Exhaled Breath Aerosol Shedding of Highly Transmissible Versus Prior Severe Acute Respiratory Syndrome Coronavirus 2 Variants.

BACKGROUND: Aerosol inhalation is recognized as the dominant mode of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Three highly transmissible lineages evolved during the pandemic. One hypothesis to explain increased transmissibility is that natural selection favors variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. We aimed to measure the infectivity and rate of SARS-CoV-2 shedding into exhaled breath aerosol (EBA) by individuals during the Delta and Omicron waves and compared those rates with those of prior SARS-CoV-2 variants from our previously published work. METHODS: Individuals with coronavirus disease 2019 (COVID-19) (n = 93; 32 vaccinated and 20 boosted) were recruited to give samples, including 30-minute breath samples into a Gesundheit-II EBA sampler. Samples were quantified for viral RNA using reverse-transcription polymerase chain reaction and cultured for virus. RESULTS: Alpha (n = 4), Delta (n = 3), and Omicron (n = 29) cases shed significantly more viral RNA copies into EBAs than cases infected with ancestral strains and variants not associated with increased transmissibility (n = 57). All Delta and Omicron cases were fully vaccinated and most Omicron cases were boosted. We cultured virus from the EBA of 1 boosted and 3 fully vaccinated cases. CONCLUSIONS: Alpha, Delta, and Omicron independently evolved high viral aerosol shedding phenotypes, demonstrating convergent evolution. Vaccinated and boosted cases can shed infectious SARS-CoV-2 via EBA. These findings support a dominant role of infectious aerosols in transmission of SARS-CoV-2. Monitoring aerosol shedding from new variants and emerging pathogens can be an important component of future threat assessments and guide interventions to prevent transmission.

Relative efficacy of masks and respirators as source control for viral aerosol shedding from people infected with SARS-CoV-2: a controlled human exhaled breath aerosol experimental study.

BACKGROUND: Tight-fitting masks and respirators, in manikin studies, improved aerosol source control compared to loose-fitting masks. Whether this translates to humans is not known. METHODS: We compared efficacy of masks (cloth and surgical) and respirators (KN95 and N95) as source control for SARS-CoV-2 viral load in exhaled breath of volunteers with COVID-19 using a controlled human experimental study. Volunteers (N = 44, 43% female) provided paired unmasked and masked breath samples allowing computation of source-control factors. FINDINGS: All masks and respirators significantly reduced exhaled viral load, without fit tests or training. A duckbill N95 reduced exhaled viral load by 98% (95% CI: 97%-99%), and significantly outperformed a KN95 (p < 0.001) as well as cloth and surgical masks. Cloth masks outperformed a surgical mask (p = 0.027) and the tested KN95 (p = 0.014). INTERPRETATION: These results suggest that N95 respirators could be the standard of care in nursing homes and healthcare settings when respiratory viral infections are prevalent in the community and healthcare-associated transmission risk is elevated. FUNDING: Defense Advanced Research Projects Agency, National Institute of Allergy and Infectious Diseases, Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, and The Flu Lab.

[Experimental and numerical investigation of fluid-particle-interactions in water]. / Experimentelle und numerische Untersuchung von Fluid-Partikel-Interaktionen in Wasser.

For the development of improved sediment transport models, the basic understanding of the interaction between the solid particle and the moving fluid (water) is important. In this article, current developments in the field of fluid-particle interaction are presented based on two research articles by Gold et al. (2023) and Worf et al. (2022). One presented in this article uses state of the art measurement methods to investigate the flow around spheres of different densities that oscillate in initially resting body of water. For the spherical pendulum a similar vortex shedding characteristic was observed for all investigated fluid density ratios (m*=ρS/ρF=1.14,14.95, density ratio between solid and fluid). A new object tracking method (DOT) is also presented, which enables temporally and spatially resolved analysis of flow structures in the fluid field. The experimental results of Gold et al. (2023) show, that vortex shedding occurs during the first period. This vortex propagates downward and eventually dissipates. Furthermore, a damping optimum of the spherical pendulum in the range of m*=2.50 was observed. Additionally, an experiment with a cylindrical pendulum with m∗=4.98 was investigated numerically utilizing an immersed boundary method. The process of creation and separation up to the dissipation of a vortex ring was described. Furthermore, this investigation by Worf et al. (2022) described the creation of tip vortices. These were connected with the development of the three-dimensional flow and added mass coefficient.

