Respiratory aerosol particle emission and simulated infection risk is greater during indoor endurance than resistance exercise.

Pathogens such as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), influenza, and rhinoviruses are transmitted by airborne aerosol respiratory particles that are exhaled by infectious subjects. We have previously reported that the emission of aerosol particles increases on average 132-fold from rest to maximal endurance exercise. The aims of this study are to first measure aerosol particle emission during an isokinetic resistance exercise at 80% of the maximal voluntary contraction until exhaustion, second to compare aerosol particle emission during a typical spinning class session versus a three-set resistance training session. Finally, we then used this data to calculate the risk of infection during endurance and resistance exercise sessions with different mitigation strategies. During a set of isokinetic resistance exercise, aerosol particle emission increased 10-fold from 5,400 ± 1,200 particles/min at rest to 59,000 ± 69,900 particles/min during a set of resistance exercise. We found that aerosol particle emission per minute is on average 4.9-times lower during a resistance training session than during a spinning class. Using this data, we determined that the simulated infection risk increase during an endurance exercise session was sixfold higher than during a resistance exercise session when assuming one infected participant in the class. Collectively, this data helps to select mitigation measures for indoor resistance and endurance exercise classes at times where the risk of aerosol-transmitted infectious disease with severe outcomes is high.

Lung aerosol particle emission increases with age at rest and during exercise.

Airborne respiratory aerosol particle transmission of pathogens such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), influenza, or rhinoviruses plays a major role in the spread of infectious diseases. The infection risk is increased during indoor exercise, as aerosol particle emission can increase by more than 100-fold from rest to maximal exercise. Earlier studies have investigated the effect of factors such as age, sex, and body mass index (BMI), but only at rest and without taking ventilation into account. Here, we report that during both rest and exercise, subjects aged 60 to 76 y emit on average more than twice as many aerosol particles per minute than subjects aged 20 to 39 y. In terms of volume, older subjects emit on average five times as much dry volume (i.e., the residue of dried aerosol particles) than younger subjects. There was no statistically significant effect of sex or BMI within the test group. Together, this suggests that aging of the lung and respiratory tract is associated with an increased generation of aerosol particles irrespective of ventilation. Our findings demonstrate that age and exercise increase aerosol particle emission. In contrast, sex or BMI only have minor effects.

Aerosol particle emission increases exponentially above moderate exercise intensity resulting in superemission during maximal exercise.

Many airborne pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are transmitted indoors via aerosol particles. During exercise, pulmonary ventilation can increase over 10-fold, and therefore, exercisers will exhale a greater volume of aerosol-containing air. However, we currently do not know how exercise affects the concentration of aerosol particles in exhaled air and the overall emission of aerosol particles. Consequently, we developed a method to measure in parallel the concentration of aerosol particles in expired air, pulmonary ventilation, and aerosol particle emission at rest and during a graded exercise test to exhaustion. We used this method to test eight women and eight men in a descriptive study. We found that the aerosol particle concentration in expired air increased significantly from 56 ± 53 particles/liter at rest to 633 ± 422 particles/liter at maximal intensity. Aerosol particle emission per subject increased significantly by a factor of 132 from 580 ± 489 particles/min at rest to a super emission of 76,200 ± 48,000 particles/min during maximal exercise. There were no sex differences in aerosol particle emission, but endurance-training subjects emitted significantly more aerosol particles during maximal exercise than untrained subjects. Overall, aerosol particle emission increased moderately up to an exercise intensity of ∼2 W/kg and exponentially thereafter. Together, these data might partly explain superspreader events especially during high-intensity group exercise indoors and suggest that strong infection prevention measures are needed especially during exercise at an intensity that exceeds ∼2 W/kg. Investigations of influencing factors like airway and whole-body hydration status during exercise on aerosol particle generation are needed.

Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett's carcinoma.

BACKGROUND AND AIMS: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation. METHODS: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625-10 mg/mL); cell growth was determined on a Multiwell plate reader. RESULTS: Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls. CONCLUSIONS: Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.

Flow profiles near receding three-phase contact lines: influence of surfactants.

