEG system. MEG data were analyzed using a single equivalent current dipole model. MEG localization was compared to interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) results and to the resection margin. KEY FINDINGS: Three patterns of MEG spike sources were observed. Seven patients showed an anterior operculoinsular clusters and two patients had a posterior operculoinsular cluster. No spikes were detected in one patient, and the remaining four patients showed a diffuse perisylvian distribution. Spike sources showed uniform orientation perpendicular to the sylvian fissure. Nine patients proceeded to insular epilepsy surgery with favorable surgical outcome. Among patients with anterior operculoinsular cluster who proceeded to have surgery, MEG provided superior information to ictal SPECT in four of six patients and to interictal PET in five of six patients. SIGNIFICANCE: MEG is useful in identifying patients who are likely to benefit from epilepsy surgery targeting the insula, particularly if a tight dipole cluster is identified even if other noninvasive modalities fail to produce localizing results.

Induced gamma-band response to fragmented images: An intracranial EEG study.

Induced gamma-band response (iGBR) has been linked to coherent perception of images and is thought to represent the synchronisation of neuronal populations mediating binding of elements composing the image and the comparisons with memory for proper recognition. This study uses fragmented images with intracranial electroencephalography to investigate the precise spatio-temporal dynamic of iGBR elicited by the recognition of objects presented for the first time and 24h later. Results show an increased iGBR at recognition in regions involved in bottom-up processes such as the cuneus and the lateral occipital complex. Top-down facilitation involved the lingual gyrus, the precuneus and the superior parietal lobule when images were presented for the first time. Twenty-four hours later, top-down facilitation was mediated by frontal areas involved in retrieval from episodic memory. This study showed that the classically reported iGBR is related to object recognition and that top-down processes vary according to task demand.

SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function.

Several genes predisposing to autism spectrum disorders (ASDs) with or without epilepsy have been identified, many of which are implicated in synaptic function. Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis. This nonsense mutation was found in all affected individuals from a large French-Canadian family segregating epilepsy and ASDs. Additional mutations in SYN1 (A51G, A550T and T567A) were found in 1.0 and 3.5% of French-Canadian individuals with autism and epilepsy, respectively. The majority of these SYN1 mutations were clustered in the proline-rich D-domain which is substrate of multiple protein kinases. When expressed in synapsin I (SynI) knockout (KO) neurons, all the D-domain mutants failed in rescuing the impairment in the size and trafficking of synaptic vesicle pools, whereas the wild-type human SynI fully reverted the KO phenotype. Moreover, the nonsense Q555X mutation had a dramatic impact on phosphorylation by MAPK/Erk and neurite outgrowth, whereas the missense A550T and T567A mutants displayed impaired targeting to nerve terminals. These results demonstrate that SYN1 is a novel predisposing gene to ASDs, in addition to epilepsy, and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.