Study on the association between ambient air pollution and daily cardiovascular and respiratory mortality in an urban district of Beijing.

PubMed

Zhang, Fengying; Li, Liping; Krafft, Thomas; Lv, Jinmei; Wang, Wuyi; Pei, Desheng

2011-06-01

The association between daily cardiovascular/respiratory mortality and air pollution in an urban district of Beijing was investigated over a 6-year period (January 2003 to December 2008). The purpose of this study was to evaluate the relative importance of the major air pollutants [particulate matter (PM), SO2, NO2] as predictors of daily cardiovascular/respiratory mortality. The time-series studied comprises years with lower level interventions to control air pollution (2003-2006) and years with high level interventions in preparation for and during the Olympics/Paralympics (2007-2008). Concentrations of PM10, SO2, and NO2, were measured daily during the study period. A generalized additive model was used to evaluate daily numbers of cardiovascular/respiratory deaths in relation to each air pollutant, controlling for time trends and meteorological influences such as temperature and relative humidity. The results show that the daily cardiovascular/respiratory death rates were significantly associated with the concentration air pollutants, especially deaths related to cardiovascular disease. The current day effects of PM10 and NO2 were higher than that of single lags (distributed lags) and moving average lags for respiratory disease mortality. The largest RR of SO2 for respiratory disease mortality was in Lag02. For cardiovascular disease mortality, the largest RR was in Lag01 for PM10, and in current day (Lag0) for SO2 and NO2. NO2 was associated with the largest RRs for deaths from both cardiovascular disease and respiratory disease.

Override of spontaneous respiratory pattern generator reduces cardiovascular parasympathetic influence

NASA Technical Reports Server (NTRS)

Patwardhan, A. R.; Vallurupalli, S.; Evans, J. M.; Bruce, E. N.; Knapp, C. F.

1995-01-01

We investigated the effects of voluntary control of breathing on autonomic function in cardiovascular regulation. Variability in heart rate was compared between 5 min of spontaneous and controlled breathing. During controlled breathing, for 5 min, subjects voluntarily reproduced their own spontaneous breathing pattern (both rate and volume on a breath-by-breath basis). With the use of this experimental design, we could unmask the effects of voluntary override of the spontaneous respiratory pattern generator on autonomic function in cardiovascular regulation without the confounding effects of altered respiratory pattern. Results from 10 subjects showed that during voluntary control of breathing, mean values of heart rate and blood pressure increased, whereas fractal and spectral powers in heart rate in the respiratory frequency region decreased. End-tidal PCO2 was similar during spontaneous and controlled breathing. These results indicate that the act of voluntary control of breathing decreases the influence of the vagal component, which is the principal parasympathetic influence in cardiovascular regulation.

Air pollution and cardiovascular and respiratory emergency visits in Central Arkansas: A time-series analysis.

PubMed

Rodopoulou, Sophia; Samoli, Evangelia; Chalbot, Marie-Cecile G; Kavouras, Ilias G

2015-12-01

Heart disease and stroke mortality and morbidity rates in Arkansas are among the highest in the U.S. While the effect of air pollution on cardiovascular health was identified in traffic-dominated metropolitan areas, there is a lack of studies for populations with variable exposure profiles, demographic and disease characteristics. Determine the short-term effects of air pollution on cardiovascular and respiratory morbidity in the stroke and heart failure belt. We investigated the associations of fine particles and ozone with respiratory and cardiovascular emergency room visits during the 2002-2012 period for adults in Central Arkansas using Poisson generalized models adjusted for temporal, seasonal and meteorological effects. We evaluated sensitivity of the associations to mutual pollutant adjustment and effect modification patterns by sex, age, race and season. We found effects on cardiovascular and respiratory emergencies for PM2.5 (1.52% [95% (confidence interval) CI: -1.10%, 4.20%]; 1.45% [95%CI: -2.64%, 5.72%] per 10 μg/m3) and O3 (0.93% [95%CI: -0.87%, 2.76%]; 0.76 [95%CI: -1.92%, 3.52%] per 10 ppbv) during the cold period (October-March). The effects were stronger among whites, except for the respiratory effects of O3 that were higher among Blacks/African-Americans. Effect modification patterns by age and sex differed by association. Both pollutants were associated with increases in emergency room visits for hypertension, heart failure and asthma. Effects on cardiovascular and respiratory emergencies were observed during the cold period when particulate matter was dominated by secondary nitrate and wood burning. Outdoor particulate pollution during winter had an effect on cardiovascular morbidity in central Arkansas, the region with high stroke and heart disease incidence rates. Copyright © 2015 Elsevier B.V. All rights reserved.

Risk assessment for cardiovascular and respiratory mortality due to air pollution and synoptic meteorology in 10 Canadian cities.

PubMed

Vanos, Jennifer K; Hebbern, Christopher; Cakmak, Sabit

2014-02-01

Synoptic weather and ambient air quality synergistically influence human health. We report the relative risk of mortality from all non-accidental, respiratory-, and cardiovascular-related causes, associated with exposure to four air pollutants, by weather type and season, in 10 major Canadian cities for 1981 through 1999. We conducted this multi-city time-series study using Poisson generalized linear models stratified by season and each of six distinctive synoptic weather types. Statistically significant relationships of mortality due to short-term exposure to carbon monoxide, nitrogen dioxide, sulphur dioxide, and ozone were found, with significant modifications of risk by weather type, season, and mortality cause. In total, 61% of the respiratory-related mortality relative risk estimates were significantly higher than for cardiovascular-related mortality. The combined effect of weather and air pollution is greatest when tropical-type weather is present in the spring or summer. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Mathematical modeling of human cardiovascular system for simulation of orthostatic response

NASA Technical Reports Server (NTRS)

Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.

1992-01-01

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

Does respiratory health contribute to the effects of long-term air pollution exposure on cardiovascular mortality?

PubMed

Schikowski, Tamara; Sugiri, Dorothea; Ranft, Ulrich; Gehring, Ulrike; Heinrich, Joachim; Wichmann, H-Erich; Krämer, Ursula

2007-03-07

There is growing epidemiological evidence that short-term and long-term exposure to high levels of air pollution may increase cardiovascular morbidity and mortality. In addition, epidemiological studies have shown an association between air pollution exposure and respiratory health. To what extent the association between cardiovascular mortality and air pollution is driven by the impact of air pollution on respiratory health is unknown. The aim of this study was to investigate whether respiratory health at baseline contributes to the effects of long-term exposure to high levels of air pollution on cardiovascular mortality in a cohort of elderly women. We analyzed data from 4750 women, aged 55 at the baseline investigation in the years 1985-1994. 2593 of these women had their lung function tested by spirometry. Respiratory diseases and symptoms were asked by questionnaire. Ambient air pollution exposure was assessed by the concentrations of NO2 and total suspended particles at fixed monitoring sites and by the distance of residency to a major road. A mortality follow-up of these women was conducted between 2001 and 2003. For the statistical analysis, Cox' regression was used. Women with impaired lung function or pre-existing respiratory diseases had a higher risk of dying from cardiovascular causes. The impact of impaired lung function declined over time. The risk ratio (RR) of women with forced expiratory volume in one second (FEV1) of less than 80% predicted to die from cardiovascular causes was RR = 3.79 (95%CI: 1.64-8.74) at 5 years survival time and RR = 1.35 (95%CI: 0.66-2.77) at 12 years. The association between air pollution levels and cardiovascular death rate was strong and statistically significant. However, this association did only change marginally when including indicators of respiratory health into the regression analysis. Furthermore, no interaction between air pollution and respiratory health on cardiovascular mortality indicating a higher risk of

Respiratory and cardiovascular effects of metals in ambient particulate matter: a critical review.

PubMed

Gray, Deborah L; Wallace, Lance A; Brinkman, Marielle C; Buehler, Stephanie S; La Londe, Chris

2015-01-01

In this review, we critically evaluated the epidemiological and toxicological evidence for the role of specific transition metals (As. Cr. Cu. Fe. Mn. Ni. Sc. Ti. V and Zn) in causing or contributing to the respiratory and cardiovascular health effects associated with ambient PM. Although the epidemiologic studies arc suggestive. and both the in vivo and in vitro laboratory studies document the toxicity of specific metals (Fe. Ni. V and Zn). the overall weight of evidence does not convincingly implicate metals as major contributors to health effects. None of the epidemiology studies that we reviewed conclusively implicated specific transition metals as having caused the respiratory and cardiovascular effects associated with ambient levels of PM. However, the studies reviewed tended to be internal ly consistent in identifying some metals (Fe, Ni, V and Zn) more frequently than others (As, Cu, Mn and Sc) as having positive associations wi th health effects. The major problem wi th which the epidemiological studies were faced was classifying and quantifying exposure. Community and population exposures to metals or other components of ambient PM were inferred from centrally- located samplers that may not accurately represent individual level exposures. Only a few authors reported findings that did not support the stated premise of the study; indeed, statistic ally significant associations are not necessarily biologically significant. It is likely that ·'negative studies" are under-represented in the published literature, making it a challenge to achieve a balanced evaluation of the role of metals in causing health effects associated with ambient PM. Both the in vivo and in vitro study results demonstrated that individual metals (Cu. Fe. Ni. V and Zn) and extracts of metals from ambient PM sources can produce acute inflammatory responses. However. the doses administered to laboratory animals were many orders of magnitude greater than what humans experience from

Association between daily mortality from respiratory and cardiovascular diseases and air pollution in Taiwan.

PubMed

Liang, Wen-Miin; Wei, Hsing-Yu; Kuo, Hsien-Wen

2009-01-01

Many studies have investigated the effects of air pollutants on disease and mortality. However, the results remain inconsistent and inconclusive. We thought that the impact of different seasons or ages of people may explain these differences. Measurement of the five pollutants (particulate matter <10 microm in aerodynamic diameter (PM(10)), SO(2), NO(2), O(3), and CO) was monitored by automated measuring units at five different stations. Monitoring stations were provided by the Taiwan Environmental Protection Agency (EPA) from 1997 to 1999. The subjects in the study were classified in two groups: those 65 years of age and older, and those of all ages (including the subjects in the > or =65 group). Data on daily mortality caused by respiratory disease, cardiovascular disease, and all other causes including the two aforementioned was collected by the Taiwan Department of Health (DOH). A time-series regression model was used to analyze the relative risk of respiratory and cardiovascular diseases due to air pollution in the summer and winter seasons. Risk of death from all causes and mortality from cardiovascular diseases during winter was significantly positively correlated with levels of SO(2), CO, and NO(2) for both groups of subjects and additionally with PM(10) for the elderly (> or =65 years old) group. There were significant positive correlations with respiratory diseases and levels of O(3) for both groups. However, the only significant positive correlation was with O(3) (RR=1.283) for the elderly group during summer. No other parameters showed significance for either group. Our findings contribute to the evidence of an association between SO(2), CO, NO(2), and PM(10) and mortality from respiratory and cardiovascular diseases, especially among elderly people during the winter season.

Summer indoor heat exposure and respiratory and cardiovascular distress calls in New York City, NY, U.S

PubMed Central

Uejio, C. K.; Tamerius, J. D.; Vredenburg, J.; Asaeda, G.; Isaacs, D. A.; Braun, J.; Quinn, A.; Freese, J. P.

2016-01-01

Most extreme heat studies relate outdoor weather conditions to human morbidity and mortality. In developed nations, individuals spend ~90% of their time indoors. This pilot study investigated the indoor environments of people receiving emergency medical care in New York City, NY, U.S., from July to August 2013. The first objective was to determine the relative influence of outdoor conditions as well as patient characteristics and neighborhood sociodemographics on indoor temperature and specific humidity (N = 764). The second objective was to determine whether cardiovascular or respiratory cases experience hotter and more humid indoor conditions as compared to controls. Paramedics carried portable sensors into buildings where patients received care to passively monitor indoor temperature and humidity. The case–control study compared 338 respiratory cases, 291 cardiovascular cases, and 471 controls. Intuitively, warmer and sunnier outdoor conditions increased indoor temperatures. Older patients who received emergency care tended to occupy warmer buildings. Indoor-specific humidity levels quickly adjusted to outdoor conditions. Indoor heat and humidity exposure above a 26 °C threshold increased (OR: 1.63, 95% CI: 0.98–2.68, P = 0.056), but not significantly, the proportion of respiratory cases. Indoor heat exposures were similar between cardiovascular cases and controls. PMID:26086869

Traffic aerosol lobar doses deposited in the human respiratory system.

PubMed

Manigrasso, Maurizio; Vernale, Claudio; Avino, Pasquale

2017-06-01

Aerosol pollution in urban environments has been recognized to be responsible for important pathologies of the cardiovascular and respiratory systems. In this perspective, great attention has been addressed to Ultra Fine Particles (UFPs < 100 nm), because they efficiently penetrate into the respiratory system and are capable of translocating from the airways into the blood circulation. This paper describes the aerosol regional doses deposited in the human respiratory system in a high-traffic urban area. The aerosol measurements were carried out on a curbside in downtown Rome, on a street characterized by a high density of autovehicular traffic. Aerosol number-size distributions were measured by means of a Fast Mobility Particle Sizer in the range from 5.6 to 560 nm with a 1 s time resolution. Dosimetry estimates were performed with the Multiple-Path Particle Dosimetry model by means of the stochastic lung model. The exposure scenario close to traffic is represented by a sequence of short-term peak exposures: about 6.6 × 10 10 particles are deposited hourly into the respiratory system. After 1 h of exposure in proximity of traffic, 1.29 × 10 10 , 1.88 × 10 10 , and 3.45 × 10 10 particles are deposited in the head, tracheobronchial, and alveolar regions. More than 95 % of such doses are represented by UFPs. Finally, according to the greater dose estimated, the right lung lobes are expected to be more susceptible to respiratory pathologies than the left lobes.

Assessment of cardio-respiratory interactions in preterm infants by bivariate autoregressive modeling and surrogate data analysis.

PubMed

Indic, Premananda; Bloch-Salisbury, Elisabeth; Bednarek, Frank; Brown, Emery N; Paydarfar, David; Barbieri, Riccardo

2011-07-01

Cardio-respiratory interactions are weak at the earliest stages of human development, suggesting that assessment of their presence and integrity may be an important indicator of development in infants. Despite the valuable research devoted to infant development, there is still a need for specifically targeted standards and methods to assess cardiopulmonary functions in the early stages of life. We present a new methodological framework for the analysis of cardiovascular variables in preterm infants. Our approach is based on a set of mathematical tools that have been successful in quantifying important cardiovascular control mechanisms in adult humans, here specifically adapted to reflect the physiology of the developing cardiovascular system. We applied our methodology in a study of cardio-respiratory responses for 11 preterm infants. We quantified cardio-respiratory interactions using specifically tailored multivariate autoregressive analysis and calculated the coherence as well as gain using causal approaches. The significance of the interactions in each subject was determined by surrogate data analysis. The method was tested in control conditions as well as in two different experimental conditions; with and without use of mild mechanosensory intervention. Our multivariate analysis revealed a significantly higher coherence, as confirmed by surrogate data analysis, in the frequency range associated with eupneic breathing compared to the other ranges. Our analysis validates the models behind our new approaches, and our results confirm the presence of cardio-respiratory coupling in early stages of development, particularly during periods of mild mechanosensory intervention, thus encouraging further application of our approach. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

76 FR 62164 - VASRD Improvement Forum-Updating Disability Criteria for the Respiratory System, Cardiovascular...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... Respiratory System, Cardiovascular System, Hearing Impairment, and Ear, Nose and Throat Diseases AGENCY... System, Cardiovascular System, Hearing Impairment, and Ear, Nose and Throat Diseases. The purpose of this...) the Cardiovascular System (38 CFR 4.100-4.104), (3) the Impairment of Auditory Acuity (38 CFR 4.85 and...