[Movement of a fluvial particle under the influence of coherent structures]. / Bewegung eines Einzelkorns unter dem Einfluss kohärenter Strukturen.

In a fundamental study the influence of coherent structures on the incipient motion of single fluvial grain was experimentally investigated. To fully characterize coherent structures, the three-dimensional velocity field must be known with high temporal resolution. Using a tr-3D PTV system (tr = time-resolved, PTV = particle tracking velocimetry) this could be achieved. The influence of hairpin vortices and counter-rotating longitudinal vortices (VLSM) on sediment transport has been postulated in several studies, but due to the missing 3D information, evidence has been lacking. In the present "Rolling Stones test series", the incipient motion of a single grain was investigated for smooth and rough beds. It could be shown for the first time that both hairpin vortices and VLSM trigger particle entrainment. Hairpin vortices could also be detected on rough beds, contrary to common hypotheses, and triggered particle movement. The long-term study should also find practical applications in the coming years and increase the accuracy of sediment transport calculations in rivers.

Electrical origin of the outbursts on io.

The outbursts seen on Jupiter's satellite Io have been described as volcanic eruptions. They may instead be the result of large electric currents flowing through hot spots on Io and causing evaporation of surface materials. A strictly periodic behavior would then be expected.

Radio method for the precise measurement of the rotation period of the Earth.

Radio interferometry with independent high-precision clocks, without a high-frequency communication channel between the stations, is now a possibility. It allows the stations to be as far apart as the earth can accommodate. This then makes the radio band from 10- to 60-centimeters wavelength the best frequency range for high-precision angular measurements, since the variability of the atmosphere is less disturbing there than in the optical band.

Apollo 11 observations of a remarkable glazing phenomenon on the lunar surface.

Some glazing is apparently due to radiation heating; it suggests a giant solar outburst in geologically recent times.

Brontides: natural explosive noises.

Episodes of explosive noises of natural origin, or brontides, have been well documented, often in association with seismic activity and in a few cases as precursors to major earthquakes. Ground-to-air acoustic transmission from shallow earthquakes can account for many of these episodes, but not for all, and other causes, such as the sudden eruption of gas from high-pressure sources in the ground may at times have been responsible. Confusion with distant thunder or artillery at times of anomalous sound propagation complicates the analysis, and more recently the greatly increased frequency of artificial explosive noises and sonic booms has tended to mask the recognition of natural brontides.

Luna 9 pictures: implications.

Evidence from Luna 9 does not preclude the possibility that the moon may have a surface made up largely of very fine rock particles. The degree to which they attach to each other and the resulting firmness of the ground cannot yet be closely estimated.

Apollo 12 seismic signal: indication of a deep layer of powder.

The seismic signal caused by the Apollo 12 lunar module is interpreted in terms of propagation between source and receiver through a layer of powder in which sound velocity increases with depth. This increase, which is due to compaction, extends over several kilometers and leads to a concentration of seismic waves toward the surface. Computer simulations with the use of ray acoustics and on the assumption of a randomly undulating lunar surface approximate well the observed signal. Seismic amplitudes are greatly enhanced in such a medium compared to solid rock, so that the observed signal requires less power to be transmitted than previously estimated.

Optical and high-frequency electrical properties of the lunar sample.

Reflectivity and polarization laws for the powder sample and its spectrum are close to the mean for the lunar maria. Solid samples show a marked absorption feature at 1 micron. The low albedo appears to be due to a surface coating on dust grains rather than to volume absorption. The high-frequency electrical properties resemble those of a fine powder made from typical dense terrestrial rocks and are consistent with previous estimates from ground-based radar observations. The differential mass spectrum is almost constant from 100 micron particles down to 0.1 micron particles; most particles are smaller than 0.3 micron. Their shapes disclose a variety of processes of generation.

Impact of fractures on quality of life in patients with osteoporosis: a US cross-sectional survey.