The dynamics of wetting and dewetting is largely determined by the velocity field near the contact lines. For water drops it has been observed that adding surfactant decreases the dynamic receding contact angle even at a concentration much lower than the critical micelle concentration (CMC). To better understand why surfactants have such a drastic effect on drop dynamics, we constructed a dedicated setup on an inverted microscope, in which an aqueous drop is held stationary while the transparent substrate is moved horizontally. Using astigmatism particle tracking velocimetry, we track the 3D displacement of the tracer particles in the flow. We study how surfactants alter the flow dynamics near the receding contact line of a moving drop for capillary numbers in the order of 10-6. Even for surfactant concentrations c far below the critical micelle concentration (c ≪ CMC) Marangoni stresses change the flow drastically. We discuss our results first in a 2D model that considers advective and diffusive surfactant transport and deduce estimates of the magnitude and scaling of the Marangoni stress from this. Modeling and experiment agree that a tiny gradient in surface tension of a few µN m-1 is enough to alter the flow profile significantly. The variation of the Marangoni stress with the distance from the contact line suggests that the 2D advection-diffusion model has to be extended to a full 3D model. The effect is ubiquitous, since surfactant is present in many technical and natural dewetting processes either deliberately or as contamination.

Effects of Vibration Training in Interstitial Lung Diseases: A Randomized Controlled Trial.

BACKGROUND: Numerous studies have reported positive effects of exercise training in patients with interstitial lung disease (ILD) on physical capacity and quality of life. However, evidence is rare on the effects of specific forms of training and further pathophysiological mechanisms in these patients. OBJECTIVES: In this multicenter study we aimed to explore the clinical effects of whole-body vibration training (WBVT) in patients with ILD on various outcome measures, including proinflammatory cytokines and myostatin. METHODS: We randomly assigned 26 patients with different forms of multidisciplinary confirmed fibrotic ILDs either to the WBVT group (n = 11; 55% male, 61 ± 14 years old, forced vital capacity 83.2 ± 29.3% predicted, 6-min walking distance [6MWD] 478 ± 79 m) performing 3 months of a standardized training (3 times per week), or to a control training group (CTG, n = 15; 60% male, 63 ± 9 years old, FVC 74.6 ± 20.5% predicted, 6MWD 455 ± 85 m) performing sham WBV training. Training in the two groups was performed on a GalileoTM vibration plate (6-20 vs. 5 Hz). The functional assessments before and after the intervention period included pulmonary function, 6MWD test, chair rise test, ultrasonographic measurement of quadriceps muscle thickness (cross-sectional area), quality of life questionnaires, and serum samples. RESULTS: We observed a significant increase in 6MWD (∆Training = 30 m [12-67], p = 0.024) and a decrease of myostatin (∆Training = -465 pg/mL [-713 to -166], p = 0.008) in the WBVT group. In contrast, no significant differences were observed in the CTG. CONCLUSIONS: The present study demonstrates that WBVT is able to significantly increase 6MWD and decrease myostatin in patients with fibrotic ILDs. Therefore, WBVT seems to be a beneficial and feasible training modality in ILD patients. Clinical Trial Registry: German Clinical Trials Registry (DRKS00012930).

Fundamental protective mechanisms of face masks against droplet infections.

Many governments have instructed the population to wear simple mouse-and-nose covers or surgical face masks to protect themselves from droplet infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in public. However, the basic protection mechanisms and benefits of these masks remain controversial. Therefore, the aim of this work is to show from a fluid physics point of view under which circumstances these masks can protect against droplet infection. First of all, we show that the masks protect people in the surrounding area quite well, since the flow resistance of the face masks effectively prevents the spread of exhaled air, e.g. when breathing, speaking, singing, coughing and sneezing. Secondly, we provide visual evidence that typical household materials used by the population to make masks do not provide highly efficient protection against respirable particles and droplets with a diameter of 0.3-2 µm as they pass through the materials largely unfiltered. According to our tests, only vacuum cleaner bags with fine dust filters show a comparable or even better filtering effect than commercial particle filtering FFP2/N95/KN95 half masks. Thirdly, we show that even simple mouse-and-nose covers made of good filter material cannot reliably protect against droplet infection in contaminated ambient air, since most of the air flows through gaps at the edge of the masks. Only a close-fitting, particle-filtering respirator offers good self-protection against droplet infection. Nevertheless, wearing simple homemade or surgical face masks in public is highly recommended if no particle filtrating respiratory mask is available. Firstly, because they protect against habitual contact of the face with the hands and thus serve as self-protection against contact infection. Secondly, because the flow resistance of the masks ensures that the air remains close to the head when breathing, speaking, singing, coughing and sneezing, thus protecting other people if they have sufficient distance from each other. However, if the distance rules cannot be observed and the risk of inhalation-based infection becomes high because many people in the vicinity are infectious and the air exchange rate is small, improved filtration efficiency masks are needed, to take full advantage of the three fundamental protective mechanisms these masks provide.