Exploring the Halal Status of Cardiovascular, Endocrine, and Respiratory Group of Medications

PubMed Central

Sarriff, Azmi; Abdul razzaq, Hadeer Akram

2013-01-01

Muslim consumers have special needs in medical treatment that differ from non-Muslim consumers. In particular, there is a growing demand among Muslim consumers for Halal medications. This descriptive exploratory study aims to determine the Halal status of selected cardiovascular, endocrine, and respiratory medications stored in an out-patient pharmacy in a Malaysian governmental hospital. Sources of active ingredients and excipients for each product were assessed for Halal status based on available information obtained from product leaflets, the Medical Information Management System (MIMS) website, or manufacturers. Halal status was based on the products’ sources and categorized into Halal, Mushbooh, or Haram. The proportions of Halal, Mushbooh, and Haram products were at 19.1%, 57.1%, and 23.8%, respectively. The percentage of active ingredients for cardiovascular/endocrine products that were assessed as Haram was 5.3%; for respiratory medications, it was only 1.1%. For excipients, 1.7% and 4.8% fall under the category of Haram for cardiovascular/endocrine products and respiratory products, respectively. Ethanol and magnesium stearate were found to be the common substances that were categorized as Haram and Mushbooh. PMID:23785257

Mathematical modelling of the human cardiovascular system in the presence of stenosis

NASA Technical Reports Server (NTRS)

Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

1993-01-01

This paper reports a theoretical study on the distribution of blood flow in the human cardiovascular system when one or more blood vessels are affected by stenosis. The analysis employs a mathematical model of the entire system based on the finite element method. The arterial-venous network is represented by a large number of interconnected segments in the model. Values for the model parameters are based upon the published data on the physiological and rheological properties of blood. Computational results show how blood flow through various parts of the cardiovascular system is affected by stenosis in different blood vessels. No significant changes in the flow parameters of the cardiovascular system were found to occur when the reduction in the lumen diameter of the stenosed vessels was less than 65%.

Cardiovascular Outcomes after a Respiratory Tract Infection among Adults with Non-Cystic Fibrosis Bronchiectasis: A General Population-based Study.

PubMed

Navaratnam, Vidya; Root, Adrian A; Douglas, Ian; Smeeth, Liam; Hubbard, Richard B; Quint, Jennifer K

2018-03-01

Studies suggest that adults with bronchiectasis are at increased risk of cardiovascular comorbidities. We aimed to quantify the relative risk of incident cardiovascular events after a respiratory tract infection among adults with bronchiectasis. Using UK electronic primary care records, we conducted a within-person comparison using the self-controlled case series method. We calculated the relative risk of first-time cardiovascular events (either first myocardial infarction or stroke) after a respiratory tract infection compared with the individual's baseline risk. Our cohort consisted of 895 adult men and women with non-cystic fibrosis bronchiectasis with a first myocardial infarction or stroke and at least one respiratory tract infection. There was an increased rate of first-time cardiovascular events in the 91-day period after a respiratory tract infection (incidence rate ratio, 1.56; 95% confidence interval, 1.20-2.02). The rate of a first cardiovascular event was highest in the first 3 days after a respiratory tract infection (incidence rate ratio, 2.73; 95% confidence interval, 1.41-5.27). These data suggest that respiratory tract infections are strongly associated with a transient increased risk of first-time myocardial infarction or stroke among people with bronchiectasis. As respiratory tract infections are six times more common in people with bronchiectasis than the general population, the increased risk has a disproportionately greater impact in these individuals. These findings may have implications for including cardiovascular risk modifications in airway infection treatment pathways in this population.

Associations of short-term exposure to traffic-related air pollution with cardiovascular and respiratory hospital admissions in London, UK

PubMed Central

Samoli, Evangelia; Atkinson, Richard W; Analitis, Antonis; Fuller, Gary W; Green, David C; Mudway, Ian; Anderson, H Ross; Kelly, Frank J

2016-01-01

Objectives There is evidence of adverse associations between short-term exposure to traffic-related pollution and health, but little is known about the relative contribution of the various sources and particulate constituents. Methods For each day for 2011–2012 in London, UK over 100 air pollutant metrics were assembled using monitors, modelling and chemical analyses. We selected a priori metrics indicative of traffic sources: general traffic, petrol exhaust, diesel exhaust and non-exhaust (mineral dust, brake and tyre wear). Using Poisson regression models, controlling for time-varying confounders, we derived effect estimates for cardiovascular and respiratory hospital admissions at prespecified lags and evaluated the sensitivity of estimates to multipollutant modelling and effect modification by season. Results For single day exposure, we found consistent associations between adult (15–64 years) cardiovascular and paediatric (0–14 years) respiratory admissions with elemental and black carbon (EC/BC), ranging from 0.56% to 1.65% increase per IQR change, and to a lesser degree with carbon monoxide (CO) and aluminium (Al). The average of past 7 days EC/BC exposure was associated with elderly (65+ years) cardiovascular admissions. Indicated associations were higher during the warm period of the year. Although effect estimates were sensitive to the adjustment for other pollutants they remained consistent in direction, indicating independence of associations from different sources, especially between diesel and petrol engines, as well as mineral dust. Conclusions Our results suggest that exhaust related pollutants are associated with increased numbers of adult cardiovascular and paediatric respiratory hospitalisations. More extensive monitoring in urban centres is required to further elucidate the associations. PMID:26884048

Effects of bedrest 1: cardiovascular, respiratory and haematological systems.

PubMed

Knight, John; Nigam, Yamni; Jones, Aled

This is the first in a three-part series on the physiological effects of bedrest. It discusses what happens to the cardiovascular, respiratory and haematological systems when a person is bedridden. Other articles in the series will cover the effects of immobility on the digestive, endocrine, renal, nervous, immune and musculoskeletal systems and will examine the effects of bedrest on the skin.

Equation Discovery for Model Identification in Respiratory Mechanics of the Mechanically Ventilated Human Lung

NASA Astrophysics Data System (ADS)

Ganzert, Steven; Guttmann, Josef; Steinmann, Daniel; Kramer, Stefan

Lung protective ventilation strategies reduce the risk of ventilator associated lung injury. To develop such strategies, knowledge about mechanical properties of the mechanically ventilated human lung is essential. This study was designed to develop an equation discovery system to identify mathematical models of the respiratory system in time-series data obtained from mechanically ventilated patients. Two techniques were combined: (i) the usage of declarative bias to reduce search space complexity and inherently providing the processing of background knowledge. (ii) A newly developed heuristic for traversing the hypothesis space with a greedy, randomized strategy analogical to the GSAT algorithm. In 96.8% of all runs the applied equation discovery system was capable to detect the well-established equation of motion model of the respiratory system in the provided data. We see the potential of this semi-automatic approach to detect more complex mathematical descriptions of the respiratory system from respiratory data.

Hospital admissions in Iran for cardiovascular and respiratory diseases attributed to the Middle Eastern Dust storms.

PubMed

Khaniabadi, Yuef Omidi; Fanelli, Roberto; De Marco, Alessandra; Daryanoosh, Seyed Mohammad; Kloog, Itai; Hopke, Philip K; Conti, Gea Oliveri; Ferrante, Margherita; Mohammadi, Mohammad Javad; Babaei, Ali Akbar; Basiri, Hassan; Goudarzi, Gholamreza

2017-07-01

The main objective of this study was to assess the possible effects of airborne particulate matter less than 10 μm in diameter (PM 10 ) from the Middle Eastern Dust (MED) events on human health in Khorramabad (Iran) in terms of estimated hospital admissions (morbidity) for cardiovascular diseases (HACD) and for respiratory diseases (HARD) during the period of 2015 to 2016. The AirQ program developed by the World Health Organization (WHO) was used to estimate the potential health impacts to daily PM 10 exposures. The numbers of excess cases for cardiovascular/respiratory morbidity were 20/51, 72/185, and 20/53 on normal, dusty, and MED event days, respectively. The highest number of hospital admissions was estimated for PM 10 concentrations in the range of 40 to 49 μg/m 3 , i.e, lower than the daily (50 μg/m 3 ) limit value established by WHO. The results also showed that 4.7% (95% CI 3.2-6.7%) and 4.2% (95% CI 2.6-5.8%) of HARD and HACD, respectively, were attributed to PM 10 concentrations above 10 μg/m 3 . The study demonstrates a significant impact of air pollution on people, which is manifested primarily as respiratory and cardiovascular problems. To reduce these effects, several immediate actions should be taken by the local authorities to control the impacts of dust storms on residents' health, e.g., developing a green beltway along the Iran-Iraq border and management of water such as irrigation of dry areas that would be effective as mitigation strategies.

Air pollution and hospital admissions for respiratory and cardiovascular diseases in Hong Kong

PubMed Central

Wong, T. W.; Lau, T. S.; Yu, T. S.; Neller, A.; Wong, S. L.; Tam, W.; Pang, S. W.

1999-01-01

OBJECTIVE: To investigate short term effects of concentrations of pollutants in ambient air on hospital admissions for cardiovascular and respiratory diseases in Hong Kong. METHODS: Retrospective ecological study. A Poisson regression was performed of concentrations of daily air pollutant on daily counts of emergency hospital admissions in 12 major hospitals. The effects of time trend, season, and other cyclical factors, temperature, and humidity were accounted for. Autocorrelation and overdispersion were corrected. Daily concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3), and particulate matter < 10 microns in aerodynamic diameter (PM10) were obtained from seven air monitoring stations in Hong Kong in 1994 and 1995. Relative risks (RR) of respiratory and cardiovascular disease admissions (for an increase of 10 micrograms/m3 in concentration of air pollutant) were calculated. RESULTS: Significant associations were found between hospital admissions for all respiratory diseases, all cardiovascular diseases, chronic obstructive pulmonary diseases, and heart failure and the concentrations of all four pollutants. Admissions for asthma, pneumonia, and influenza were significantly associated with NO2, O3, and PM10. Relative risk (RR) for admissions for respiratory disease for the four pollutants ranged from 1.013 (for SO2) to 1.022 (for O3), and for admissions for cardiovascular disease, from 1.006 (for PM10) to 1.016 (for SO2). Those aged > or = 65 years were at higher risk. Significant positive interactions were detected between NO2, O3, and PM10, and between O3 and winter months. CONCLUSIONS: Adverse health effects are evident at current ambient concentrations of air pollutants. Further reduction in air pollution is necessary to protect the health of the community, especially that of the high risk group.   PMID:10658547

Cardiovascular and respiratory mortality attributed to ground-level ozone in Ahvaz, Iran.

PubMed

Goudarzi, Gholamreza; Geravandi, Sahar; Foruozandeh, Hossein; Babaei, Ali Akbar; Alavi, Nadali; Niri, Mehdi Vosoughi; Khodayar, Mohammad Javad; Salmanzadeh, Shokrollah; Mohammadi, Mohammad Javad

2015-08-01

Ahvaz, the capital city of Khuzestan Province, which produces Iran's most oil, is on the rolls of fame in view of air pollution. It has also suffered from dust storm during the recent two decades. So, emissions from transportation systems, steel, oil, black carbon, and other industries as anthropogenic sources and dust storm as a new phenomenon are two major concerns of air pollution in Ahvaz. Without any doubt, they can cause many serious problems for the environment and humans in this megacity. The main objective of the present study was to estimate the impact of ground-level ozone (GLO) as a secondary pollutant on human heath. Data of GLO in four monitoring stations were collected at the first step and they were processed and at the final step they were inserted to a health effect model. Findings showed that cumulative cases of cardiovascular and respiratory deaths which attributed to GLO were 43 and 173 persons, respectively. Corresponding RR for these two events were 1.008 (95% CI) and 1.004 (95% CI), respectively. Although we did not provide a distinction between winter and summer in case of mentioned mortalities attributed to GLO, ozone concentrations in winter due to more fuel consumption and sub adiabatic condition in tropospheric atmospherewere higher than those GLO in summer.

Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

NASA Technical Reports Server (NTRS)

Cohen, Richard

1999-01-01

Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether

Risk of respiratory and cardiovascular hospitalisation with exposure to bushfire particulates: new evidence from Darwin, Australia.

PubMed

Crabbe, Helen

2012-12-01

The risk of hospitalisation from bushfire exposure events in Darwin, Australia, is examined. Several local studies have found evidence for the effects of exposure to bushfire particulates on respiratory and cardiovascular hospital admissions. They have characterised the risk of admission from seasonal exposures to biomass air pollution. A new, unanalysed data set presented an additional chance to examine unique exposure effects, as there are no anthropogenic sources of particulates in the vicinity of the exposure monitor. The incidence of daily counts of hospital admissions for respiratory and cardiovascular diagnoses was calculated with respect to exposures of particulate matter (PM(10)), course particulate matter, fine particulate matter (FPM) and black carbon composition. A Poisson model was used to calculate unadjusted (crude) measures of effect and then adjusted for known risk factors and confounders. The final model adjusted for the effects of minimum temperature, relative humidity, a smoothed spline for seasonal effects, 'date' for a linear effect over time, day of the week and public and school holidays. A subset analysis adjusted for an influenza epidemic in a particular year. The main findings suggest that respiratory admissions were associated with exposure to PM(10) with a lag of 1 day when adjusted for flu and other confounders (RR = 1.025, 95 % CI 1.000-1.051, p < 0.05). This effect is strongest for exposure to FPM concentrations (RR = 1.091, 95 % CI 1.023-1.163, p < 0.01) when adjusted for flu. Respiratory admissions were also associated with black carbon concentrations recorded the previous day (RR = 1.0004, 95 % CI 1.000-1.0008, p < 0.05), which did not change strength when adjusted for flu. Cardiovascular admissions had the strongest association with exposure to same-day PM and highest RR for exposure to FPM when adjusted for confounders (RR = 1.044, 95 % CI 0.989-1.102). Consistent risks were also found with exposure to black carbon with lags of

Associations of short-term exposure to traffic-related air pollution with cardiovascular and respiratory hospital admissions in London, UK.

PubMed

Samoli, Evangelia; Atkinson, Richard W; Analitis, Antonis; Fuller, Gary W; Green, David C; Mudway, Ian; Anderson, H Ross; Kelly, Frank J

2016-05-01

There is evidence of adverse associations between short-term exposure to traffic-related pollution and health, but little is known about the relative contribution of the various sources and particulate constituents. For each day for 2011-2012 in London, UK over 100 air pollutant metrics were assembled using monitors, modelling and chemical analyses. We selected a priori metrics indicative of traffic sources: general traffic, petrol exhaust, diesel exhaust and non-exhaust (mineral dust, brake and tyre wear). Using Poisson regression models, controlling for time-varying confounders, we derived effect estimates for cardiovascular and respiratory hospital admissions at prespecified lags and evaluated the sensitivity of estimates to multipollutant modelling and effect modification by season. For single day exposure, we found consistent associations between adult (15-64 years) cardiovascular and paediatric (0-14 years) respiratory admissions with elemental and black carbon (EC/BC), ranging from 0.56% to 1.65% increase per IQR change, and to a lesser degree with carbon monoxide (CO) and aluminium (Al). The average of past 7 days EC/BC exposure was associated with elderly (65+ years) cardiovascular admissions. Indicated associations were higher during the warm period of the year. Although effect estimates were sensitive to the adjustment for other pollutants they remained consistent in direction, indicating independence of associations from different sources, especially between diesel and petrol engines, as well as mineral dust. Our results suggest that exhaust related pollutants are associated with increased numbers of adult cardiovascular and paediatric respiratory hospitalisations. More extensive monitoring in urban centres is required to further elucidate the associations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Biophysical Model of Ion Transport across Human Respiratory Epithelia Allows Quantification of Ion Permeabilities

PubMed Central

Garcia, Guilherme J.M.; Boucher, Richard C.; Elston, Timothy C.

