A novel multifunctional radioprotective strategy using P7C3 as a countermeasure against ionizing radiation-induced bone loss.

Radiotherapy is a critical component of cancer care but can cause osteoporosis and pathological insufficiency fractures in surrounding and otherwise healthy bone. Presently, no effective countermeasure exists, and ionizing radiation-induced bone damage continues to be a substantial source of pain and morbidity. The purpose of this study was to investigate a small molecule aminopropyl carbazole named P7C3 as a novel radioprotective strategy. Our studies revealed that P7C3 repressed ionizing radiation (IR)-induced osteoclastic activity, inhibited adipogenesis, and promoted osteoblastogenesis and mineral deposition in vitro. We also demonstrated that rodents exposed to clinically equivalent hypofractionated levels of IR in vivo develop weakened, osteoporotic bone. However, the administration of P7C3 significantly inhibited osteoclastic activity, lipid formation and bone marrow adiposity and mitigated tissue loss such that bone maintained its area, architecture, and mechanical strength. Our findings revealed significant enhancement of cellular macromolecule metabolic processes, myeloid cell differentiation, and the proteins LRP-4, TAGLN, ILK, and Tollip, with downregulation of GDF-3, SH2B1, and CD200. These proteins are key in favoring osteoblast over adipogenic progenitor differentiation, cell matrix interactions, and shape and motility, facilitating inflammatory resolution, and suppressing osteoclastogenesis, potentially via Wnt/ß-catenin signaling. A concern was whether P7C3 afforded similar protection to cancer cells. Preliminarily, and remarkably, at the same protective P7C3 dose, a significant reduction in triple-negative breast cancer and osteosarcoma cell metabolic activity was found in vitro. Together, these results indicate that P7C3 is a previously undiscovered key regulator of adipo-osteogenic progenitor lineage commitment and may serve as a novel multifunctional therapeutic strategy, leaving IR an effective clinical tool while diminishing the risk of adverse post-IR complications. Our data uncover a new approach for the prevention of radiation-induced bone damage, and further work is needed to investigate its ability to selectively drive cancer cell death.

The Effect of Omega-9 on Bone Viscoelasticity and Strength in an Ovariectomized Diet-Fed Murine Model.

Few studies have investigated the effect of a monosaturated diet high in ω-9 on osteoporosis. We hypothesized that omega-9 (ω-9) protects ovariectomized (OVX) mice from a decline in bone microarchitecture, tissue loss, and mechanical strength, thereby serving as a modifiable dietary intervention against osteoporotic deterioration. Female C57BL/6J mice were assigned to sham-ovariectomy, ovariectomy, or ovariectomy + estradiol treatment prior to switching their feed to a diet high in ω-9 for 12 weeks. Tibiae were evaluated using DMA, 3-point-bending, histomorphometry, and microCT. A significant decrease in lean mass (p = 0.05), tibial area (p = 0.009), and cross-sectional moment of inertia (p = 0.028) was measured in OVX mice compared to the control. A trend was seen where OVX bone displayed increased elastic modulus, ductility, storage modulus, and loss modulus, suggesting the ω-9 diet paradoxically increased both stiffness and viscosity. This implies beneficial alterations on the macro-structural, and micro-tissue level in OVX bone, potentially decreasing the fracture risk. Supporting this, no significant differences in ultimate, fracture, and yield stresses were measured. A diet high in ω-9 did not prevent microarchitectural deterioration, nevertheless, healthy tibial strength and resistance to fracture was maintained via mechanisms independent of bone structure/shape. Further investigation of ω-9 as a therapeutic in osteoporosis is warranted.

A novel approach for the prevention of ionizing radiation-induced bone loss using a designer multifunctional cerium oxide nanozyme.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

Changes in interstitial fluid flow, mass transport and the bone cell response in microgravity and normogravity.

In recent years, our scientific interest in spaceflight has grown exponentially and resulted in a thriving area of research, with hundreds of astronauts spending months of their time in space. A recent shift toward pursuing territories farther afield, aiming at near-Earth asteroids, the Moon, and Mars combined with the anticipated availability of commercial flights to space in the near future, warrants continued understanding of the human physiological processes and response mechanisms when in this extreme environment. Acute skeletal loss, more severe than any bone loss seen on Earth, has significant implications for deep space exploration, and it remains elusive as to why there is such a magnitude of difference between bone loss on Earth and loss in microgravity. The removal of gravity eliminates a critical primary mechano-stimulus, and when combined with exposure to both galactic and solar cosmic radiation, healthy human tissue function can be negatively affected. An additional effect found in microgravity, and one with limited insight, involves changes in dynamic fluid flow. Fluids provide the most fundamental way to transport chemical and biochemical elements within our bodies and apply an essential mechano-stimulus to cells. Furthermore, the cell cytoplasm is not a simple liquid, and fluid transport phenomena together with viscoelastic deformation of the cytoskeleton play key roles in cell function. In microgravity, flow behavior changes drastically, and the impact on cells within the porous system of bone and the influence of an expanding level of adiposity are not well understood. This review explores the role of interstitial fluid motion and solute transport in porous bone under two different conditions: normogravity and microgravity.

