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At least 181 records · Page 10

Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

Goodwin, T. J.↗

Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

Goodwin, Thomas J.↗

Integration of Dust Prediction Systems and Vegetation Phenology to Track Pollen for Asthma Alerts in Public Health

Pollen can be transported great distances. Van de Water et. al., 2003 reported Juniperus pollen, a significant aeroallergen was transported 200-600 km. Hence local observations of plant phenology may not be consistent with the timing and source of pollen collected by pollen sampling instruments. The DREAM (Dust REgional Atmospheric Model, Yin 2007) is a verified model for atmospheric dust transport modeling using MODIS data products to identify source regions and quantities of dust (Yin 2007). The use of satellite data products for studying phenology is well documented (White and Nemani 2006). We are modifying the DREAM model to incorporate pollen transport. The linkages already exist with DREAM through PHAiRS (Public Health Applications in remote Sensing) to the public health community. This linkage has the potential to fill this data gap so that health effects of pollen can better be tracked for linkage with health outcome data including asthma, respiratory effects, myocardial infarction, and lost work days. DREAM is based on the SKIRON/Eta modeling system and the Eta/NCEP regional atmospheric model. The dust modules of the entire system incorporate the state of the art parameterizations of all the major phases of the atmospheric dust life such as production, diffusion, advection, and removal. These modules also include effects of the particle size distribution on aerosol dispersion. The dust production mechanism is based on the viscous/turbulent mixing, shear-free convection diffusion, and soil moisture. In addition to these sophisticated mechanisms, very high resolution databases, including elevation, soil properties, and vegetation cover are utilized. The DREAM model was modified to use pollen sources instead of dust (PREAM). Pollen release will be estimated based on satellite-derived phenology of Juniperus spp. communities. The MODIS surface reflectance product (MOD09) will provide information on the start of the plant growing season, growth stage, peak greenness, dry-down and pollen release. Ground based observational records of pollen release timing and quantities will be used as verification. Techniques developed using MOD09 surface reflectance products will be directly applicable to the next generation sensors such as VIIRS. The resulting deterministic model for predicting and simulating pollen emission and downwind concentration to study details of phenology and meteorology and their dependencies. This information will be used to support the Centers for Disease Control and Prevention (CDC)'s National Environmental Public Health Tracking Program (EPHT) and the State of New Mexico environmental public health decision support for asthma and allergies alerts

Luvall, Jeffrey C.↗

Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

This article presents selected findings obtained with Holter monitoring from two crew members of the expedition, performed during a 175-day space mission on board orbital space station "MIR." Using mathematical processing of daily cardiointervals files, 5-minute sections of records were analyzed consecutively. Then, the average daily values of indices, the average-per-every-eight-hours values (morning, evening, night) and mean values per hour were computed. The results of analysis showed that prolonged exposure of man to microgravity conditions leads to important functional alteration in human neuroautonomic regulatory mechanisms. Both crew members had significant increase of heart rate, the rise of stress index, the decrease in power of the spectrum in the range of respiratory sinus arrhythmia. These marked signs of activation of the sympathetic section of the vegetative nervous system showed individual variations. The analysis of the daily collection of cardiointervals with Holter monitoring allows us to understand and forecast the functional feasibilities of the human organism under a variety of stress conditions associated with acute and chronic microgravity exposure.

manned↗

Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3–4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.

60 APPLIED LIFE SCIENCES↗

Medical technology advances from space research

Details of medical research and development programs, particularly an integrated medical laboratory, as derived from space technology are given. The program covers digital biotelemetry systems, automatic visual field mapping equipment, sponge electrode caps for clinical electroencephalograms, and advanced respiratory analysis equipment. The possibility of using the medical laboratory in ground based remote areas and regional health care facilities, as well as long duration space missions is discussed.

Pool, S. L.↗

Rapid System to Quantitatively Characterize the Airborne Microbial Community

Bioaerosols have been linked to a wide range of different allergies and respiratory illnesses. Currently, microorganism culture is the most commonly used method for exposure assessment. Such culture techniques, however, generally fail to detect between 90-99% of the actual viable biomass. Consequently, an unbiased technique for detecting airborne microorganisms is essential. In this Phase II proposal, a portable air sampling device his been developed for the collection of airborne microbial biomass from indoor (and outdoor) environments. Methods were evaluated for extracting and identifying lipids that provide information on indoor air microbial biomass, and automation of these procedures was investigated. Also, techniques to automate the extraction of DNA were explored.

Macnaughton, Sarah J.↗

Modeling of Lunar Dust Contamination Due to Plume Impingement

During the Apollo missions it became apparent that lunar dust was a significant hazard. Problems included: surface obscuration during landing sequence; abrasion damage to gouge faces and helmet visors; mechanism clogging; development of space suit pressurization leaks; loss of radiator heat rejection capabilities to the point where vulnerable equipment exceeded maximum survival temperature ratings; temporary vision and respiratory problems within the Apollo Lunar Module (LM). NASA Constellation Program features many system-level components, including the Altair Lunar Lander. Altair to endure longer periods at lunar surface conditions: Apollo LM, about three days; Altair, over seven months. Program managers interested in plume-generated dust transport onto thermal control surface radiators of the first Altair created by its own landing operations.