2013-01-01

Lung health and normal mucus clearance depend on adequate hydration of airway surfaces. Because transepithelial osmotic gradients drive water flows, sufficient hydration of the airway surface liquid depends on a balance between ion secretion and absorption by respiratory epithelia. In vitro experiments using cultures of primary human nasal epithelia and human bronchial epithelia have established many of the biophysical processes involved in airway surface liquid homeostasis. Most experimental studies, however, have focused on the apical membrane, despite the fact that ion transport across respiratory epithelia involves both cellular and paracellular pathways. In fact, the ion permeabilities of the basolateral membrane and paracellular pathway remain largely unknown. Here we use a biophysical model for water and ion transport to quantify ion permeabilities of all pathways (apical, basolateral, paracellular) in human nasal epithelia cultures using experimental (Ussing Chamber and microelectrode) data reported in the literature. We derive analytical formulas for the steady-state short-circuit current and membrane potential, which are for polarized epithelia the equivalent of the Goldman-Hodgkin-Katz equation for single isolated cells. These relations allow parameter estimation to be performed efficiently. By providing a method to quantify all the ion permeabilities of respiratory epithelia, the model may aid us in understanding the physiology that regulates normal airway surface hydration. PMID:23442922

Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

2010-01-01

Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

Incidence and Risk Factors for Perioperative Cardiovascular and Respiratory Adverse Events in Pediatric Patients With Congenital Heart Disease Undergoing Noncardiac Procedures.

PubMed

Lee, Sandra; Reddington, Elise; Koutsogiannaki, Sophia; Hernandez, Michael R; Odegard, Kirsten C; DiNardo, James A; Yuki, Koichi

2018-04-27

While mortality and adverse perioperative events after noncardiac surgery in children with a broad range of congenital cardiac lesions have been investigated using large multiinstitutional databases, to date single-center studies addressing adverse outcomes in children with congenital heart disease (CHD) undergoing noncardiac surgery have only included small numbers of patients with significant heart disease. The primary objective of this study was to determine the incidences of perioperative cardiovascular and respiratory events in a large cohort of patients from a single institution with a broad range of congenital cardiac lesions undergoing noncardiac procedures and to determine risk factors for these events. We identified 3010 CHD patients presenting for noncardiac procedures in our institution over a 5-year period. We collected demographic information, including procedure performed, cardiac diagnosis, ventricular function as assessed by echocardiogram within 6 months of the procedure, and classification of CHD into 3 groups (minor, major, or severe CHD) based on residual lesion burden and cardiovascular functional status. Characteristics related to conduct of anesthesia care were also collected. The primary outcome variables for our analysis were the incidences of intraoperative cardiovascular and respiratory events. Univariable and multivariable logistic regressions were used to determine risk factors for these 2 outcomes. The incidence of cardiovascular events was 11.5% and of respiratory events was 4.7%. Univariate analysis and multivariable analysis demonstrated that American Society of Anesthesiologists (≥3), emergency cases, major and severe CHD, single-ventricle physiology, ventricular dysfunction, orthopedic surgery, general surgery, neurosurgery, and pulmonary procedures were associated with perioperative cardiovascular events. Respiratory events were associated with American Society of Anesthesiologists (≥4) and otolaryngology, gastrointestinal

Assessment of the Possible Association of Air Pollutants PM10, O3, NO2 With an Increase in Cardiovascular, Respiratory, and Diabetes Mortality in Panama City

PubMed Central

Zúñiga, Julio; Tarajia, Musharaf; Herrera, Víctor; Urriola, Wilfredo; Gómez, Beatriz; Motta, Jorge

2016-01-01

Abstract In recent years, Panama has experienced a marked economic growth, and this, in turn, has been associated with rapid urban development and degradation of air quality. This study is the first evaluation done in Panama on the association between air pollution and mortality. Our objective was to assess the possible association between monthly levels of PM10, O3, and NO2, and cardiovascular, respiratory, and diabetes mortality, as well as the seasonal variation of mortality in Panama City, Panama. The study was conducted in Panama City, using air pollution data from January 2003 to December 2013. We utilized a Poisson regression model based on generalized linear models, to evaluate the association between PM10, NO2, and O3 exposure and mortality from diabetes, cardiovascular, and respiratory diseases. The sample size for PM10, NO2, and O2 was 132, 132, and 108 monthly averages, respectively. We found that levels of PM10, O3, and NO2 were associated with increases in cardiovascular, respiratory, and diabetes mortality. For PM10 levels ≥ 40 μg/m3, we found an increase in cardiovascular mortality of 9.7% (CI 5.8–13.6%), and an increase of 12.6% (CI 0.2–24.2%) in respiratory mortality. For O3 levels ≥ 20 μg/m3 we found an increase of 32.4% (IC 14.6–52.9) in respiratory mortality, after a 2-month lag period following exposure in the 65 to <74 year-old age group. For NO2 levels ≥20 μg/m3 we found an increase in respiratory mortality of 11.2% (IC 1.9–21.3), after a 2-month lag period following exposure among those aged between 65 and <74 years. There could be an association between the air pollution in Panama City and an increase in cardiovascular, respiratory, and diabetes mortality. This study confirms the urgent need to improve the measurement frequency of air pollutants in Panama. PMID:26765444

Biophysical model of ion transport across human respiratory epithelia allows quantification of ion permeabilities.

PubMed

Garcia, Guilherme J M; Boucher, Richard C; Elston, Timothy C

2013-02-05

Lung health and normal mucus clearance depend on adequate hydration of airway surfaces. Because transepithelial osmotic gradients drive water flows, sufficient hydration of the airway surface liquid depends on a balance between ion secretion and absorption by respiratory epithelia. In vitro experiments using cultures of primary human nasal epithelia and human bronchial epithelia have established many of the biophysical processes involved in airway surface liquid homeostasis. Most experimental studies, however, have focused on the apical membrane, despite the fact that ion transport across respiratory epithelia involves both cellular and paracellular pathways. In fact, the ion permeabilities of the basolateral membrane and paracellular pathway remain largely unknown. Here we use a biophysical model for water and ion transport to quantify ion permeabilities of all pathways (apical, basolateral, paracellular) in human nasal epithelia cultures using experimental (Ussing Chamber and microelectrode) data reported in the literature. We derive analytical formulas for the steady-state short-circuit current and membrane potential, which are for polarized epithelia the equivalent of the Goldman-Hodgkin-Katz equation for single isolated cells. These relations allow parameter estimation to be performed efficiently. By providing a method to quantify all the ion permeabilities of respiratory epithelia, the model may aid us in understanding the physiology that regulates normal airway surface hydration. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Evaluation of the educational value of YouTube videos about physical examination of the cardiovascular and respiratory systems.

PubMed

Azer, Samy A; Algrain, Hala A; AlKhelaif, Rana A; AlEshaiwi, Sarah M

2013-11-13

A number of studies have evaluated the educational contents of videos on YouTube. However, little analysis has been done on videos about physical examination. This study aimed to analyze YouTube videos about physical examination of the cardiovascular and respiratory systems. It was hypothesized that the educational standards of videos on YouTube would vary significantly. During the period from November 2, 2011 to December 2, 2011, YouTube was searched by three assessors for videos covering the clinical examination of the cardiovascular and respiratory systems. For each video, the following information was collected: title, authors, duration, number of viewers, and total number of days on YouTube. Using criteria comprising content, technical authority, and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-useful videos. A total of 1920 videos were screened. Only relevant videos covering the examination of adults in the English language were identified (n=56). Of these, 20 were found to be relevant to cardiovascular examinations and 36 to respiratory examinations. Further analysis revealed that 9 provided useful information on cardiovascular examinations and 7 on respiratory examinations: scoring mean 14.9 (SD 0.33) and mean 15.0 (SD 0.00), respectively. The other videos, 11 covering cardiovascular and 29 on respiratory examinations, were not useful educationally, scoring mean 11.1 (SD 1.08) and mean 11.2 (SD 1.29), respectively. The differences between these two categories were significant (P<.001 for both body systems). The concordance between the assessors on applying the criteria was 0.89, with a kappa score >.86. A small number of videos about physical examination of the cardiovascular and respiratory systems were identified as educationally useful; these videos can be used by medical students for independent learning and by clinical teachers as learning resources. The scoring system utilized by

Evaluation of the Educational Value of YouTube Videos About Physical Examination of the Cardiovascular and Respiratory Systems

PubMed Central

2013-01-01

Background A number of studies have evaluated the educational contents of videos on YouTube. However, little analysis has been done on videos about physical examination. Objective This study aimed to analyze YouTube videos about physical examination of the cardiovascular and respiratory systems. It was hypothesized that the educational standards of videos on YouTube would vary significantly. Methods During the period from November 2, 2011 to December 2, 2011, YouTube was searched by three assessors for videos covering the clinical examination of the cardiovascular and respiratory systems. For each video, the following information was collected: title, authors, duration, number of viewers, and total number of days on YouTube. Using criteria comprising content, technical authority, and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-useful videos. Results A total of 1920 videos were screened. Only relevant videos covering the examination of adults in the English language were identified (n=56). Of these, 20 were found to be relevant to cardiovascular examinations and 36 to respiratory examinations. Further analysis revealed that 9 provided useful information on cardiovascular examinations and 7 on respiratory examinations: scoring mean 14.9 (SD 0.33) and mean 15.0 (SD 0.00), respectively. The other videos, 11 covering cardiovascular and 29 on respiratory examinations, were not useful educationally, scoring mean 11.1 (SD 1.08) and mean 11.2 (SD 1.29), respectively. The differences between these two categories were significant (P<.001 for both body systems). The concordance between the assessors on applying the criteria was 0.89, with a kappa score >.86. Conclusions A small number of videos about physical examination of the cardiovascular and respiratory systems were identified as educationally useful; these videos can be used by medical students for independent learning and by clinical teachers as

A UWB Radar Signal Processing Platform for Real-Time Human Respiratory Feature Extraction Based on Four-Segment Linear Waveform Model.

PubMed

Hsieh, Chi-Hsuan; Chiu, Yu-Fang; Shen, Yi-Hsiang; Chu, Ta-Shun; Huang, Yuan-Hao

2016-02-01

This paper presents an ultra-wideband (UWB) impulse-radio radar signal processing platform used to analyze human respiratory features. Conventional radar systems used in human detection only analyze human respiration rates or the response of a target. However, additional respiratory signal information is available that has not been explored using radar detection. The authors previously proposed a modified raised cosine waveform (MRCW) respiration model and an iterative correlation search algorithm that could acquire additional respiratory features such as the inspiration and expiration speeds, respiration intensity, and respiration holding ratio. To realize real-time respiratory feature extraction by using the proposed UWB signal processing platform, this paper proposes a new four-segment linear waveform (FSLW) respiration model. This model offers a superior fit to the measured respiration signal compared with the MRCW model and decreases the computational complexity of feature extraction. In addition, an early-terminated iterative correlation search algorithm is presented, substantially decreasing the computational complexity and yielding negligible performance degradation. These extracted features can be considered the compressed signals used to decrease the amount of data storage required for use in long-term medical monitoring systems and can also be used in clinical diagnosis. The proposed respiratory feature extraction algorithm was designed and implemented using the proposed UWB radar signal processing platform including a radar front-end chip and an FPGA chip. The proposed radar system can detect human respiration rates at 0.1 to 1 Hz and facilitates the real-time analysis of the respiratory features of each respiration period.

The human respiratory gate

NASA Technical Reports Server (NTRS)

Eckberg, Dwain L.

2003-01-01

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.

Research Summary 3-D Computational Fluid Dynamics (CFD) Model Of The Human Respiratory System

EPA Science Inventory

The U.S. EPA’s Office of Research and Development (ORD) has developed a 3-D computational fluid dynamics (CFD) model of the human respiratory system that allows for the simulation of particulate based contaminant deposition and clearance, while being adaptable for age, ethnicity,...

Innovative model to simulate exhalation phase in human respiratory system.

PubMed

Sbrana, Tommaso; Landi, Alberto; Catapano, Giosuè Angelo

2011-11-01

In this paper, we present a mathematical model, which mimics the bronchial resistances of human's lung in an expiratory act. The model is implemented in Matlab. The inputs that are used in this model derive from spirometry test. This model is able to study a physiologic condition, a pathologic one and the patient's follow up after drug treatment. We split our study into two parts. The first one focuses the analysis on the gas fluido dynamic inside of the respiratory pathways. The second part takes care of the pressure equilibrium in the exchange zone. We use the outputs that derive from the second subsystem to solve the Bernoulli's equation of the first part. The model was validated with data provided from "Clinical Physiology Institute" of CNR and G. Monasterio Foundation of Pisa. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A concentrated parameter model for the human cardiovascular system including heart valve dynamics and atrioventricular interaction.

PubMed

Korakianitis, Theodosios; Shi, Yubing

2006-09-01

Numerical modeling of the human cardiovascular system has always been an active research direction since the 19th century. In the past, various simulation models of different complexities were proposed for different research purposes. In this paper, an improved numerical model to study the dynamic function of the human circulation system is proposed. In the development of the mathematical model, the heart chambers are described with a variable elastance model. The systemic and pulmonary loops are described based on the resistance-compliance-inertia concept by considering local effects of flow friction, elasticity of blood vessels and inertia of blood in different segments of the blood vessels. As an advancement from previous models, heart valve dynamics and atrioventricular interaction, including atrial contraction and motion of the annulus fibrosus, are specifically modeled. With these improvements the developed model can predict several important features that were missing in previous numerical models, including regurgitant flow on heart valve closure, the value of E/A velocity ratio in mitral flow, the motion of the annulus fibrosus (called the KG diaphragm pumping action), etc. These features have important clinical meaning and their changes are often related to cardiovascular diseases. Successful simulation of these features enhances the accuracy of simulations of cardiovascular dynamics, and helps in clinical studies of cardiac function.

Burn Pit Emissions Exposure and Respiratory and Cardiovascular Conditions Among Airborne Hazards and Open Burn Pit Registry Participants.

PubMed

Liu, Jason; Lezama, Nicholas; Gasper, Joseph; Kawata, Jennifer; Morley, Sybil; Helmer, Drew; Ciminera, Paul

2016-07-01

The aim of this study was to determine how burn pit emissions exposure is associated with the incidence of respiratory and cardiovascular conditions. We examined the associations between assumed geographic and self-reported burn pit emissions exposure and respiratory and cardiovascular outcomes in participants of the Airborne Hazards and Open Burn Pit Registry. We found significant dose-response associations for higher risk of self-reported emphysema, chronic bronchitis, or chronic obstructive pulmonary disease with increased days of deployment within 2 miles of selected burn pits (P-trend = 0.01) and self-reported burn pit smoke exposure (P-trend = 0.0005). We found associations between burn pit emissions exposure and higher incidence of post-deployment self-reported respiratory and cardiovascular conditions, but these findings should be interpreted with caution because the surrogate measurements of burn pit emissions exposure in this analysis may not reflect individual exposure levels.