The effect of relative air humidity on the evaporation timescales of a human sneeze.

The present paper investigates droplet and aerosol emission from the human respiratory function by numerical and experimental methods, which is analyzed at the worst-case scenario, a violent sneeze without a face covering. The research findings develop the understanding of airborne disease transmission relevant to COVID-19, its recent variants, and other airborne pathogens. A human sneeze is studied using a multiphase Computational Fluid Dynamics (CFD) model using detached eddy simulation coupled to the emission of droplets that break up, evaporate, and disperse. The model provides one of the first experimental benchmarks of CFD predictions of a human sneeze event. The experiments optically capture aerosols and droplets and are processed to provide spatiotemporal data to validate the CFD model. Under the context of large random uncertainty, the studies indicate the reasonable correlation of CFD prediction with experimental measurements using velocity profiles and exposure levels, indicating that the model captures the salient details relevant to pathogen dispersion. Second, the CFD model was extended to study the effect of relative humidity with respect to the Wells curve, providing additional insight into the complexities of evaporation and sedimentation characteristics in the context of turbulent and elevated humidity conditions associated with the sneeze. The CFD results indicated correlation with the Wells curve with additional insight into features, leading to non-conservative aspects associated with increased suspension time. These factors are found to be associated with the combination of evaporation and fluid-structure-induced suspension. This effect is studied for various ambient air humidity levels and peaks for lower humidity levels, indicating that the Wells curve may need a buffer in dry climates. Specifically, we find that the increased risk in dry climates may be up to 50% higher than would be predicted using the underlying assumptions in Wells' model.

Omega-9 Modifies Viscoelasticity and Augments Bone Strength and Architecture in a High-Fat Diet-Fed Murine Model.

The influence of diet on the development of osteoporosis is significant and not fully understood. This study investigated the effect of diets of varying lipid profiles and ω-3, ω-6 and ω-9 composition on the structural and mechanical properties of bone. The hypothesis studied was that a diet high in saturated fat would induce osteoporosis and produce an overall increased detrimental bony response when compared with a diet high in unsaturated ω-6, or ω-9. Male C57BL/6J mice were fed either a control diet, 50:50 mix (saturated:unsaturated) high in ω-9 (HFD50:50), a diet high in saturated fat (HSF) or a polyunsaturated fat diet high in ω-6 (PUFA) over an 8-week duration. Tibiae were retrieved and evaluated using DMA, 3-point-bending, histomorphometry, and microCT. Mice fed a HSF diet displayed key features characteristic of osteoporosis. The loss tangent was significantly increased in the HFD50:50 diet group compared with control (p = 0.016) and PUFA-fed animals (p = 0.049). HFD50:50-fed mice presented with an increased viscous component, longer tibiae, increased loss modulus (p = 0.009), and ultimate stress, smaller microcracks (p < 0.001), and increased trabecular width (p = 0.002) compared with control animals. A diet high in ω-9 resulted in an overall superior bone response and further analysis of its role in bone health is warranted.

Human Research Study of Particulate Propagation Distance From Human Respiratory Function.

BACKGROUND: Airborne viral pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be encapsulated and transmitted through liquid droplets/aerosols formed during human respiratory events. METHODS: The number and extent of droplets/aerosols at distances between 1 and 6 ft (0.305-1.829 m) for a participant wearing no face covering, a cotton single-layer cloth face covering, and a 3-layer disposable face covering were measured for defined speech and cough events. The data include planar particle imagery to illuminate emissions by a light-sheet and local aerosol/droplet probes taken with phase Doppler interferometry and an aerodynamic particle sizer. RESULTS: Without face coverings, droplets/aerosols were detected up to a maximum of 1.25 m (4.1ft ±â€…0.22-0.28 ft) during speech and up to 1.37 m (4.5ft ±â€…0.19-0.33 ft) while coughing. The cloth face covering reduced maximum axial distances to 0.61 m (2.0 ft ±â€…0.11-0.15 ft) for speech and to 0.67 m (2.2 ft ±â€…0.02-0.20 ft) while coughing. Using the disposable face covering, safe distance was reduced further to 0.15 m (0.50 ft ±â€…0.01-0.03 ft) measured for both emission scenarios. In addition, the use of face coverings was highly effective in reducing the count of expelled aerosols. CONCLUSIONS: The experimental study indicates that 0.914 m (3 ft) physical distancing with face coverings is equally as effective at reducing aerosol/droplet exposure as 1.829 m (6 ft) with no face covering.

SARS-CoV-2 transmission in classroom settings: Effects of mitigation, age, and Delta variant.