Woronowicz, Michael↗

Hardware-in-Loop Modules for Testing Automated Ventilator Controllers

Automated ventilator controllers have the potential to simplify oxygen and carbon dioxide management for trauma. In the pre-hospital or military medicine environment, trauma care can be required for prolonged periods by personnel with limited ventilator management training. As such, there is a need for closed-loop control systems that can adapt ventilator management to a complex, ever-changing medical environment. Here, we present a novel hardware-in-loop test platform for the independent troubleshooting and evaluation of oxygen and carbon dioxide automated ventilator management capabilities. The oxygen management system provides an analogue blood oxygen signal that is responsive to the fraction of inspired oxygen and the peak inspiratory pressure ventilator settings. A tested oxygenation controller successfully reached the target oxygen saturation within 5 min. The carbon dioxide removal system integrates with commercial ventilator technology and mimics carbon dioxide generation, lung compliance, and airway resistance while providing an end-tidal carbon dioxide level that is responsive to changes in the tidal volume and respiratory rate settings. A test mechanical ventilator controller was able to regulate EtCO2 regardless of the starting value within 10 min. This highlights the system’s functionality and provides proof-of-concept demonstrations for how the hardware-in-loop test platforms can be used for evaluating closed-loop controller technologies.

Berard, David (ORCID:0000000322863846)↗

The human respiratory gate

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

Review↗

Environmental Public Health Tracking: Health and Environment Linked for Information Exchange-Atlanta (HEXIX-Atlanta: A cooperative Program Between CDC and NASA for Development of an Environmental Public Health Tracking Network in the Atlanta Metropolitan Area

The Centers for Disease Control and Prevention (CDC) is coordinating HELIX- Atlanta to provide information regarding the five-county Metropolitan Atlanta Area (Clayton, Cobb, DeKalb, Fulton, and Gwinett) via a network of integrated environmental monitoring and public health data systems so that all sectors can take action to prevent and control environmentally related health effects. The HELIX-Atlanta Network is a tool to access interoperable information systems with optional information technology linkage functionality driven by scientific rationale. HELIX-Atlanta is a collaborative effort with local, state, federal, and academic partners, including the NASA Marshall Space Flight Center. The HELIX-Atlanta Partners identified the following HELIX-Atlanta initial focus areas: childhood lead poisoning, short-latency cancers, developmental disabilities, birth defects, vital records, respiratory health, age of housing, remote sensing data, and environmental monitoring, HELIX-Atlanta Partners identified and evaluated information systems containing information on the above focus areas. The information system evaluations resulted in recommendations for what resources would be needed to interoperate selected information systems in compliance with the CDC Public Health Information Network (PHIN). This presentation will discuss the collaborative process of building a network that links health and environment data for information exchange, including NASA remote sensing data, for use in HELIX-Atlanta.

Quattrochi, Dale A.↗

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and "Braslet-M" Occlusion Cuffs

Recent advances in remotely guided imaging techniques on ISS allow the acquisition of high quality ultrasound data using crewmember operators with no medical background and minimal training. However, ongoing efforts are required to develop and validate methodology for complex imaging protocols to ensure their repeatability, efficiency, and suitability for use aboard the ISS. This Station Developmental Test Objective (SDTO) tests a cardiovascular evaluation methodology that takes advantage of the ISS Ultrasound capability, the Braslet-M device, and modified respiratory maneuvers (Valsalva and Mueller), to broaden the spectrum of anatomical and functional information on human cardiovascular system during long-duration space missions. The proposed methodology optimizes and combines new and previously demonstrated methods, and is expected to benefit medically indicated assessments, operational research protocols, and data collections for science. Braslet-M is a current Russian operational countermeasure that compresses the upper thigh to impede the venous return from lower extremities. The goal of the SDTO is to establish and validate a repeatable ultrasound-based methodology for the assessment of a number of cardiovascular criteria in microgravity. Braslet-M device is used as a means to acutely alter volume distribution while focused ultrasound measurements are performed. Modified respiratory maneuvers are done upon volume manipulations to record commensurate changes in anatomical and functional parameters. The overall cardiovascular effects of the Braslet-M device are not completely understood, and although not a primary objective of this SDTO, this effort will provide pilot data regarding the suitability of Braslet-M for its intended purpose, effects, and the indications for its use.

Bogomolov, V. V.↗

Transfer function analysis of the autonomic response to respiratory activity during random interval breathing

We report a new method for the noninvasive characterization of the frequency response of the autonomic nervous system (ANS) in mediating fluctuations in heart rate (HR). The approach entails computation of the transfer function magnitude and phase between instantaneous lung volume and HR. Broad band fluctuations in lung volume were initiated when subjects breathed on cue to a sequence of beeps spaced randomly in time. We studied 10 subjects in both supine and standing positions. The transfer function, averaged among all the subjects, showed systematic differences between the two postures, reflecting the differing frequency responses of the sympathetic and parasympathetic divisions of the ANS.