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathingmore » conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.« less

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditionsmore » using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.« less

Development of a mathematical model of the human cardiovascular system: An educational perspective

NASA Astrophysics Data System (ADS)

Johnson, Bruce Allen

A mathematical model of the human cardiovascular system will be a useful educational tool in biological sciences and bioengineering classrooms. The goal of this project is to develop a mathematical model of the human cardiovascular system that responds appropriately to variations of significant physical variables. Model development is based on standard fluid statics and dynamics principles, pressure-volume characteristics of the cardiac cycle, and compliant behavior of blood vessels. Cardiac cycle phases provide the physical and logical model structure, and Boolean algebra links model sections. The model is implemented using VisSim, a highly intuitive and easily learned block diagram modeling software package. Comparisons of model predictions of key variables to published values suggest that the model reasonably approximates expected behavior of those variables. The model responds plausibly to variations of independent variables. Projected usefulness of the model as an educational tool is threefold: independent variables which determine heart function may be easily varied to observe cause and effect; the model is used in an interactive setting; and the relationship of governing equations to model behavior is readily viewable and intuitive. Future use of this model in classrooms may give a more reasonable indication of its value as an educational tool.* *This dissertation includes a CD that is multimedia (contains text and other applications that are not available in a printed format). The CD requires the following applications: CorelPhotoHouse, CorelWordPerfect, VisSinViewer (included on CD), Internet access.

Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

PubMed Central

Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

2016-01-01

Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts.

PubMed

Stittelaar, Koert J; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J B; Fraaij, Pieter L A; van Baalen, Carel A; van Kampen, Jeroen J A; van der Vries, Erhard; Osterhaus, Albert D M E; de Swart, Rik L

2016-06-14

Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (10⁵ TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

A comparative meta-analysis of maximal aerobic metabolism of vertebrates: implications for respiratory and cardiovascular limits to gas exchange.

PubMed

Hillman, Stanley S; Hancock, Thomas V; Hedrick, Michael S

2013-02-01

Maximal aerobic metabolic rates (MMR) in vertebrates are supported by increased conductive and diffusive fluxes of O(2) from the environment to the mitochondria necessitating concomitant increases in CO(2) efflux. A question that has received much attention has been which step, respiratory or cardiovascular, provides the principal rate limitation to gas flux at MMR? Limitation analyses have principally focused on O(2) fluxes, though the excess capacity of the lung for O(2) ventilation and diffusion remains unexplained except as a safety factor. Analyses of MMR normally rely upon allometry and temperature to define these factors, but cannot account for much of the variation and often have narrow phylogenetic breadth. The unique aspect of our comparative approach was to use an interclass meta-analysis to examine cardio-respiratory variables during the increase from resting metabolic rate to MMR among vertebrates from fish to mammals, independent of allometry and phylogeny. Common patterns at MMR indicate universal principles governing O(2) and CO(2) transport in vertebrate cardiovascular and respiratory systems, despite the varied modes of activities (swimming, running, flying), different cardio-respiratory architecture, and vastly different rates of metabolism (endothermy vs. ectothermy). Our meta-analysis supports previous studies indicating a cardiovascular limit to maximal O(2) transport and also implicates a respiratory system limit to maximal CO(2) efflux, especially in ectotherms. Thus, natural selection would operate on the respiratory system to enhance maximal CO(2) excretion and the cardiovascular system to enhance maximal O(2) uptake. This provides a possible evolutionary explanation for the conundrum of why the respiratory system appears functionally over-designed from an O(2) perspective, a unique insight from previous work focused solely on O(2) fluxes. The results suggest a common gas transport blueprint, or Bauplan, in the vertebrate clade.

Particle deposition in human respiratory system: deposition of concentrated hygroscopic aerosols.

PubMed

Varghese, Suresh K; Gangamma, S

2009-06-01

In the nearly saturated human respiratory tract, the presence of water-soluble substances in the inhaled aerosols can cause change in the size distribution of the particles. This consequently alters the lung deposition profiles of the inhaled airborne particles. Similarly, the presence of high concentration of hygroscopic aerosols also affects the water vapor and temperature profiles in the respiratory tract. A model is presented to analyze these effects in human respiratory system. The model solves simultaneously the heat and mass transfer equations to determine the size evolution of respirable particles and gas-phase properties within human respiratory tract. First, the model predictions for nonhygroscopic aerosols are compared with experimental results. The model results are compared with experimental results of sodium chloride particles. The model reproduces the major features of the experimental data. The water vapor profile is significantly modified only when a high concentration of particles is present. The model is used to study the effect of equilibrium assumptions on particle deposition. Simulations show that an infinite dilution solution assumption to calculate the saturation equilibrium over droplet could induce errors in estimating particle growth. This error is significant in the case of particles of size greater than 1 mum and at number concentrations higher than 10(5)/cm(3).

Phase synchronization of oscillations in cardiovascular and respiratory systems in humans

NASA Astrophysics Data System (ADS)

Tankanag, Arina V.; Grinevich, Andrey A.; Tikhonova, Irina V.; Chaplygina, Alina V.; Chemeris, Nikolay K.

2017-04-01

Phase synchronization between blood flow oscillations of left and right forearm skin sites, heart rate variability (HRV) and breath rate were studied from healthy volunteers at rest. The degree of synchronization between the phases of the analyzed signals was estimated from the value of the wavelet phase coherence. High medians of values of phase wavelet coherence function were obtained for the endothelial, neurogenic, myogenic and cardiac intervals. Significant phase synchronization were demonstrated between HRV and skin blood flow oscillations in both left and right forearms in a wide frequency range from 0.04 to 0.4 Hz. Six participants exhibited low phase synchronization (< 0.5) between the breath rate and HRV, while nine participants had high phase synchronization (> 0.5). This distribution was not affected by the sex or sympathovagal status of volunteers. Participants with low phase synchronization between breath rate and HRV featured low phase synchronization (< 0.5) between breath rate and blood flow oscillations in both forearms. Contrariwise, in subjects with high phase synchronization between respiratory rhythm and HRV both low and high phase synchronization between breath rate and blood flow oscillations in both forearms was observed. The results obtained allow us to suggest that the organism possesses a mechanism mediating the synchronization of blood flow oscillations in the skin microvasculature with all other periodical processes across the cardiovascular system, in particular, with HRV and breath rate over a wide frequency range.

Three Measures of Forest Fire Smoke Exposure and Their Associations with Respiratory and Cardiovascular Health Outcomes in a Population-Based Cohort

PubMed Central

Brauer, Michael; MacNab, Ying C.; Kennedy, Susan M.

2011-01-01

Background: During the summer of 2003 numerous fires burned in British Columbia, Canada. Objectives: We examined the associations between respiratory and cardiovascular physician visits and hospital admissions, and three measures of smoke exposure over a 92-day study period (1 July to 30 September 2003). Methods: A population-based cohort of 281,711 residents was identified from administrative data. Spatially specific daily exposure estimates were assigned to each subject based on total measurements of particulate matter (PM) ≤ 10 μm in aerodynamic diameter (PM10) from six regulatory tapered element oscillating microbalance (TEOM) air quality monitors, smoke-related PM10 from a CALPUFF dispersion model run for the study, and a SMOKE exposure metric for plumes visible in satellite images. Logistic regression with repeated measures was used to estimate associations with each outcome. Results: The mean (± SD) exposure based on TEOM-measured PM10 was 29 ± 31 μg/m3, with an interquartile range of 14–31 μg/m3. Correlations between the TEOM, smoke, and CALPUFF metrics were moderate (0.37–0.76). Odds ratios (ORs) for a 30-μg/m3 increase in TEOM-based PM10 were 1.05 [95% confidence interval (CI), 1.03–1.06] for all respiratory physician visits, 1.16 (95% CI, 1.09–1.23) for asthma-specific visits, and 1.15 (95% CI, 1.00–1.29) for respiratory hospital admissions. Associations with cardiovascular outcomes were largely null. Conclusions: Overall we found that increases in TEOM-measured PM10 were associated with increased odds of respiratory physician visits and hospital admissions, but not with cardiovascular health outcomes. Results indicating effects of fire smoke on respiratory outcomes are consistent with previous studies, as are the null results for cardiovascular outcomes. Some agreement between TEOM and the other metrics suggests that exposure assessment tools that are independent of air quality monitoring may be useful with further refinement. PMID

Heat-related mortality projections for cardiovascular and respiratory disease under the changing climate in Beijing, China.

PubMed

Li, Tiantian; Ban, Jie; Horton, Radley M; Bader, Daniel A; Huang, Ganlin; Sun, Qinghua; Kinney, Patrick L

2015-08-06

Because heat-related health effects tend to become more serious at higher temperatures, there is an urgent need to determine the mortality projection of specific heat-sensitive diseases to provide more detailed information regarding the variation of the sensitivity of such diseases. In this study, the specific mortality of cardiovascular and respiratory disease in Beijing was initially projected under five different global-scale General Circulation Models (GCMs) and two Representative Concentration Pathways scenarios (RCPs) in the 2020s, 2050s, and 2080s compared to the 1980s. Multi-model ensembles indicated cardiovascular mortality could increase by an average percentage of 18.4%, 47.8%, and 69.0% in the 2020s, 2050s, and 2080s under RCP 4.5, respectively, and by 16.6%,73.8% and 134% in different decades respectively, under RCP 8.5 compared to the baseline range. The same increasing pattern was also observed in respiratory mortality. The heat-related deaths under the RCP8.5 scenario were found to reach a higher number and to increase more rapidly during the 21(st) century compared to the RCP4.5 scenario, especially in the 2050s and the 2080s. The projection results show potential trends in cause-specific mortality in the context of climate change, and provide support for public health interventions tailored to specific climate-related future health risks.

Heat-related mortality projections for cardiovascular and respiratory disease under the changing climate in Beijing, China

PubMed Central

Li, Tiantian; Ban, Jie; Horton, Radley M.; Bader, Daniel A.; Huang, Ganlin; Sun, Qinghua; Kinney, Patrick L.

2015-01-01

Because heat-related health effects tend to become more serious at higher temperatures, there is an urgent need to determine the mortality projection of specific heat-sensitive diseases to provide more detailed information regarding the variation of the sensitivity of such diseases. In this study, the specific mortality of cardiovascular and respiratory disease in Beijing was initially projected under five different global-scale General Circulation Models (GCMs) and two Representative Concentration Pathways scenarios (RCPs) in the 2020s, 2050s, and 2080s compared to the 1980s. Multi-model ensembles indicated cardiovascular mortality could increase by an average percentage of 18.4%, 47.8%, and 69.0% in the 2020s, 2050s, and 2080s under RCP 4.5, respectively, and by 16.6%,73.8% and 134% in different decades respectively, under RCP 8.5 compared to the baseline range. The same increasing pattern was also observed in respiratory mortality. The heat-related deaths under the RCP8.5 scenario were found to reach a higher number and to increase more rapidly during the 21st century compared to the RCP4.5 scenario, especially in the 2050s and the 2080s. The projection results show potential trends in cause-specific mortality in the context of climate change, and provide support for public health interventions tailored to specific climate-related future health risks. PMID:26247438

Heat-related mortality projections for cardiovascular and respiratory disease under the changing climate in Beijing, China

NASA Astrophysics Data System (ADS)

Li, Tiantian; Ban, Jie; Horton, Radley M.; Bader, Daniel A.; Huang, Ganlin; Sun, Qinghua; Kinney, Patrick L.

2015-08-01

Because heat-related health effects tend to become more serious at higher temperatures, there is an urgent need to determine the mortality projection of specific heat-sensitive diseases to provide more detailed information regarding the variation of the sensitivity of such diseases. In this study, the specific mortality of cardiovascular and respiratory disease in Beijing was initially projected under five different global-scale General Circulation Models (GCMs) and two Representative Concentration Pathways scenarios (RCPs) in the 2020s, 2050s, and 2080s compared to the 1980s. Multi-model ensembles indicated cardiovascular mortality could increase by an average percentage of 18.4%, 47.8%, and 69.0% in the 2020s, 2050s, and 2080s under RCP 4.5, respectively, and by 16.6%,73.8% and 134% in different decades respectively, under RCP 8.5 compared to the baseline range. The same increasing pattern was also observed in respiratory mortality. The heat-related deaths under the RCP8.5 scenario were found to reach a higher number and to increase more rapidly during the 21st century compared to the RCP4.5 scenario, especially in the 2050s and the 2080s. The projection results show potential trends in cause-specific mortality in the context of climate change, and provide support for public health interventions tailored to specific climate-related future health risks.

The association of wildfire smoke with respiratory and cardiovascular emergency department visits in Colorado in 2012: a case crossover study.

PubMed

Alman, Breanna L; Pfister, Gabriele; Hao, Hua; Stowell, Jennifer; Hu, Xuefei; Liu, Yang; Strickland, Matthew J

2016-06-04

In 2012, Colorado experienced one of its worst wildfire seasons of the past decade. The goal of this study was to investigate the relationship of local PM2.5 levels, modeled using the Weather Research and Forecasting Model with Chemistry, with emergency department visits and acute hospitalizations for respiratory and cardiovascular outcomes during the 2012 Colorado wildfires. Conditional logistic regression was used to assess the relationship between both continuous and categorical PM2.5 and emergency department visits during the wildfire period, from June 5(th) to July 6(th) 2012. For respiratory outcomes, we observed positive relationships between lag 0 PM2.5 and asthma/wheeze (1 h max OR 1.01, 95 % CI (1.00, 1.01) per 10 μg/m(3); 24 h mean OR 1.04 95 % CI (1.02, 1.06) per 5 μg/m(3)), and COPD (1 h max OR 1.01 95 % CI (1.00, 1.02) per 10 μg/m(3); 24 h mean OR 1.05 95 % CI (1.02, 1.08) per 5 μg/m(3)). These associations were also positive for 2-day and 3-day moving average lag periods. When PM2.5 was modeled as a categorical variable, bronchitis also showed elevated effect estimates over the referent groups for lag 0 24 h average concentration. Cardiovascular results were consistent with no association. We observed positive associations between PM2.5 from wildfire and respiratory diseases, supporting evidence from previous research that wildfire PM2.5 is an important source for adverse respiratory health outcomes.

Transmission of Human Respiratory Syncytial Virus in the Immunocompromised Ferret Model

PubMed Central

de Waal, Leon; Smits, Saskia L.; Veldhuis Kroeze, Edwin J. B.; van Amerongen, Geert; Pohl, Marie O.; Osterhaus, Albert D. M. E.; Stittelaar, Koert J.

2018-01-01

Human respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with intervention strategies largely limited to infection control measures, including isolation of cases, high standards of hand hygiene, cohort nursing, and use of personal protective equipment. No vaccines against HRSV are currently available, and treatment options are largely supportive care and expensive monoclonal antibody or antiviral therapy. The limitations of current animal models for HRSV infection impede the development of new preventive and therapeutic agents, and the assessment of their potential for limiting HRSV transmission, in particular in nosocomial settings. Here, we demonstrate the efficient transmission of HRSV from immunocompromised ferrets to both immunocompromised and immunocompetent contact ferrets, with pathological findings reproducing HRSV pathology in humans. The immunocompromised ferret-HRSV model represents a novel tool for the evaluation of intervention strategies against nosocomial transmission of HRSV. PMID:29301313

Ambient temperature enhanced acute cardiovascular-respiratory mortality effects of PM2.5 in Beijing, China.