Traditional, in-person classroom settings have been limited during the COVID-19 pandemic due to their potential to transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among students, teachers, and other educational workers. Using computational fluid dynamics simulations, mitigation strategies that span approaches using face coverings, various ventilation schemes, air purifiers/cleaners, and desk shields are systematically evaluated in thermally controlled classrooms. Individually, face coverings and source control were the most effective, which was followed by well-designed ventilation systems. The use of desk shields was also studied and appeared to be ineffective. The best mitigation approach is shown to be through multiple measures-using face coverings and ventilation systems combined with air purifiers. The studies were extended to elementary schools and consider Delta variants of SARS-CoV-2. In elementary settings, the reduced pulmonary and viral emission rates of small children are observed to drive reduced transmission rates, to values even lower than those observed with several mitigation methods for classrooms with adults. The Delta variant, with adults, was evaluated by considering an increase in quanta and indicated higher transmission probabilities. These increases are levels that are controllable by increasing the mitigation methods. Results indicate several plans of action for schools to return to in-person schooling in the context of age and new variants.

Stopping the COVID-19 pandemic in dental offices: A review of SARS-CoV-2 transmission and cross-infection prevention.

Due to the essential role of dentists in stopping the COVID-19 pandemic, the purpose of this review is to help dentists to detect any weaknesses in their disinfection and cross-contamination prevention protocols, and to triage dental treatments to meet the needs of patients during the pandemic. We used PRISMA to identify peer-reviewed publications which supplemented guidance from the center for disease control about infection control and guidelines for dentists. Dentists must triage dental treatments to meet the needs of patients during the pandemic. The ongoing pandemic has changed the practice of dentistry forever, the changes make it more cumbersome, time-consuming, and costly due to the possible pathways of transmission and mitigation steps needed to prevent the spread of COVID-19. Dental chairside rapid tests for SARS-CoV-2 are urgently needed. Until then, dentists need to screen patients for COVID-19 even though 75% of people with COVID-19 have no symptoms. Despite the widespread anxiety and fear of the devastating health effects of COVID-19, only 61% of dentists have implemented a change to their treatment protocols. As an urgent matter of public health, all dentists must identify the additional steps they can take to prevent the spread of COVID-19. The most effective steps to stop the pandemic in dental offices are to; vaccinate all dentists, staff, and patients; triage dental treatments for patients, separate vulnerable patients, separate COVID-19 patients, prevent cross-contamination, disinfect areas touched by patients, maintain social distancing, and change personal protective equipment between patients.

Effect of saliva fluid properties on pathogen transmissibility.

With an increasing body of evidence that SARS-CoV-2 is an airborne pathogen, droplet character formed during speech, coughs, and sneezes are important. Larger droplets tend to fall faster and are less prone to drive the airborne transmission pathway. Alternatively, small droplets (aerosols) can remain suspended for long time periods. The small size of SARS-CoV-2 enables it to be encapsulated in these aerosols, thereby increasing the pathogen's ability to be transmitted via airborne paths. Droplet formation during human respiratory events relates to airspeed (speech, cough, sneeze), fluid properties of the saliva/mucus, and the fluid content itself. In this work, we study the fluidic drivers (fluid properties and content) and their influence on factors relating to transmissibility. We explore the relationship between saliva fluid properties and droplet airborne transmission paths. Interestingly, the natural human response appears to potentially work with these drivers to mitigate pathogen transmission. In this work, the saliva is varied using two approaches: (1) modifying the saliva with colloids that increase the viscosity/surface tension, and (2) stimulating the saliva content to increased/decreased levels. Through modern experimental and numerical flow diagnostic methods, the character, content, and exposure to droplets and aerosols are all evaluated. The results indicate that altering the saliva properties can significantly impact the droplet size distribution, the formation of aerosols, the trajectory of the bulk of the droplet plume, and the exposure (or transmissibility) to droplets. High-fidelity numerical methods used and verify that increased droplet size character enhances droplet fallout. In the context of natural saliva response, we find previous studies indicating natural human responses of increased saliva viscosity from stress and reduced saliva content from either stress or illness. These responses both favorably correspond to reduced transmissibility. Such a finding also relates to potential control methods, hence, we compared results to a surgical mask. In general, we find that saliva alteration can produce fewer and larger droplets with less content and aerosols. Such results indicate a novel approach to alter SARS-CoV-2's transmission path and may act as a way to control the COVID-19 pandemic, as well as influenza and the common cold.

Estimating COVID-19 exposure in a classroom setting: A comparison between mathematical and numerical models.

The COVID-19 pandemic has driven numerous studies of airborne-driven transmission risk primarily through two methods: Wells-Riley and computational fluid dynamics (CFD) models. This effort provides a detailed comparison of the two methods for a classroom scenario with masked habitants and various ventilation conditions. The results of the studies concluded that (1) the Wells-Riley model agrees with CFD results without forced ventilation (6% error); (2) for the forced ventilation cases, there was a significantly higher error (29% error); (3) ventilation with moderate filtration is shown to significantly reduce infection transmission probability in the context of a classroom scenario; (4) for both cases, there was a significant amount of variation in individual transmission route infection probabilities (up to 220%), local air patterns were the main contributor driving the variation, and the separation distance from infected to susceptible was the secondary contributor; (5) masks are shown to have benefits from interacting with the thermal plume created from natural convection induced from body heat, which pushes aerosols vertically away from adjacent students.