Spicae aetheroleum in uncomplicated acute bronchitis: a double-blind, randomised clinical trial.

BACKGROUND: The trial aimed to evaluate the efficacy and safety of Spicae aetheroleum (Spicae ae.), a phytomedicine obtained by steam distillation of the flowering tops of Lavandula latifolia, as compared to placebo in adult patients with acute bronchitis. METHODS: Patients with uncomplicated acute bronchitis (bronchitis severity score [BSS] ≥ 5 score points) were randomly assigned to treatment with Spicae ae. or placebo in a double-blind, parallel-group design. No additional treatment was admitted. The primary objective was the mean difference of a defined total BSS of 25% between the Spicae ae. and the placebo group after 7 days of full medication dose. Secondary endpoints included the BSS at day 10, additional signs and symptoms of bronchitis, quality of life (QoL) and safety. RESULTS: The mean decrease in BSS at day 7 and day 10 was significant with 4.79 vs. 3.20 (p < 0.005 for a 25% difference) and 6.47 vs. 4.32 (p < 0.009 for a 25% difference) score points respectively in the Spicae ae. (n = 119) vs. placebo group (n = 110). Accordingly, most additional signs and symptoms of acute bronchitis as well as the patients' QoL improved significantly with Spicae ae. as compared to placebo. In all, 258 patients were eligible for safety analysis. The treatment with Spicae ae. was well tolerated; no serious adverse events occurred. CONCLUSION: The defined objectives both for the primary and secondary endpoints have been met. The results of this study provide evidence that Spicae ae. is well tolerated, effective and superior to placebo in the symptomatic treatment of uncomplicated acute bronchitis in adult patients.

Surfactant-driven flow transitions in evaporating droplets.

An evaporating droplet is a dynamic system in which flow is spontaneously generated to minimize the surface energy, dragging particles to the borders and ultimately resulting in the so-called "coffee-stain effect". The situation becomes more complex at the droplet's surface, where surface tension gradients of different natures can compete with each other yielding different scenarios. With careful experiments and with the aid of 3D particle tracking techniques, we are able to show that different types of surfactants turn the droplet's surface either rigid or elastic, which alters the evaporating fluid flow, either enhancing the classical coffee-stain effect or leading to a total flow inversion. Our measurements lead to unprecedented and detailed measurements of the surface tension difference along the evaporating droplet's surface with good temporal and spatial resolution.

Macroscopic three-dimensional particle location using stereoscopic imaging and astigmatic aberrations.

This Letter presents a stereoscopic imaging concept for measuring the locations of particles in three-dimensional space. The method is derived from astigmatism particle tracking velocimetry (APTV), a powerful technique that is capable of determining 3D particle locations with a single camera. APTV locates particle xy coordinates with high accuracy, while the particle z coordinate has a larger location uncertainty. This is not a problem for 3D2C (i.e., three dimensions, two velocity components) measurements, but for highly three-dimensional flows, it is desirable to measure three velocity components with similar accuracy. The stereoscopic APTV approach discussed in this report has this capability. The technique employs APTV for giving an initial estimate of the particle locations. With this information, corresponding particle images on both sensors of the stereoscopic imaging system are matched. Particle locations are then determined by mapping the two particle image sensor locations to physical space. The measurement error of stereo APTV, determined by acquiring images of 1-µm DEHS particles in a 40 mm×40 mm×20 mm measurement volume in air at Δxyz→0 between two frames, is less than 0.012 mm for xy and 0.025 mm for z. This error analysis proves the excellent suitability of stereo APTV for the measurement of three-dimensional flows in macroscopic domains.

Three-dimensional location of micrometer-sized particles in macroscopic domains using astigmatic aberrations.

This Letter presents a theoretical and experimental image formation study in the presence of astigmatic aberrations. A three-dimensional, macroscopic location scheme of micrometer-sized particles for the single camera astigmatism particle tracking velocimetry (APTV) technique is introduced. Average particle z position determination errors of the technique are as low as 0.33%, with a measurement depth of 40 mm. These accuracies show APTV's ability of measuring volumetric velocity fields in macroscopic domains with limited optical access.

Enhanced particle separation through ultrasonically-induced microbubble streaming for automated size-selective particle depletion.