PubMed

Li, Yi; Ma, Zhiqiang; Zheng, Canjun; Shang, Yu

2015-12-01

Studies have shown that temperature could modify the effect of ambient fine particles on mortality risk. In assessing air pollution effects, temperature is usually considered as a confounder. However, ambient temperature can alter people's physiological response to air pollution and might "modify" the impact of air pollution on health outcomes. This study investigated the interaction between daily PM2.5 and daily mean temperature in Beijing, China, using data for the period 2005-2009. Bivariate PM2.5-temperature response surfaces and temperature-stratified generalized additive model (GAM) were applied to study the effect of PM2.5 on cardiovascular, respiratory mortality, and total non-accidental mortality across different temperature levels. We found that low temperature could significantly enhance the effect of PM2.5 on cardiovascular mortality. For an increase of 10 μg/m(3) in PM2.5 concentration in the lowest temperature range (-9.7∼2.6 °C), the relative risk (RR) of cardiovascular mortality increased 1.27 % (95 % CI 0.38∼2.17 %), which was higher than that of the whole temperature range (0.59 %, 95 % CI 0.22-1.16 %). The largest effect of PM2.5 on respiratory mortality appeared in the high temperature range. For an increase of 10 μg/m(3) in PM2.5 concentration, RR of respiratory mortality increased 1.70 % (95 % CI 0.92∼3.33 %) in the highest level (23.50∼31.80 °C). For the total non-accidental mortality, significant associations appeared only in low temperature levels (-9.7∼2.6 °C): for an increase of 10 μg/m(3) in current day PM2.5 concentration, RR increased 1.27 % (95 % CI 0.46∼2.00 %) in the lowest temperature level. No lag effect was observed. The results suggest that in air pollution mortality time series studies, the possibility of an interaction between air pollution and temperature should be considered.

Ambient temperature enhanced acute cardiovascular-respiratory mortality effects of PM2.5 in Beijing, China

NASA Astrophysics Data System (ADS)

Li, Yi; Ma, Zhiqiang; Zheng, Canjun; Shang, Yu

2015-12-01

Studies have shown that temperature could modify the effect of ambient fine particles on mortality risk. In assessing air pollution effects, temperature is usually considered as a confounder. However, ambient temperature can alter people's physiological response to air pollution and might "modify" the impact of air pollution on health outcomes. This study investigated the interaction between daily PM2.5 and daily mean temperature in Beijing, China, using data for the period 2005-2009. Bivariate PM2.5-temperature response surfaces and temperature-stratified generalized additive model (GAM) were applied to study the effect of PM2.5 on cardiovascular, respiratory mortality, and total non-accidental mortality across different temperature levels. We found that low temperature could significantly enhance the effect of PM2.5 on cardiovascular mortality. For an increase of 10 μg/m3 in PM2.5 concentration in the lowest temperature range (-9.7˜2.6 °C), the relative risk (RR) of cardiovascular mortality increased 1.27 % (95 % CI 0.38˜2.17 %), which was higher than that of the whole temperature range (0.59 %, 95 % CI 0.22-1.16 %). The largest effect of PM2.5 on respiratory mortality appeared in the high temperature range. For an increase of 10 μg/m3 in PM2.5 concentration, RR of respiratory mortality increased 1.70 % (95 % CI 0.92˜3.33 %) in the highest level (23.50˜31.80 °C). For the total non-accidental mortality, significant associations appeared only in low temperature levels (-9.7˜2.6 °C): for an increase of 10 μg/m3 in current day PM2.5 concentration, RR increased 1.27 % (95 % CI 0.46˜2.00 %) in the lowest temperature level. No lag effect was observed. The results suggest that in air pollution mortality time series studies, the possibility of an interaction between air pollution and temperature should be considered.

Enhancement of Antituberculosis Immunity in a Humanized Model System by a Novel Virus-Vectored Respiratory Mucosal Vaccine.

PubMed

Yao, Yushi; Lai, Rocky; Afkhami, Sam; Haddadi, Siamak; Zganiacz, Anna; Vahedi, Fatemeh; Ashkar, Ali A; Kaushic, Charu; Jeyanathan, Mangalakumari; Xing, Zhou

2017-07-01

The translation of preclinically promising novel tuberculosis vaccines to ultimate human applications has been challenged by the lack of animal models with an immune system equivalent to the human immune system in its genetic diversity and level of susceptibility to tuberculosis. We have developed a humanized mice (Hu-mice) tuberculosis model system to investigate the clinical relevance of a novel virus-vectored (VV) tuberculosis vaccine administered via respiratory mucosal or parenteral route. We find that VV vaccine activates T cells in Hu-mice as it does in human vaccinees. The respiratory mucosal route for delivery of VV vaccine in Hu-mice, but not the parenteral route, significantly reduces the humanlike lung tuberculosis outcomes in a human T-cell-dependent manner. Our results suggest that the Hu-mouse can be used to predict the protective efficacy of novel tuberculosis vaccines/strategies before they proceed to large, expensive human trials. This new vaccine testing system will facilitate the global pace of clinical tuberculosis vaccine development. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes

PubMed Central

Hassan, Sarah F.; Wearne, Travis A.; Cornish, Jennifer L.

2016-01-01

Key points Methamphetamine (METH) abuse is escalating worldwide, with the most common cause of death resulting from cardiovascular failure and hyperthermia; however, the underlying physiological mechanisms are poorly understood.Systemic administration of METH in anaesthetised rats reduced the effectiveness of some protective cardiorespiratory reflexes, increased central respiratory activity independently of metabolic function, and increased heart rate, metabolism and respiration in a pattern indicating that non‐shivering thermogenesis contributes to the well‐described hyperthermia.In animals that showed METH‐induced behavioural sensitisation following chronic METH treatment, no changes were evident in baseline cardiovascular, respiratory and metabolic measures and the METH‐evoked effects in these parameters were similar to those seen in saline‐treated or drug naïve animals.Physiological effects evoked by METH were retained but were neither facilitated nor depressed following chronic treatment with METH.These data highlight and identify potential mechanisms for targeted intervention in patients vulnerable to METH overdose. Abstract Methamphetamine (METH) is known to promote cardiovascular failure or life‐threatening hyperthermia; however, there is still limited understanding of the mechanisms responsible for evoking the physiological changes. In this study, we systematically determined the effects on both autonomic and respiratory outflows, as well as reflex function, following acute and repeated administration of METH, which enhances behavioural responses. Arterial pressure, heart rate, phrenic nerve discharge amplitude and frequency, lumbar and splanchnic sympathetic nerve discharge, interscapular brown adipose tissue and core temperatures, and expired CO2 were measured in urethane‐anaesthetised male Sprague‐Dawley rats. Novel findings include potent increases in central inspiratory drive and frequency that are not dependent on METH�

THREE-DIMENSIONAL COMPUTER MODELING OF THE HUMAN UPPER RESPIRATORY TRACT

EPA Science Inventory

ABSTRACT
Computer simulations of airflow and particle transport phenomena within the human respiratory system have important applications to aerosol therapy (e.g., the targeted delivery of inhaled drugs) and inhalation toxicology (e.g., the risk assessment of air pollutants). ...

Respiratory sinus arrhythmia stabilizes mean arterial blood pressure at high-frequency interval in healthy humans.

PubMed

Elstad, Maja; Walløe, Lars; Holme, Nathalie L A; Maes, Elke; Thoresen, Marianne

2015-03-01

Arterial blood pressure variations are an independent risk factor for end organ failure. Respiratory sinus arrhythmia (RSA) is a sign of a healthy cardiovascular system. However, whether RSA counteracts arterial blood pressure variations during the respiratory cycle remains controversial. We restricted normal RSA with non-invasive intermittent positive pressure ventilation (IPPV) to test the hypothesis that RSA normally functions to stabilize mean arterial blood pressure. Ten young volunteers were investigated during metronome-paced breathing and IPPV. Heart rate (ECG), mean arterial blood pressure and left stroke volume (finger arterial pressure curve) and right stroke volume (pulsed ultrasound Doppler) were recorded, while systemic and pulmonary blood flow were calculated beat-by-beat. Respiratory variations (high-frequency power, 0.15-0.40 Hz) in cardiovascular variables were estimated by spectral analysis. Phase angles and correlation were calculated by cross-spectral analysis. The magnitude of RSA was reduced from 4.9 bpm(2) (95% CI 3.0, 6.2) during metronome breathing to 2.8 bpm(2) (95% CI 1.1, 5.0) during IPPV (p = 0.03). Variations in mean arterial blood pressure were greater (2.3 mmHg(2) (95% CI 1.4, 3.9) during IPPV than during metronome breathing (1.0 mmHg(2) [95% CI 0.7, 1.3]) (p = 0.014). Respiratory variations in right and left stroke volumes were inversely related in the respiratory cycle during both metronome breathing and IPPV. RSA magnitude is lower and mean arterial blood pressure variability is greater during IPPV than during metronome breathing. We conclude that in healthy humans, RSA stabilizes mean arterial blood pressure at respiratory frequency.

Numerical simulation of migration behavior of uranium ore dust particles in the human respiratory tract

NASA Astrophysics Data System (ADS)

Ye, Yong-jun; Yin, An-song; Li, Zhi; Lei, Bo; Ding, De-xin

2017-04-01

There is a certain concentration of radioactive dust particles in the air of workplace of underground uranium mines. Some small diameter particles will pass through the masks and enter the respiratory tract which will cause radiation damage to the human body. In order to study deposition regularity of uranium dust in the human respiratory tract, in this paper, we firstly use the RNG turbulence model to simulate the gas flow field in the human respiratory tract Z0 ∼ Z3 level under different respiratory intensity. Then we use DPM discrete phase model to simulate the concentration, particle size distribution, deposition rate and deposition share of uranium dust particles after being filtered through the masks in the human respiratory tract Z0 to Z3 bronchus. According to the simulation results, we have got the following conclusions: the particles’ number concentration of uranium dust after being filtered through the mask in the human respiratory tract basically decreases with the increasing of particle size under different respiratory intensities on the environment of uranium mine. In addition, the intensity of respiration and the mass concentration of particles have an important influence on the deposition rate and the deposition of particles in the respiratory tract.

Heat-Related Mortality Projections for Cardiovascular and Respiratory Disease Under the Changing Climate in Beijing, China

NASA Technical Reports Server (NTRS)

Li, Tiantian; Ban, Jie; Horton, Radley M.; Bader, Daniel A.; Huang, Ganlin; Sun, Qinghua; Kinney, Patrick L.

2015-01-01

Because heat-related health effects tend to become more serious at higher temperatures, there is an urgent need to determine the mortality projection of specific heat-sensitive diseases to provide more detailed information regarding the variation of the sensitivity of such diseases. In this study, the specific mortality of cardiovascular and respiratory disease in Beijing was initially projected under five different global-scale General Circulation Models (GCMs) and two Representative Concentration Pathways scenarios (RCPs) in the 2020s, 2050s, and 2080s compared to the 1980s. Multi-model ensembles indicated cardiovascular mortality could increase by an average percentage of 18.4 percent, 47.8 percent, and 69.0 percent in the 2020s, 2050s, and 2080s under RCP 4.5, respectively, and by 16.6 percent, 73.8 percent and 134 percent in different decades respectively, under RCP 8.5 compared to the baseline range. The same increasing pattern was also observed in respiratory mortality. The heat-related deaths under the RCP 8.5 scenario were found to reach a higher number and to increase more rapidly during the 21st century compared to the RCP4.5 scenario, especially in the 2050s and the 2080s. The projection results show potential trends in cause-specific mortality in the context of climate change, and provide support for public health interventions tailored to specific climate-related future health risks.

Assessment of the Possible Association of Air Pollutants PM10, O3, NO2 With an Increase in Cardiovascular, Respiratory, and Diabetes Mortality in Panama City: A 2003 to 2013 Data Analysis.

PubMed

Zúñiga, Julio; Tarajia, Musharaf; Herrera, Víctor; Urriola, Wilfredo; Gómez, Beatriz; Motta, Jorge

2016-01-01

In recent years, Panama has experienced a marked economic growth, and this, in turn, has been associated with rapid urban development and degradation of air quality. This study is the first evaluation done in Panama on the association between air pollution and mortality. Our objective was to assess the possible association between monthly levels of PM10, O3, and NO2, and cardiovascular, respiratory, and diabetes mortality, as well as the seasonal variation of mortality in Panama City, Panama.The study was conducted in Panama City, using air pollution data from January 2003 to December 2013. We utilized a Poisson regression model based on generalized linear models, to evaluate the association between PM10, NO2, and O3 exposure and mortality from diabetes, cardiovascular, and respiratory diseases. The sample size for PM10, NO2, and O2 was 132, 132, and 108 monthly averages, respectively.We found that levels of PM10, O3, and NO2 were associated with increases in cardiovascular, respiratory, and diabetes mortality. For PM10 levels ≥ 40 μg/m3, we found an increase in cardiovascular mortality of 9.7% (CI 5.8-13.6%), and an increase of 12.6% (CI 0.2-24.2%) in respiratory mortality. For O3 levels ≥ 20 μg/m3 we found an increase of 32.4% (IC 14.6-52.9) in respiratory mortality, after a 2-month lag period following exposure in the 65 to <74 year-old age group. For NO2 levels ≥20 μg/m3 we found an increase in respiratory mortality of 11.2% (IC 1.9-21.3), after a 2-month lag period following exposure among those aged between 65 and <74 years.There could be an association between the air pollution in Panama City and an increase in cardiovascular, respiratory, and diabetes mortality. This study confirms the urgent need to improve the measurement frequency of air pollutants in Panama.

Assessing the effects of the Spanish partial smoking ban on cardiovascular and respiratory diseases: methodological issues.

PubMed

Galán, Iñaki; Simón, Lorena; Flores, Víctor; Ortiz, Cristina; Fernández-Cuenca, Rafael; Linares, Cristina; Boldo, Elena; Medrano, María José; Pastor-Barriuso, Roberto

2015-12-01

Recent research has assessed the impact of tobacco laws on cardiovascular and respiratory morbidity. In this study, we also examined whether the association between the implementation of the 2005 Spanish smoking ban and hospital admissions for cardiovascular and respiratory diseases varies according to the adjustment for potential confounders. Ecological time series analysis. Residents of Madrid and Barcelona cities (Spain). Data on daily emergency room admissions for acute myocardial infarction, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), and asthma derived from the 2003-2006 Spanish hospital admissions registry. Changes in admission rates between 2006 and the 2003-2005 period were estimated using additive Poisson models allowing for overdispersion adjusted for secular trend in admission, seasonality, day of the week, temperature, number of flu and acute respiratory infection cases, pollution levels, tobacco consumption prevalence and, for asthma cases, pollen count. In Madrid, fully adjusted models failed to detect significant changes in hospital admission rates for any disease during the study period. In Barcelona, however, hospital admissions decreased by 10.2% (95% CI 3.8% to 16.1%) for cerebrovascular diseases and by 16.0% (95% CI 7.0% to 24.1%) for COPD. Substantial changes in effect estimates were observed on adjustment for linear or quadratic trend. Effect estimates for asthma-related admissions varied substantially when adjusting for pollen count in Madrid, and for seasonality and tobacco consumption in Barcelona. Our results confirm that the potential impact of a smoking ban must be adjusted for the underlying secular trend. In asthma-related admissions, pollen count, seasonality and tobacco consumption must be specified in the model. The substantial variability in effects detected between the two cities of Madrid and Barcelona lends strong support for a nationwide study to assess the overall effect of a smoking ban in Spain

[Atmospheric pollution and cardiovascular damage].