Non-NASA Center↗

Health requirements for advanced coal extraction systems

Health requirements were developed as long range goals for future advanced coal extraction systems which would be introduced into the market in the year 2000. The goal of the requirements is that underground coal miners work in an environment that is as close as possible to the working conditions of the general population, that they do not exceed mortality and morbidity rates resulting from lung diseases that are comparable to those of the general population, and that their working conditions comply as closely as possible to those of other industries as specified by OSHA regulations. A brief technique for evaluating whether proposed advanced systems meet these safety requirements is presented, as well as a discussion of the costs of respiratory disability compensation.

Zimmerman, W. F.↗

Cardiac and Vascular Function in Bedrested Volunteers: Effects of Artificial Gravity Training

Cardiovascular effects of an artificial gravity (AG) countermeasure on deconditioned male volunteers were studied. In two groups of men we measured cardiovascular parameters at rest and in response to 30 minutes of 80 deg. head up tilt (HUT) before, at the end of, and four days following 21 days of 6 deg. head down bed rest (HDBR). One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of AG training on the Johnson Space Center short radius centrifuge. Cardiovascular parameters measured included heart rate, blood pressure, stroke volume, cardiac output, peripheral vascular resistance, plasma volume shifts, and vasoactive hormones. Untrained subjects exhibited shorter tilt survival (on average 8 minutes shorter) compared to trained subjects. By the end of bed rest, mean heart rate (MHR) was elevated in both groups (both supine and during tilt). In addition, treated subjects demonstrated lower, tilt-induced, increases in MHR four days following HDBR, indicating a more rapid return to pre bed rest conditions. Results from an index of autonomic balance (percentage of MHR spectral power in the respiratory frequency range) in control of heart rate are consistent with the interpretation that parasympathetic nervous system withdrawal was responsible for both tilt- and bed rest-induced increases in MHR. Our data support our pre-study hypothesis that AG treatment would lessen cardiovascular effects of deconditioning in bed rested men and suggest that AG should be further pursued as a space flight countermeasure.

Meng, M.↗

Building hypotheses to understand the synergistic effects of heat and pollution exposure in a changing climate

The increasing intensity, frequency, and duration of extreme weather events due to climate change poses a broad range of health risks, and the synergistic effects of extreme temperature co-occurring with other hazardous exposures such as air pollution may result in higher risks of all-cause mortality and cardiovascular and respiratory morbidity than exposure to either event alone. There are a number of hypothesized mechanisms for this interaction effect, including increased susceptibility to heat effects on chronic conditions affected by air pollution exposure, exacerbation of pollution effects due to temperature-induced stress, and shared pathophysiological pathways (e.g., systemic inflammation), but specific physiological mechanisms are not well understood. In this editorial, the authors discuss this aspect of a recently published study examining ambient formaldehyde combined with high temperature exposure and respiratory disease admissions among children. Here, the observation that the health effects of pollutants such as formaldehyde are amplified following periods of high temperature can help inform risk warning systems even without knowledge of the underlying physiological mechanisms, but a deeper biological understanding of the interaction effects of heat and ambient air pollution may better inform interventions. This is even more important in view of increases in both extreme temperature and pollution events tied to climate change.

Chambliss, Sarah [University of Texas at Austin, T↗

Seasonal Host Shifts for Legionella Within an Industrial Water‐Cooling System

Legionella is a genus of environmental bacteria containing pathogenic species such as Legionella pneumophila that are responsible for Legionnaires' disease, a potentially fatal respiratory infection. Disease aetiology can involve Legionella replication intracellularly within protists and this study aimed to characterise the Legionella -protist relationship to develop novel outbreak prevention targets. Water and sediment samples were collected from a water-cooling tower in South Carolina over a 6-month period. Concomitantly, multiple environmental parameters were recorded. Bacterial and eukaryotic communities were characterised using 16S rRNA gene V4 region and a 252 bp fragment of 18S rRNA gene, respectively. Co-occurrence network analyses were performed to elucidate Legionella -protist correlations through time. We found that Legionella correlated with different protists as the seasons progressed. Acanthamoeba correlated with Legionella in early spring followed by Vannella and Korotnevella in late spring and early summer, and were joined by Echinamoeba in mid-summer. Vannella and Acanthamoeba are known potential hosts for Legionella , while Korotnevella is a potential undocumented host. Of the environmental parameters, temperature showed strong correlation with protists genera, suggesting that Legionella abundance was driven by temperature-dependent protist availability. Our results highlight ecological shifts that are associated with elevated Legionella levels, which offers potential targets to help predict and prevent disease outbreaks.

microbial communities↗