In this study, we present an automated method for achieving Size-Selective Particle Depletion in microchannels. This technique is notable for its label-free, sheath-free, and cost-effective attributes. It combines continuous Poiseuille flow with microbubble streaming to enable the manipulation of particles in an automatic or semi-automatic manner at periodic intervals. Larger particles are retained in proximity to the microbubble, with the option for subsequent eviction through a designated waste exit or their accumulation within a collection chamber for future analysis or manipulation. Unlike many conventional methods, our approach keeps the target particles in the vortices near the microbubble while the primary fluid flows continuously through the microchannel. Subsequently, these particles are ejected in just a few milliseconds, preserving the primary fluid and significantly reducing fluid wastage. We conducted an analysis covering multiple critical facets of the study. This included a rigorous statistical examination, flow characterization using volumetric micro PTV, high-frequency micro PTV for observing flow field transitions, evaluating the system's particle trapping capabilities across different sizes with a proprietary algorithm, and investigating the z-axis distribution of both incoming and escaped particles using volumetric micro PTV. The invaluable insights gleaned from this data played a pivotal role in refining the system and optimizing its operational parameters to achieve peak efficiency across various conditions, encompassing varying particle sizes, flow rates, and seeding densities.

Indices of airway resistance and reactance from impulse oscillometry correlate with aerosol particle emission in different age groups.

Airborne transmission of pathogens plays a major role in the spread of infectious diseases. Aerosol particle production from the lung is thought to occur in the peripheral airways. In the present study we investigated eighty lung-healthy subjects of two age groups (20-39, 60-76 years) at rest and during exercise whether lung function parameters indicative of peripheral airway function were correlated with individual differences in aerosol particle emission. Lung function comprised spirometry and impulse oscillometry during quiet breathing and an expiratory vital capacity manoeuvre, using resistance (R5) and reactance at 5 Hz (X5) as indicators potentially related to peripheral airway function. The association between emission at different ventilation rates relative to maximum ventilation and lung function was assessed by regression analysis. In multiple regression analyses including age group, only vital capacity manoeuvre R5 at 15% to 50% of end-expiratory vital capacity as well as quiet breathing X5 were independently linked to particle emission at 20% to 50% of maximum ventilation, in addition to age group. The fact that age as predictive factor was still significant, although to a lower degree, points towards further effects of age, potentially involving surface properties not accounted for by impulse oscillometry parameters.

Logarithmic boundary layers in strong Taylor-Couette turbulence.

We provide direct measurements of the boundary layer properties in highly turbulent Taylor-Couette flow up to Re=2×106) (Ta=6.2×10(12)) using high-resolution particle image velocimetry and particle tracking velocimetry. We find that the mean azimuthal velocity profile at the inner and outer cylinder can be fitted by the von Kármán log law u+=1/κ lny+ +B. The von Kármán constant κ is found to depend on the driving strength Ta and for large Ta asymptotically approaches κ≈0.40. The variance profiles of the local azimuthal velocity have a universal peak around y+≈12 and collapse when rescaled with the driving velocity (and not with the friction velocity), displaying a log dependence of y+ as also found for channel and pipe flows.

Formation of a polymer surface with a gradient of pore size using a microfluidic chip.

Here we demonstrate the generation of polymer monolithic surfaces possessing a gradient of pore and polymer globule sizes from ~0.1 to ~0.5 µm defined by the composition of two polymerization mixtures injected into a microfluidic chip. To generate the gradient, we used a PDMS microfluidic chip with a cascade micromixer with a subsequent reaction chamber for the formation of a continuous gradient film. The micromixer has zigzag channels of 400 × 680 µm(2) cross section and six cascades. The chip was used with a reversible bonding connection, realized by curing agent coating. After polymerization in the microfluidic chip the reversible bond was opened, resulting in a 450 µm thick polymer film possessing the pore size gradient. The gradient formation in the microfluidic reaction chamber was studied using microscopic laser-induced fluorescence (µLIF) and different model fluids. Formation of linear gradients was shown using the fluids of the same density by both diffusive mixing at flow rates of 0.001 mL/min and in a convective mixing regime at flow rates of 20 mL/min. By using different density fluids, formation of a two-dimensional wedge-like gradient controlled by the density difference and orientation of the microfluidic chip was observed.

Parallax correction for precise near-wall flow investigations using particle imaging.