PubMed

Román, Oscar; Prieto, María José; Mancilla, Pedro

2004-06-01

The damaging effect of atmospheric pollution with particulate matter and toxic gases on the respiratory system and its effect in the incidence and severity of respiratory diseases, is well known. A similar effect on the cardiovascular system is currently under investigation. Epidemiological studies have demonstrated that the inhalation of particulate matter can increase cardiovascular disease incidence and mortality, specially ischemic heart disease. The damage would be mediated by alterations in the autonomic nervous system, inflammation, infections and free radicals. In human studies, environmental pollution is associated with alterations in cardiac frequency variability and blood pressure and with changes in ventricular repolarization. Experimentally, an enhancement of ischemia, due to coronary obstruction, has been demonstrated. The study of the toxic effects of environmental pollution over the cardiovascular system, is an open field, specially in Chile, were the big cities have serious contamination problems.

Human herpesviruses respiratory infections in patients with acute respiratory distress (ARDS).

PubMed

Bonizzoli, Manuela; Arvia, Rosaria; di Valvasone, Simona; Liotta, Francesco; Zakrzewska, Krystyna; Azzi, Alberta; Peris, Adriano

2016-08-01

Acute respiratory distress syndrome (ARDS) is today a leading cause of hospitalization in intensive care unit (ICU). ARDS and pneumonia are closely related to critically ill patients; however, the etiologic agent is not always identified. The presence of human herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus in respiratory samples of critically ill patients is increasingly reported even without canonical immunosuppression. The main aim of this study was to better understand the significance of herpesviruses finding in lower respiratory tract of ARDS patients hospitalized in ICU. The presence of this group of herpesviruses, in addition to the research of influenza viruses and other common respiratory viruses, was investigated in respiratory samples from 54 patients hospitalized in ICU, without a known microbiological causative agent. Moreover, the immunophenotype of each patient was analyzed. Herpesviruses DNA presence in the lower respiratory tract seemed not attributable to an impaired immunophenotype, whereas a significant correlation was observed between herpesviruses positivity and influenza virus infection. A higher ICU mortality was significantly related to the presence of herpesvirus infection in the lower respiratory tract as well as to impaired immunophenotype, as patients with poor outcome showed severe lymphopenia, affecting in particular T (CD3+) cells, since the first days of ICU hospitalization. In conclusion, these results indicate that herpesviruses lower respiratory tract infection, which occurs more frequently following influenza virus infection, can be a negative prognostic marker. An independent risk factor for ICU patients with ARDS is an impaired immunophenotype.

FLOW SIMULATION IN THE HUMAN UPPER RESPIRATORY TRACT

EPA Science Inventory

ABSTRACT

Computer simulations of airflow patterns within the human upper respiratory tract (URT) are presented. The URT model includes airways of the head (nasal and oral), throat (pharyngeal and laryngeal), and lungs (trachea and main bronchi). The head and throat mor...

Wave processes in the human cardiovascular system: The measuring complex, computing models, and diagnostic analysis

NASA Astrophysics Data System (ADS)

Ganiev, R. F.; Reviznikov, D. L.; Rogoza, A. N.; Slastushenskiy, Yu. V.; Ukrainskiy, L. E.

2017-03-01

A description of a complex approach to investigation of nonlinear wave processes in the human cardiovascular system based on a combination of high-precision methods of measuring a pulse wave, mathematical methods of processing the empirical data, and methods of direct numerical modeling of hemodynamic processes in an arterial tree is given.

3-D PARTICLE TRANSPORT WITHIN THE HUMAN UPPER RESPIRATORY TRACT

EPA Science Inventory

In this study trajectories of inhaled particulate matter (PM) were simulated within a three-dimensional (3-D) computer model of the human upper respiratory tract (URT). The airways were described by computer-reconstructed images of a silicone rubber cast of the human head, throat...

DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

NASA Technical Reports Server (NTRS)

Hester, Robert L.; Summers, Richard L.; lIescu, Radu; Esters, Joyee; Coleman, Thomas G.

2010-01-01

Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

Cardiovascular oscillations: in search of a nonlinear parametric model

NASA Astrophysics Data System (ADS)

Bandrivskyy, Andriy; Luchinsky, Dmitry; McClintock, Peter V.; Smelyanskiy, Vadim; Stefanovska, Aneta; Timucin, Dogan

2003-05-01

We suggest a fresh approach to the modeling of the human cardiovascular system. Taking advantage of a new Bayesian inference technique, able to deal with stochastic nonlinear systems, we show that one can estimate parameters for models of the cardiovascular system directly from measured time series. We present preliminary results of inference of parameters of a model of coupled oscillators from measured cardiovascular data addressing cardiorespiratory interaction. We argue that the inference technique offers a very promising tool for the modeling, able to contribute significantly towards the solution of a long standing challenge -- development of new diagnostic techniques based on noninvasive measurements.

Cardiovascular Adaptations Induced by Resistance Training in Animal Models.

PubMed

Melo, S F S; da Silva Júnior, N D; Barauna, V G; Oliveira, E M

2018-01-01

In the last 10 years the number of studies showing the benefits of resistance training (RT) to the cardiovascular system, have grown. In comparison to aerobic training, RT-induced favorable adaptations to the cardiovascular system have been ignored for many years, thus the mechanisms of the RT-induced cardiovascular adaptations are still uncovered. The lack of animal models with comparable protocols to the RT performed by humans hampers the knowledge. We have used squat-exercise model, which is widely used by many others laboratories. However, to a lesser extent, other models are also employed to investigate the cardiovascular adaptations. In the subsequent sections we will review the information regarding cardiac morphological adaptations, signaling pathway of the cardiac cell, cardiac function and the vascular adaptation induced by RT using this animal model developed by Tamaki et al. in 1992. Furthermore, we also describe cardiovascular findings observed using other animal models of RT.

Biomechanical investigation of different surgical strategies for the treatment of rib fractures using a three-dimensional human respiratory model.

PubMed

Shih, Kao-Shang; Truong, Thanh An; Hsu, Ching-Chi; Hou, Sheng-Mou

2017-11-02

Rib fracture is a common injury and can result in pain during respiration. Conservative treatment of rib fracture is applied via mechanical ventilation. However, ventilator-associated complications frequently occur. Surgical fixation is another approach to treat rib fractures. Unfortunately, this surgical treatment is still not completely defined. Past studies have evaluated the biomechanics of the rib cage during respiration using a finite element method, but only intact conditions were modelled. Thus, the purpose of this study was to develop a realistic numerical model of the human rib cage and to analyse the biomechanical performance of intact, injured and treated rib cages. Three-dimensional finite element models of the human rib cage were developed. Respiratory movement of the human rib cage was simulated to evaluate the strengths and limitations of different scenarios. The results show that a realistic human respiratory movement can be simulated and the predicted results were closely related to previous study (correlation coefficient>0.92). Fixation of two fractured ribs significantly decreased the fixation index (191%) compared to the injured model. This fixation may provide adequate fixation stability as well as reveal lower bone stress and implant stress compared with the fixation of three or more fractured ribs.

Evaluation of exercise-respiratory system modifications and integration schemes for physiological systems

NASA Technical Reports Server (NTRS)

Gallagher, R. R.

1974-01-01

Exercise subroutine modifications are implemented in an exercise-respiratory system model yielding improvement of system response to exercise forcings. A more physiologically desirable respiratory ventilation rate in addition to an improved regulation of arterial gas tensions and cerebral blood flow is observed. A respiratory frequency expression is proposed which would be appropriate as an interfacing element of the respiratory-pulsatile cardiovascular system. Presentation of a circulatory-respiratory system integration scheme along with its computer program listing is given. The integrated system responds to exercise stimulation for both nonstressed and stressed physiological states. Other integration possibilities are discussed with respect to the respiratory, pulsatile cardiovascular, thermoregulatory, and the long-term circulatory systems.

Long-Term PM2.5 Exposure and Respiratory, Cancer, and Cardiovascular Mortality in Older US Adults.

PubMed

Pun, Vivian C; Kazemiparkouhi, Fatemeh; Manjourides, Justin; Suh, Helen H

2017-10-15

The impact of chronic exposure to fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5)) on respiratory disease and lung cancer mortality is poorly understood. In a cohort of 18.9 million Medicare beneficiaries (4.2 million deaths) living across the conterminous United States between 2000 and 2008, we examined the association between chronic PM2.5 exposure and cause-specific mortality. We evaluated confounding through adjustment for neighborhood behavioral covariates and decomposition of PM2.5 into 2 spatiotemporal scales. We found significantly positive associations of 12-month moving average PM2.5 exposures (per 10-μg/m3 increase) with respiratory, chronic obstructive pulmonary disease, and pneumonia mortality, with risk ratios ranging from 1.10 to 1.24. We also found significant PM2.5-associated elevated risks for cardiovascular and lung cancer mortality. Risk ratios generally increased with longer moving averages; for example, an elevation in 60-month moving average PM2.5 exposures was linked to 1.33 times the lung cancer mortality risk (95% confidence interval: 1.24, 1.40), as compared with 1.13 (95% confidence interval: 1.11, 1.15) for 12-month moving average exposures. Observed associations were robust in multivariable models, although evidence of unmeasured confounding remained. In this large cohort of US elderly, we provide important new evidence that long-term PM2.5 exposure is significantly related to increased mortality from respiratory disease, lung cancer, and cardiovascular disease. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cardiovascular Deconditioning in Humans: Human Studies Core

NASA Technical Reports Server (NTRS)

Williams, Gordon

1999-01-01

Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

Mathematical modelling of flow distribution in the human cardiovascular system

NASA Technical Reports Server (NTRS)

Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

1992-01-01

The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes.

Chest associated to motor physiotherapy improves cardiovascular variables in newborns with respiratory distress syndrome

PubMed Central

2011-01-01

Background We aimed to evaluate the effects of chest and motor physiotherapy treatment on hemodynamic variables in preterm newborns with respiratory distress syndrome. Methods We evaluated heart rate (HR), respiratory rate (RR), systolic (SAP), mean (MAP) and diastolic arterial pressure (DAP), temperature and oxygen saturation (SO2%) in 44 newborns with respiratory distress syndrome. We compared all variables between before physiotherapy treatment vs. after the last physiotherapy treatment. Newborns were treated during 11 days. Variables were measured 2 minutes before and 5 minutes after each physiotherapy treatment. We applied paired Student t test to compare variables between the two periods. Results HR (148.5 ± 8.5 bpm vs. 137.1 ± 6.8 bpm - p < 0.001), SAP (72.3 ± 11.3 mmHg vs. 63.6 ± 6.7 mmHg - p = 0.001) and MAP (57.5 ± 12 mmHg vs. 47.7 ± 5.8 mmHg - p = 0.001) were significantly reduced after 11 days of physiotherapy treatment compared to before the first session. There were no significant changes regarding RR, temperature, DAP and SO2%. Conclusions Chest and motor physiotherapy improved cardiovascular parameters in respiratory distress syndrome newborns. PMID:22029840

Deposition of naphthalene and tetradecane vapors in models of the human respiratory system.

PubMed

Zhang, Zhe; Kleinstreuer, Clement

2011-01-01

Jet-propulsion fuel (particularly JP-8) is currently being used worldwide, exposing especially Air Force personnel and people living near airfields to JP-8 vapors and aerosols during aircraft fueling, maintenance operations, and/or cold starts. JP-8 is a complex mixture containing >200, mostly toxic, aliphatic and aromatic hydrocarbon compounds of which tetradecane and naphthalene were chosen as two representative chemical markers for computer simulations. Thus, transport and deposition of naphthalene and tetradecane vapors have been simulated in models of the human respiratory system. The inspiratory deposition data were analyzed in terms of regional deposition fractions (DFs) and deposition enhancement factors (DEF). The vapor depositions are affected by vapor properties (e.g. diffusivity), airway geometric features, breathing patterns, inspiratory flow rates, as well as airway-wall absorption parameter. Specifically, the respiratory uptake of vapors is greatly influenced by the degree of airway-wall absorption. For example, being an almost insoluble species in the mucus layer, the deposition of tetradecane vapor is nearly zero in the extrathoracic and tracheobronchial (TB) airways, that is, the DF is <1%. The remaining vapors may penetrate further and deposit in the alveolar airways. The DF of tetradecane vapors during inhalation in the alveolar region can range from 7% to 24%, depending on breathing waveform, inhalation rate, and thickness of the mucus layer. In contrast, naphthalene vapor almost completely deposits in the extrathoracic and TB airways and hardly moves downstream and deposits in the respiratory zone. The DFs of naphthalene vapor in the extrathoracic airways from nasal/oral to trachea under normal breathing conditions (Q = 15-60 L/min) are about 12-34%, although they are about 66-87% in the TB airways. In addition, the variation of breathing routes (say, from nasal breathing to oral breathing) may influence the vapor deposition in the

Willingness to pay for improved respiratory and cardiovascular health: a multiple-format, stated-preference approach.

PubMed

Johnson, F R; Banzhaf, M R; Desvousges, W H

2000-06-01

This study uses stated-preference (SP) analysis to measure willingness to pay (WTP) to reduce acute episodes of respiratory and cardiovascular ill health. The SP survey employs a modified version of the health state descriptions used in the Quality of Well Being (QWB) Index. The four health state attributes are symptom, episode duration, activity restrictions and cost. Preferences are elicited using two different SP formats: graded-pair and discrete-choice. The different formats cause subjects to focus on different evaluation strategies. Combining two elicitation formats yields more valid and robust estimates than using only one approach. Estimates of indirect utility function parameters are obtained using advanced panel econometrics for each format separately and jointly. Socio-economic differences in health preferences are modelled by allowing the marginal utility of money relative to health attributes to vary across respondents. Because the joint model captures the combined preference information provided by both elicitation formats, these model estimates are used to calculate WTP. The results demonstrate the feasibility of estimating meaningful WTP values for policy-relevant respiratory and cardiac symptoms, even from subjects who never have personally experienced these conditions. Furthermore, because WTP estimates are for individual components of health improvements, estimates can be aggregated in various ways depending upon policy needs. Thus, using generic health attributes facilitates transferring WTP estimates for benefit-cost analysis of a variety of potential health interventions. Copyright 2000 John Wiley & Sons, Ltd.

Respiratory, cardiovascular and other physiological consequences of smoking cessation.

PubMed

Gratziou, Christina

2009-02-01

Smoking cessation is associated with substantial reductions in tobacco-related morbidity and mortality. Based on the current literature, the beneficial effects of quitting are particularly evident on pulmonary and cardiovascular function, but the negative physiological effects of cessation are less well documented. The objective of this article was to review systematically data on the physiological effects of smoking cessation. Articles based upon clinical trials, randomised controlled trials and meta-analyses were selected from titles and abstracts obtained via a MEDLINE search (May 2003-May 2008). Additional studies were identified from the bibliographies of reviewed literature. Smoking cessation is associated with improved lung function and a reduction in the presence and severity of respiratory symptoms. These changes, apparent within months of quitting, are sustained with long-term abstinence. The underlying pathophysiologies of smoking-induced airway inflammation and endothelial dysfunction are partially reversed following cessation in healthy ex-smokers, but not in those with chronic obstructive pulmonary disease. Smoking cessation is also associated with substantially improved cardiovascular function and reduced risk of primary and secondary cardiovascular morbidity and mortality. Although the overall long-term health benefits are unquestionable, smoking cessation is also associated with other possible undesirable short-term physiological effects such as weight gain, hypertension, constipation and mouth ulcers; and altered activity of the enzyme cytochrome P450 1A2 (CYP1A2), which metabolises many commonly used drugs. The negative physiological effects of smoking cessation may adversely affect a smoker's attempt to quit, and physicians should provide their smoking patients with motivation and regular encouragement and support when attempting to quit, whilst educating them on the health benefits of abstinence. Additionally, since cigarette smoke is a potent

Impact of improved insulation and heating on mortality risk of older cohort members with prior cardiovascular or respiratory hospitalisations.