Objective: To evaluate the impact of osteoporosis-related fractures on health-related quality of life (HRQoL). Methods: Data were obtained from the 2016 Adelphi US Osteoporosis Disease Specific Programme™, a cross-sectional survey of physicians and their male and female patients with osteoporosis. Patient-reported outcomes (PRO) measures included the European Quality of Life 5 Domains (EQ-5D), European Quality of Life Visual Analog Scale (EQ-VAS), and Osteoporosis Assessment Questionnaire short-version (OPAQ-SV; physical, emotional, and symptom domains). Associations between PRO scores and the number and site of fractures were evaluated using ANOVA. Multivariate analyses were conducted using linear regression. Results: Physicians provided records for 1848 patients with osteoporosis. Of these, 981 (53.1%) completed the patient survey, data for the number of fractures were available for 935/981 (95.3%), and 185/935 (19.8%) had a history of fracture. Experiencing fractures significantly influenced scores on all PRO measures (p < .0001). Hip and spine fractures were associated with the greatest reduction in most PRO scores. The number of fractures, age, body mass index, and Charlson Comorbidity Index (CCI) were significantly associated with PRO measures (p < .05) in multivariate analyses. In patients with a fracture, fracture site, CCI, gender (EQ-5D and EQ-VAS), and age (OPAQ-SV physical only) were significantly associated with PRO measures. Conclusions: In patients with osteoporosis, fractures are associated with lower HRQoL and lower overall health status. Fracture history, fracture site, age, and comorbidity burden significantly influence HRQoL in individuals with osteoporosis. These data suggest the need for interventions to reduce the risk of fractures in patients with osteoporosis.

Diet-Induced Obesity and Its Differential Impact on Periodontal Bone Loss.

Obesity is associated with abnormal lipid metabolism and impaired bone homeostasis. The aim of our study was to investigate the impact of specific elevated fatty acid (FA) levels on alveolar bone loss in a Porphyromonas gingivalis-induced model of periodontal disease and to analyze underlying cellular mechanisms in bone-resorbing osteoclasts and bone-forming osteoblasts in mice. Four-week-old male C57BL/6 mice were randomly divided in groups and subjected to a palmitic acid (PA)- or oleic acid (OA)-enriched high-fat diet (HFD) (20% of calories from FA) or a normal caloric diet (C group) (10% of calories from FA) for 16 wk. Starting at week 10, mice were infected orally with P. gingivalis (W50) or placebo to induce alveolar bone loss. Animals were sacrificed, and percentage fat, serum inflammation (tumor necrosis factor [TNF]-α), and bone metabolism (osteocalcin [OC], carboxy-terminal collagen crosslinks [CTX], and N-terminal propeptides of type I procollagen [P1NP]) markers were measured. Osteoblasts and osteoclasts were cultured in the presence of elevated PA or OA levels and exposed to P. gingivalis. Animals on FA-enriched diets weighed significantly more compared with animals on a normal caloric diet (P < 0.05). Both obese groups had similar percentages of fat (P = nonsignificant); however, alveolar bone loss was significantly greater in animals that were on the PA-enriched HFD (P < 0.05). TNF-α levels were highest in the PA group (P < 0.001) and increased in all groups in response to P. gingivalis inoculation (P < 0.01), whereas bone remodeling markers OC, CTX, and P1NP were lowest in the PA group (P < 0.001) and highest in the C group. Bacterial challenge decreased bone metabolism markers in all groups (P < 0.01). Further, osteoclasts showed an augmented inflammatory response to P. gingivalis in the presence of hyperlipidemic PA levels as opposed to OA cultures, which responded similarly to controls. These findings indicate that the specific FA profile of diet rather than weight gain and obesity alone modulates bone metabolism and can therefore influence alveolar bone loss.

Mediation of the in vitro cytotoxicity of green and black tea polyphenols by cobalt chloride.