For the basic understanding of turbulence generation in wall-bounded flows, precise measurements of the mean velocity profile and the mean velocity fluctuations very close to the wall are essential. Therefore, three techniques are established for high-resolution velocity profile measurements close to solid surfaces: (1) the nanoprobe sensor developed at Princeton University, which is a miniaturization of a classical hot-wire probe [Exp. Fluids 51, 1521 (2011)]; (2) the laser Doppler velocimetry (LDV) profile sensor, which allows measurement of the location of the particles inside the probe volume using a superposition of two fringe systems [Exp. Fluids 40, 473 (2006)]; and (3) the combination of particle image velocimetry and tracking techniques (PIV/PTV), which identify the location and velocity of submicrometer particles within the flow with digital imaging techniques [Exp. Fluids 52, 1641 (2006)]. The last technique is usually considered less accurate and precise than the other two. However, in addition to the measurement precision, the effect of the probe size, the position error, and errors due to vibrations of the model, test facility, or measurement equipment have to be considered. Taking these into account, the overall accuracy of the PTV technique can be superior, as all these effects can be compensated for. However, for very accurate PTV measurements close to walls, it is necessary to compensate the perspective error, which occurs for particles not located on the optical axis. In this paper, we outline a detailed analysis for this bias error and procedures for its compensation. To demonstrate the capability of the approach, we measured a turbulent boundary layer at Re(δ)=0.4×10(6) and applied the proposed methods.

Numerical and experimental characterization of a novel modular passive micromixer.

This paper reports a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry were analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency was quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion was assessed through the lacunarity index. The results show that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80 % at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (µLIF) technique was applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice.

The German adaptation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).

BACKGROUND: Individuals with precapillary pulmonary hypertension (PH) experience severely impaired quality of life. A disease-specific outcome measure for PH, the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was developed and validated in the UK and subsequently adapted for use in additional countries. The aim of this study was to translate and assess the reliability and validity of the CAMPHOR for German-speaking populations. METHODS: Three main adaptation stages involved; translation (employing bilingual and lay panels), cognitive debriefing interviews with patients and validation (assessment of the adaptation's psychometric properties). The psychometric evaluation included 107 patients with precapillary PH (60 females; age mean (standard deviation) 60 (15) years) from 3 centres in Austria, Germany and Switzerland. RESULTS: No major problems were found with the translation process with most items easily rendered into acceptable German. Participants in the cognitive debriefing interviews found the questionnaires relevant, comprehensive and easy to complete. Psychometric analyses showed that the adaptation was successful. The three CAMPHOR scales (symptoms, activity limitations and quality of life) had excellent test-retest reliability correlations (Symptoms = 0.91; Activity limitations = 0.91; QoL = 0.90) and internal consistency (Symptoms = 0.94; Activity limitations = 0.93; QoL = 0.94). Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the CAMPHOR scales. The CAMPHOR adaptation also showed known group validity in its ability to distinguish between participants based on perceived general health, perceived disease severity, oxygen use and NYHA classification. CONCLUSIONS: The CAMPHOR has been shown to be valid and reliable in the German population and is recommend for use in clinical practice.

High prevalence of p16 staining in malignant tumors.

p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer types is controversial. 15,783 samples from 124 different tumor types and 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. p16 was detectable in 5,292 (45.0%) of 11,759 interpretable tumors. Except from adenohypophysis in islets of Langerhans, p16 staining was largely absent in normal tissues. In cancer, highest positivity rates were observed in uterine cervix squamous cell carcinomas (94.4%), non-invasive papillary urothelial carcinoma, pTaG2 (100%), Merkel cell carcinoma (97.7%), and small cell carcinomas of various sites of origin (54.5%-100%). All 124 tumor categories showed at least occasional p16 immunostaining. Comparison with clinico-pathological data in 128 vulvar, 149 endometrial, 295 serous ovarian, 396 pancreatic, 1365 colorectal, 284 gastric, and 1245 urinary bladder cancers, 910 breast carcinomas, 620 clear cell renal cell carcinomas, and 414 testicular germ cell tumors revealed only few statistically significant associations. Comparison of human papilloma virus (HPV) status and p16 in 497 squamous cell carcinomas of different organs revealed HPV in 80.4% of p16 positive and in 20.6% of p16 negative cancers (p<0.0001). It is concluded, that a positive and especially strong p16 immunostaining is a feature for malignancy which may be diagnostically useful in lipomatous, urothelial and possibly other tumors. The imperfect association between p16 immunostaining and HPV infection with high variability between different sites of origin challenges the use of p16 immunohistochemistry as a surrogate for HPV positivity, except in tumors of cervix uteri and the penis.