PubMed

Preval, Nicholas; Keall, Michael; Telfar-Barnard, Lucy; Grimes, Arthur; Howden-Chapman, Philippa

2017-11-14

We carried out an evaluation of a large-scale New Zealand retrofit programme using administrative data that provided the statistical power to assess the effect of insulation and/or heating retrofits on cardiovascular and respiratory-related mortality in people aged 65 and over with prior respiratory or circulatory hospitalisations. Quasi-experimental cohort study based on administrative data. New Zealand. From a larger study cohort of over 900 000 people, we selected two subcohorts: 3287 people who were aged 65 and over and had experienced pretreatment period cardiovascular-related hospitalisation (ICD-10 chapter 9), and 1561 people aged 65 and over who had experienced pretreatment respiratory-related hospitalisation (ICD-10 chapter 10). Treatment group individuals lived in a home that received insulation and/or heating retrofits under the Warm Up New Zealand: Heat Smart programme. Control group individuals lived in a home that was matched to a treatment home based on physical characteristics and location. HR for all-cause mortality for treatment with insulation, heating, or insulation and heating relative to control group. People with pretreatment circulatory hospitalisation who occupied a household that received only insulation had an HR for all-cause mortality of 0.673 (95% CI 0.535 to 0.847) (p<0.001) relative to control group members. Individuals with a pretreatment respiratory hospitalisation who occupied a household that received only an insulation retrofit had an HR for all-cause mortality of 0.830 (95% CI 0.655 to 1.051) (p=0.122) relative to control group members. There was no evidence of an additional benefit from receiving heating. We interpret the hazard rate observed for cardiovascular subcohort individuals who received insulation as evidence of a protective effect, reducing the risk of mortality for vulnerable older adults. There is suggestive evidence of a protective effect of insulation for the respiratory subcohort. © Article author(s) (or

Impact of improved insulation and heating on mortality risk of older cohort members with prior cardiovascular or respiratory hospitalisations

PubMed Central

Keall, Michael; Telfar-Barnard, Lucy; Grimes, Arthur; Howden-Chapman, Philippa

2017-01-01

Objectives We carried out an evaluation of a large-scale New Zealand retrofit programme using administrative data that provided the statistical power to assess the effect of insulation and/or heating retrofits on cardiovascular and respiratory-related mortality in people aged 65 and over with prior respiratory or circulatory hospitalisations. Design Quasi-experimental cohort study based on administrative data. Setting New Zealand. Participants From a larger study cohort of over 900 000 people, we selected two subcohorts: 3287 people who were aged 65 and over and had experienced pretreatment period cardiovascular-related hospitalisation (ICD-10 chapter 9), and 1561 people aged 65 and over who had experienced pretreatment respiratory-related hospitalisation (ICD-10 chapter 10). Interventions Treatment group individuals lived in a home that received insulation and/or heating retrofits under the Warm Up New Zealand: Heat Smart programme. Control group individuals lived in a home that was matched to a treatment home based on physical characteristics and location. Primary and secondary outcome measures HR for all-cause mortality for treatment with insulation, heating, or insulation and heating relative to control group. Results People with pretreatment circulatory hospitalisation who occupied a household that received only insulation had an HR for all-cause mortality of 0.673 (95% CI 0.535 to 0.847) (p<0.001) relative to control group members. Individuals with a pretreatment respiratory hospitalisation who occupied a household that received only an insulation retrofit had an HR for all-cause mortality of 0.830 (95% CI 0.655 to 1.051) (p=0.122) relative to control group members. There was no evidence of an additional benefit from receiving heating. Conclusions We interpret the hazard rate observed for cardiovascular subcohort individuals who received insulation as evidence of a protective effect, reducing the risk of mortality for vulnerable older adults. There is

Effect of Age on Complexity and Causality of the Cardiovascular Control: Comparison between Model-Based and Model-Free Approaches

PubMed Central

Porta, Alberto; Faes, Luca; Bari, Vlasta; Marchi, Andrea; Bassani, Tito; Nollo, Giandomenico; Perseguini, Natália Maria; Milan, Juliana; Minatel, Vinícius; Borghi-Silva, Audrey; Takahashi, Anielle C. M.; Catai, Aparecida M.

2014-01-01

The proposed approach evaluates complexity of the cardiovascular control and causality among cardiovascular regulatory mechanisms from spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and respiration (RESP). It relies on construction of a multivariate embedding space, optimization of the embedding dimension and a procedure allowing the selection of the components most suitable to form the multivariate embedding space. Moreover, it allows the comparison between linear model-based (MB) and nonlinear model-free (MF) techniques and between MF approaches exploiting local predictability (LP) and conditional entropy (CE). The framework was applied to study age-related modifications of complexity and causality in healthy humans in supine resting (REST) and during standing (STAND). We found that: 1) MF approaches are more efficient than the MB method when nonlinear components are present, while the reverse situation holds in presence of high dimensional embedding spaces; 2) the CE method is the least powerful in detecting age-related trends; 3) the association of HP complexity on age suggests an impairment of cardiac regulation and response to STAND; 4) the relation of SAP complexity on age indicates a gradual increase of sympathetic activity and a reduced responsiveness of vasomotor control to STAND; 5) the association from SAP to HP on age during STAND reveals a progressive inefficiency of baroreflex; 6) the reduced connection from HP to SAP with age might be linked to the progressive exploitation of Frank-Starling mechanism at REST and to the progressive increase of peripheral resistances during STAND; 7) at REST the diminished association from RESP to HP with age suggests a vagal withdrawal and a gradual uncoupling between respiratory activity and heart; 8) the weakened connection from RESP to SAP with age might be related to the progressive increase of left ventricular thickness and vascular stiffness and to the gradual decrease of

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

PubMed Central

Sharma, Anurag; Wu, Wenzhu; Sung, Biin; Huang, Jing; Tsao, Tiffany; Li, Xiangming; Gomi, Rika; Tsuji, Moriya

2016-01-01

ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4+ T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1β (IL-1β) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. IMPORTANCE Infections with respiratory syncytial virus (RSV) are common and can cause severe lung disease in infants and the elderly. The lack of a suitable animal model with disease features similar to those in humans has hampered efforts to predict the efficacy of novel anti-RSV therapies and

Carbon Nanotubes in the Human Respiratory Tract-Clearance Modeling.

PubMed

Sturm, Robert

2017-03-01

Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system. Clearance velocities were expressed by respective clearance half-times ranging from several hours in the case of fast clearance to tens of days in the case of slow clearance. Results of the simulations clearly demonstrate that for the specific deposition scenario (sitting, nasal breathing) considered here fast clearance fraction exhibits a slight decrease with increasing age, but total clearance times (i.e. time spans, within which 100% of the deposited particulate mass are removed) are rather constant among the age groups. Nanotubes deposited in the respiratory bronchioles and alveoli are usually subject to a long-term storage in these structures and, thus, may trigger malignant transformations in adjacent cells and tissues. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

OZONE-INDUCED RESPIRATORY SYMPTOMS AND LUNG FUNCTION DECREMENTS IN HUMANS: EXPOSURE-RESPONSE MODELS

EPA Science Inventory

Short duration exposure to ozone (<8 hr) is known to result in lung function decrements and respiratory symptoms in humans. The magnitudes of these responses are functions of ozone concentration (C), activity level measured by minute ventilation (Ve), duration of exposure (T), a...

Particle deposition and clearance of atmospheric particles in the human respiratory tract during LACE 98

NASA Astrophysics Data System (ADS)

Bundke, U.; Hänel, G.

2003-04-01

During the LACE 98footnote{Lindenberg Aerosol Characterization Experiment, (Germany) 1998} experiment microphysical, chemical and optical properties of atmospheric particles were measured by several groups. (Bundke et al.). The particle deposition and clearance of the particles in the human respiratory tract was calculated using the ICRP (International Commission on Radiological Protection) deposition and clearance model (ICRP 1994). Particle growth as function of relative humidity outside the body was calculated from measurement data using the model introduced by Bundke et al.. Particle growth inside the body was added using a non-equilibrium particle growth model. As a result of the calculations, time series of the total dry particle mass and -size distribution were obtained for all compartments of the human respiratory tract defined by ICRP 1994. The combined ICRP deposition and clearance model was initialized for different probationers like man, woman, children of different ages and several circumstances like light work, sitting, sleeping etc. Keeping the conditions observed during LACE 98 constant a approximation of the aerosol burdens of the different compartments was calculated up to 4 years of exposure and compared to the results from Snipes et al. for the "Phoenix" and "Philadelphia" aerosol. References: footnotesize{ Bundke, U. et al.,it{Aerosol Optical Properties during the Lindenberg Aerosol Characterization Experiment (LACE 98)} ,10.1029/2000JD000188, JGR, 2002 ICRP,it{Human Respiratory Tract Model for Radiological Protection, Bd. ICRP Publication 66}, Annals of the ICRP, 24,1-3, Elsevier Science, Ocford, 1994 Snipes et al. ,it{The 1994 ICRP66 Human Respiratory Tract Model as a Tool for predicting Lung Burdens from Exposure to Environmental Aerosols}, Appl. Occup. Environ. Hyg., 12, 547-553,1997}

Investigations of the Cardiovascular and Respiratory Systems on Board the International Space Station: Experiments Puls and Pneumocard

NASA Astrophysics Data System (ADS)

Baranov, V. M.; Baevsky, R. M.; Drescher, J.; Tank, J.

parameters describing the results of the function of these systems like heart rate, arterial pressure, cardiac output, or breathing frequency, concentration of O2 and CO2 , etc. Missing significant changes of these parameters during weightlessness supports the hypothesis that adaptational and compensatory mechanisms are sufficient and guarantee cardiovascular homeostasis under changing environmental conditions. characteristic changes of the vegetative balance and of the activity of different regulatory elements at the brainstem and subcortical level. This changes guaranteed the adaptation to long term weightlessness. However, it remains unclear to what extent the different levels are involved. Moreover, the criteria describing the efficacy of cardiorespiratory interaction for the different functional states are not defined yet. The investigation of this problems is highly relevant in order to improve the medical control, especially if considering that the disruption of regulatory systems mostly precedes dangerous destruction of homeostasis. cardiovascular and respiratory function on Board the International Space Station (ISS) aiming to obtain new insights into the interaction between different regulatory elements. "Puls" is measures ECG, photoplethysmogram (PPG), and the pneumotachogram (PTG). The ECG is used to measure time series of R-R intervals and to analyse HRV. PPG is used to define the pulse wave velocity, phases of the cardiac cycle, and an estimate of the filling of finger vessels. The variability of these parameters is also calculated and compared to HRV. The analysis of the PTG allows to describe the interaction of the regulatory parameters of the cardiovascular and respiratory systems. Hence, an important feature of the experiment "Puls" is the investigation of regulatory mechanisms rather than of cardiovascular homeostasis. cardiography) and left ventricular contractility (seismocardiography) will be obtained. This expansion is of major importance

Structure and interactions of human respiratory mucin

NASA Astrophysics Data System (ADS)

Purdy, Kirstin; Sheehan, John; Rubinstein, Michael; Wong, Gerard

2006-03-01

Human respiratory mucin plays a crucial role in the pathology of Cystic Fibrosis lung infections. Mucin is a flexible, linear polyelectrolyte, characterized by its many charged oligo-carbohydrate side chains that give it its bottle-brush structure. The macroscopic properties of a mucin suspension are known to change drastically with changes in ion concentration and solution pH, but little is known about the effect of these variables on individual mucin structure. We present preliminary results on the structural response of individual human respiratory mucin molecules to variations in concentration of ions of different valences via small angle x-ray diffraction.

Needs for animal models of human diseases of the respiratory system.

PubMed Central

Reid, L. M.

1980-01-01

Animal models are of two types those that occur spontaneously and those that the scientist produces by artefact. One value of spontaneously occurring models is that if pathogenetic mechanisms are identified, they give new leads for the study of human disease. There is a need for spontaneously occurring examples of so-called primary or idiopathic pulmonary fibrosis, pulmonary hypertension (arterial or venous), and emphysema. Acquired or artefactual models of each of these conditions are available and have led to better understanding of the pathological changes, but they have not led to identification of the basic or primary abnormality. A naturally occurring model of cystic fibrosis could be a major event in our control of this disease. A spontaneously occurring form of asthma is needed as a bridge between experiment and patient. Artefactual models that are needed are of bronchopulmonary dysplasia and shock lung. There is probably enough agreement--but only just--on the nature of bronchopulmonary dysplasia for specific needs to be identified. Here the questions concern the choice of an appropriate species--or several--in which to study the premature lung and its adaptation to air breathing and supportive therapy. Knowledge of comparative anatomy and physiology must influence choice of species for certain models. For adult respiratory failure, or shock lung, a model is needed that progresses to pulmonary hypertension. Spontaneous models of interstitial pneumonia and of infection, both viral and bacterial, are needed. An animal model of a disease is only as useful as the questions we ask of it. PMID:6969987

Productive Infection of Human Embryonic Stem Cell-Derived NKX2.1+ Respiratory Progenitors with Human Rhinovirus.

PubMed

Jenny, Robert A; Hirst, Claire; Lim, Sue Mei; Goulburn, Adam L; Micallef, Suzanne J; Labonne, Tanya; Kicic, Anthony; Ling, Kak-Ming; Stick, Stephen M; Ng, Elizabeth S; Trounson, Alan; Giudice, Antonietta; Elefanty, Andrew G; Stanley, Edouard G

2015-06-01

Airway epithelial cells generated from pluripotent stem cells (PSCs) represent a resource for research into a variety of human respiratory conditions, including those resulting from infection with common human pathogens. Using an NKX2.1-GFP reporter human embryonic stem cell line, we developed a serum-free protocol for the generation of NKX2.1(+) endoderm that, when transplanted into immunodeficient mice, matured into respiratory cell types identified by expression of CC10, MUC5AC, and surfactant proteins. Gene profiling experiments indicated that day 10 NKX2.1(+) endoderm expressed markers indicative of early foregut but lacked genes associated with later stages of respiratory epithelial cell differentiation. Nevertheless, NKX2.1(+) endoderm supported the infection and replication of the common respiratory pathogen human rhinovirus HRV1b. Moreover, NKX2.1(+) endoderm upregulated expression of IL-6, IL-8, and IL-1B in response to infection, a characteristic of human airway epithelial cells. Our experiments provide proof of principle for the use of PSC-derived respiratory epithelial cells in the study of cell-virus interactions. This report provides proof-of-principle experiments demonstrating, for the first time, that human respiratory progenitor cells derived from stem cells in the laboratory can be productively infected with human rhinovirus, the predominant cause of the common cold. ©AlphaMed Press.

Overall human mortality and morbidity due to exposure to air pollution.

PubMed

Samek, Lucyna

2016-01-01

Concentrations of particulate matter that contains particles with diameter ≤ 10 mm (PM10) and diameter ≤ 2.5 mm (PM2.5) as well as nitrogen dioxide (NO2) have considerable impact on human mortality, especially in the cases when cardiovascular or respiratory causes are attributed. Additionally, they affect morbidity. An estimation of human mortality and morbidity due to the increased concentrations of PM10, PM2.5 and NO2 between the years 2005-2013 was performed for the city of Kraków, Poland. For this purpose the Air Quality Health Impact Assessment Tool (AirQ) software was successfully applied. The Air Quality Health Impact Assessment Tool was used for the calculation of the total, cardiovascular and respiratory mortality as well as hospital admissions related to cardiovascular and respiratory diseases. Data on concentrations of PM10, PM2.5 and NO2, which was obtained from the website of the Voivodeship Inspectorate for Environmental Protection (WIOS) in Kraków, was used in this study. Total mortality due to exposure to PM10 in 2005 was found to be 41 deaths per 100 000 and dropped to 30 deaths per 100 000 in 2013. Cardiovascular mortality was 2 times lower than the total mortality. However, hospital admissions due to respiratory diseases were more than an order of magnitude higher than the respiratory mortality. The calculated total mortality due to PM2.5 was higher than that due to PM10. Air pollution was determined to have a significant effect on human health. The values obtained by the use of the AirQ software for the city of Kraków imply that exposure to polluted air can result in serious health problems. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Ocular Tropism of Respiratory Viruses

PubMed Central

Rota, Paul A.; Tumpey, Terrence M.