The effects of Co2+ (as CoCl2) on the cytotoxicity of green tea polyphenol (GTP) and black tea polyphenol (BTP) extracts towards proliferation of immortalized human gingival epithelial-like S-G cells were studied. The 24 h potencies of GTP and BTP extracts, as determined with the neutral red (NR) cell viability assay, were greatly reduced in the presence of 250, but not of 50, microM Co2+. The cytotoxicities of the GTP and BTP extracts were due, in part, to their generation of hydrogen peroxide (H2O2) in the cell culture medium (DMEM). Progressively increasing the concentration of Co2+ in the tea polyphenol-amended cell culture medium resulted in a lowering of the level of H2O2. The cytotoxicity of freshly added H2O2 to S-G cells was abolished in the presence of 250 microM Co2+ and the level of freshly added H2O2 to cell culture medium was progressively lowered as the concentration of Co2+ was increased. Apparently, under the conditions of these studies, the decreases in the cytotoxicity of GTP and BTP extracts in the presence of CoCl2 were due to the rapid catalytic decomposition by Co2+ of the H2O2 generated in the tea polyphenol-amended cell culture medium.

Time-dependent disruptive effects of apomorphine and alpha-methyl-p-tyrosine on development of morphine tolerance.

In rats the development of one-trial tolerance to the analgesic action of i.p. administered morphine is disrupted by the postadministration of apomorphine (30 mg/kg at 5 min but not at 3 h) or alpha-methyl-p-tyrosine (200 mg/kg at 5 min and 3 h but not at 12 h). Diethyldithiocarbamate or propranol has no disruptive effect. It is suggested that development of tolerance to the analgesic effects of morphine is mediated by sequential time-dependent biochemical processes.

Cross-linking of gelatin capsules and its relevance to their in vitro-in vivo performance.

The present review deals with the chemistry of gelatin cross-linking under conditions that are relevant to pharmaceutical situations. Mechanistic rationalizations are offered to explain gelatin cross-linking under "stress" conditions. These include elevated temperature and high humidity conditions. In addition, the chemical interactions between gelatin and aldehydes, such as formaldehyde and other formulation excipients, are discussed. The literature on the in vitro and in vivo dissolution and bioavailability of a drug from stressed gelatin capsules and gelatin-coated tablets is reviewed. Cross-linking phenomena, occurring in stressed hard gelatin capsules and gelatin-coated tablets, could cause considerable changes in the in vitro dissolution profiles of drugs. However, in a few cases, the bioavailability of the drug from the stressed capsules is not significantly altered when compared to that obtained from freshly packed capsules. It is concluded that, as with other drug-delivery systems, careful attention should be paid to the purity and chemical reactivity of all excipients that are to be encapsulated in a gelatin shell. It is suggested that in vitro dissolution tests of hard gelatin-containing dosage forms be conducted in two stages, one in a dissolution medium without enzymes and secondly in dissolution media containing enzymes (pepsin at pH 1.2 or pancreatin at pH 7.2, representing gastric and intestinal media, respectively) prior to in vivo evaluation. Such in vitro tests may constitute a better indication of the in vivo behavior of gelatin-encapsulated formulations. Furthermore, testing for contamination with formaldehyde as well as low molecular weight aldehydes should be a standard part of excipient evaluation procedures.

Effective desensitization protocol to paclitaxel following hypersensitivity reaction.

The objective of this paper is to describe our experience with a desensitization protocol to paclitaxel using the original paclitaxel solution in patients following severe hypersensitivity reactions. A retrospective review of 75 consecutive patients with ovarian cancer who received intravenous paclitaxel-based chemotherapy between January 1996 and May 1998 at the Gynecologic Oncology Unit at Meir Hospital-Sapir Medical Center, Kfar-Saba, Israel. All patients who developed a hypersensitivity reaction to paclitaxel were treated with a desensitization protocol. The protocol included serial 10-fold dilutions (up to 1:100,000) of the actual paclitaxel infusate, delivered in successive volumes of 1, 2, 4, and 8 ml. These escalating doses of paclitaxel were given intravenously at 15-min intervals for each dilution. Following administration of the last diluted dose, the patient received a 1-ml dose of the undiluted solution. If no side effects were recorded, the rest of the actual dose was delivered at a 3-h infusion rate. Vital signs were monitored and recorded throughout the course of treatment. Six patients with a previous paclitaxel-associated hypersensitivity reaction were successfully treated with the desensitization protocol. In conclusion, we demonstrate that the desensitization protocol is feasible and safe without compromising cytotoxic activity. Our results show that this strategy is a reasonable choice in this clinical setting and potentially avoids paclitaxel-based regimen interruption.