2013-01-01

SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

Using models in cardiovascular research: report on the satellite meeting to the International Congress of Physiological Sciences, Models in Cardiovascular Research.

PubMed

Doggrell, S A; Chan, V

2001-10-01

Humans have used animals for centuries to understand their own biology. From September 2-4, 2001, scientists from around the world converged on Brisbane, in Australia, to discuss the use of animal models in cardiovascular research at a satellite meeting to the 34th International Congress of Physiological Sciences (August 26-September 1, 2001, Christchurch, New Zealand). The appropriateness of each model to the human disease was a major consideration. Other themes were the use of models to understand pathological processes, and to determine potential new targets for pharmacological intervention.

Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

2001-01-01

Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

The Effect of a Smoking Ban on Hospitalization Rates for Cardiovascular and Respiratory Conditions in Prince Edward Island, Canada

PubMed Central

Gaudreau, Katherine; Sanford, Carolyn J.; Cheverie, Connie; McClure, Carol

2013-01-01

Background This is the first study to have examined the effect of smoking bans on hospitalizations in the Atlantic Canadian socio-economic, cultural and climatic context. On June 1, 2003 Prince Edward Island (PEI) enacted a province-wide smoking ban in public places and workplaces. Changes in hospital admission rates for cardiovascular (acute myocardial infarction, angina, and stroke) and respiratory (chronic obstructive pulmonary disease and asthma) conditions were examined before and after the smoking ban. Methods Crude annual and monthly admission rates for the above conditions were calculated from April 1, 1995 to December 31, 2008 in all PEI acute care hospitals. Autoregressive Integrated Moving Average time series models were used to test for changes in mean and trend of monthly admission rates for study conditions, control conditions and a control province after the comprehensive smoking ban. Age- and sex-based analyses were completed. Results The mean rate of acute myocardial infarctions was reduced by 5.92 cases per 100,000 person-months (P = 0.04) immediately after the smoking ban. The trend of monthly angina admissions in men was reduced by −0.44 cases per 100,000 person-months (P = 0.01) in the 67 months after the smoking ban. All other cardiovascular and respiratory admission changes were non-significant. Conclusions A comprehensive smoking ban in PEI reduced the overall mean number of acute myocardial infarction admissions and the trend of angina hospital admissions. PMID:23520450

The effect of a smoking ban on hospitalization rates for cardiovascular and respiratory conditions in Prince Edward Island, Canada.

PubMed

Gaudreau, Katherine; Sanford, Carolyn J; Cheverie, Connie; McClure, Carol

2013-01-01

This is the first study to have examined the effect of smoking bans on hospitalizations in the Atlantic Canadian socio-economic, cultural and climatic context. On June 1, 2003 Prince Edward Island (PEI) enacted a province-wide smoking ban in public places and workplaces. Changes in hospital admission rates for cardiovascular (acute myocardial infarction, angina, and stroke) and respiratory (chronic obstructive pulmonary disease and asthma) conditions were examined before and after the smoking ban. Crude annual and monthly admission rates for the above conditions were calculated from April 1, 1995 to December 31, 2008 in all PEI acute care hospitals. Autoregressive Integrated Moving Average time series models were used to test for changes in mean and trend of monthly admission rates for study conditions, control conditions and a control province after the comprehensive smoking ban. Age- and sex-based analyses were completed. The mean rate of acute myocardial infarctions was reduced by 5.92 cases per 100,000 person-months (P = 0.04) immediately after the smoking ban. The trend of monthly angina admissions in men was reduced by -0.44 cases per 100,000 person-months (P = 0.01) in the 67 months after the smoking ban. All other cardiovascular and respiratory admission changes were non-significant. A comprehensive smoking ban in PEI reduced the overall mean number of acute myocardial infarction admissions and the trend of angina hospital admissions.

Cardiovascular and fluid volume control in humans in space.

PubMed

Norsk, Peter

2005-08-01

The human cardiovascular system and regulation of fluid volume are heavily influenced by gravity. When decreasing the effects of gravity in humans such as by anti-orthostatic posture changes or immersion into water, venous return is increased by some 25%. This leads to central blood volume expansion, which is accompanied by an increase in renal excretion rates of water and sodium. The mechanisms for the changes in renal excretory rates include a complex interaction of cardiovascular reflexes, neuroendocrine variables, and physical factors. Weightlessness is unique to obtain more information on this complex interaction, because it is the only way to completely abolish the effects of gravity over longer periods. Results from space have been unexpected, because astronauts exhibit a fluid and sodium retaining state with activation of the sympathetic nervous system, which subjects during simulations by head-down bed rest do not. Therefore, the concept as to how weightlessness affects the cardiovascular system and modulates regulation of body fluids should be revised and new simulation models developed. Knowledge as to how gravity and weightlessness modulate integrated fluid volume control is of importance for understanding pathophysiology of heart failure, where gravity plays a strong role in fluid and sodium retention.

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

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

2008-01-01

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.

Stability of the human respiratory control system. I. Analysis of a two-dimensional delay state-space model.

PubMed

Batzel, J J; Tran, H T

2000-07-01

A number of mathematical models of the human respiratory control system have been developed since 1940 to study a wide range of features of this complex system. Among them, periodic breathing (including Cheyne-Stokes respiration and apneustic breathing) is a collection of regular but involuntary breathing patterns that have important medical implications. The hypothesis that periodic breathing is the result of delay in the feedback signals to the respiratory control system has been studied since the work of Grodins et al. in the early 1950's [12]. The purpose of this paper is to study the stability characteristics of a feedback control system of five differential equations with delays in both the state and control variables presented by Khoo et al. [17] in 1991 for modeling human respiration. The paper is divided in two parts. Part I studies a simplified mathematical model of two nonlinear state equations modeling arterial partial pressures of O2 and CO2 and a peripheral controller. Analysis was done on this model to illuminate the effect of delay on the stability. It shows that delay dependent stability is affected by the controller gain, compartmental volumes and the manner in which changes in the ventilation rate is produced (i.e., by deeper breathing or faster breathing). In addition, numerical simulations were performed to validate analytical results. Part II extends the model in Part I to include both peripheral and central controllers. This, however, necessitates the introduction of a third state equation modeling CO2 levels in the brain. In addition to analytical studies on delay dependent stability, it shows that the decreased cardiac output (and hence increased delay) resulting from the congestive heart condition can induce instability at certain control gain levels. These analytical results were also confirmed by numerical simulations.

Stability of the human respiratory control system. II. Analysis of a three-dimensional delay state-space model.

PubMed

Batzel, J J; Tran, H T

2000-07-01

A number of mathematical models of the human respiratory control system have been developed since 1940 to study a wide range of features of this complex system. Among them, periodic breathing (including Cheyne-Stokes respiration and apneustic breathing) is a collection of regular but involuntary breathing patterns that have important medical implications. The hypothesis that periodic breathing is the result of delay in the feedback signals to the respiratory control system has been studied since the work of Grodins et al. in the early 1950's [1]. The purpose of this paper is to study the stability characteristics of a feedback control system of five differential equations with delays in both the state and control variables presented by Khoo et al. [4] in 1991 for modeling human respiration. The paper is divided in two parts. Part I studies a simplified mathematical model of two nonlinear state equations modeling arterial partial pressures of O2 and CO2 and a peripheral controller. Analysis was done on this model to illuminate the effect of delay on the stability. It shows that delay dependent stability is affected by the controller gain, compartmental volumes and the manner in which changes in the ventilation rate is produced (i.e., by deeper breathing or faster breathing). In addition, numerical simulations were performed to validate analytical results. Part II extends the model in Part I to include both peripheral and central controllers. This, however, necessitates the introduction of a third state equation modeling CO2 levels in the brain. In addition to analytical studies on delay dependent stability, it shows that the decreased cardiac output (and hence increased delay) resulting from the congestive heart condition can induce instability at certain control gain levels. These analytical results were also confirmed by numerical simulations.

Dynamic interactions between musical, cardiovascular, and cerebral rhythms in humans.

PubMed

Bernardi, Luciano; Porta, Cesare; Casucci, Gaia; Balsamo, Rossella; Bernardi, Nicolò F; Fogari, Roberto; Sleight, Peter

2009-06-30

Reactions to music are considered subjective, but previous studies suggested that cardiorespiratory variables increase with faster tempo independent of individual preference. We tested whether compositions characterized by variable emphasis could produce parallel instantaneous cardiovascular/respiratory responses and whether these changes mirrored music profiles. Twenty-four young healthy subjects, 12 musicians (choristers) and 12 nonmusician control subjects, listened (in random order) to music with vocal (Puccini's "Turandot") or orchestral (Beethoven's 9th Symphony adagio) progressive crescendos, more uniform emphasis (Bach cantata), 10-second period (ie, similar to Mayer waves) rhythmic phrases (Giuseppe Verdi's arias "Va pensiero" and "Libiam nei lieti calici"), or silence while heart rate, respiration, blood pressures, middle cerebral artery flow velocity, and skin vasomotion were recorded.Common responses were recognized by averaging instantaneous cardiorespiratory responses regressed against changes in music profiles and by coherence analysis during rhythmic phrases. Vocal and orchestral crescendos produced significant (P=0.05 or better) correlations between cardiovascular or respiratory signals and music profile, particularly skin vasoconstriction and blood pressures, proportional to crescendo, in contrast to uniform emphasis, which induced skin vasodilation and reduction in blood pressures. Correlations were significant both in individual and group-averaged signals. Phrases at 10-second periods by Verdi entrained the cardiovascular autonomic variables. No qualitative differences in recorded measurements were seen between musicians and nonmusicians. Music emphasis and rhythmic phrases are tracked consistently by physiological variables. Autonomic responses are synchronized with music, which might therefore convey emotions through autonomic arousal during crescendos or rhythmic phrases.

Computational fluid dynamics modelling in cardiovascular medicine.

PubMed

Morris, Paul D; Narracott, Andrew; von Tengg-Kobligk, Hendrik; Silva Soto, Daniel Alejandro; Hsiao, Sarah; Lungu, Angela; Evans, Paul; Bressloff, Neil W; Lawford, Patricia V; Hose, D Rodney; Gunn, Julian P

2016-01-01

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges. Published by the BMJ Publishing Group Limited. For permission

A Comprehensive TALEN-Based Knockout Library for Generating Human Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases

PubMed Central

Karakikes, Ioannis; Termglinchan, Vittavat; Cepeda, Diana A.; Lee, Jaecheol; Diecke, Sebastian; Hendel, Ayal; Itzhaki, Ilanit; Ameen, Mohamed; Shrestha, Rajani; Wu, Haodi; Ma, Ning; Shao, Ning-Yi; Seeger, Timon; Woo, Nicole; Wilson, Kitchener D.; Matsa, Elena; Porteus, Matthew H.; Sebastiano, Vittorio; Wu, Joseph C.

2017-01-01

Rationale Targeted genetic engineering using programmable nucleases such as transcription activator–like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome. Objective The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases in vitro. Methods and Results By incorporating extensive literature and database searches, we designed a collection of TALEN constructs to knockout (KO) eighty-eight human genes that are associated with cardiomyopathies and congenital heart diseases. The TALEN pairs were designed to induce double-strand DNA break near the starting codon of each gene that either disrupted the start codon or introduced a frameshift mutation in the early coding region, ensuring faithful gene KO. We observed that all the constructs were active and disrupted the target locus at high frequencies. To illustrate the general utility of the TALEN-mediated KO technique, six individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out with high efficiency and specificity in human iPSCs. By selectively targeting a dilated cardiomyopathy (DCM)-causing mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes (iPSC-CMs), we demonstrated that the KO strategy ameliorates the DCM phenotype in vitro. In addition, we modeled the Holt-Oram syndrome (HOS) in iPSC-CMs in vitro and uncovered novel pathways regulated by TBX5 in human cardiac myocyte development. Conclusion Collectively, our study illustrates the powerful combination of iPSCs and genome editing technology for understanding the biological function of genes and the pathological significance of genetic variants in human cardiovascular diseases. The methods, strategies, constructs and iPSC lines developed in this study provide a validated, readily available resource for cardiovascular

A human lung xenograft mouse model of Nipah virus infection.

PubMed

Valbuena, Gustavo; Halliday, Hailey; Borisevich, Viktoriya; Goez, Yenny; Rockx, Barry

2014-04-01

Nipah virus (NiV) is a member of the genus Henipavirus (family Paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). NiV can cause Acute Lung Injury (ALI) in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7) TCID50/gram lung tissue) as early as 3 days post infection (pi). NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

Potential cardiovascular implications of Sea Buckthorn berry consumption in humans.

PubMed

Sayegh, Marietta; Miglio, Cristiana; Ray, Sumantra

2014-08-01

Diets rich in fruits and vegetables have been correlated with decreased risks of cardiovascular disease. Particularly, berry consumption has been associated with reductions in cardiovascular risk. Despite the range of potentially beneficial phytochemical components (vitamins, polyphenols, carotenoids, and fatty acids), there is little evidence underpinning the cardiovascular effects of sea buckthorn (SB) berries. The purpose of this review is to evaluate the benefits of SB consumption on cardiovascular health in human trials. Only six human studies were found, which examine the effect of SB berries on cardiovascular outcomes (i.e., lipid metabolism, platelet aggregation, and inflammation). Although there appears to be an inverse association between SB consumption and cardiovascular risk factors, the evidence is still scarce and the results are inconsistent. In addition, limitations in study design made it difficult to form firm conclusions. More "high-quality" human clinical trials are needed in order to establish the cardio-protective benefits of SB berries.

Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human

PubMed Central

Corley, Richard A.

2012-01-01

Computational fluid dynamics (CFD) models are useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. We improved the imaging and model development methods to the point where CFD models for the rat, monkey, and human now encompass airways from the nose or mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing 17±7, 19±9, or 9±2 airway generations were included in the rat, monkey and human models, respectively. A CFD/physiologically based pharmacokinetic model previously developed for acrolein was adapted for these anatomically correct extended airway models. Model parameters were obtained from the literature or measured directly. Airflow and acrolein uptake patterns were determined under steady-state inhalation conditions to provide direct comparisons with prior data and nasal-only simulations. Results confirmed that regional uptake was sensitive to airway geometry, airflow rates, acrolein concentrations, air:tissue partition coefficients, tissue thickness, and the maximum rate of metabolism. Nasal extraction efficiencies were predicted to be greatest in the rat, followed by the monkey, and then the human. For both nasal and oral breathing modes in humans, higher uptake rates were predicted for lower tracheobronchial tissues than either the rat or monkey. These extended airway models provide a unique foundation for comparing material transport and site-specific tissue uptake across a significantly greater range of conducting airways in the rat, monkey, and human than prior CFD models. PMID:22584687

Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep.

PubMed

Wang, Qiming; Gold, Nathan; Frasch, Martin G; Huang, Huaxiong; Thiriet, Marc; Wang, Xiaogang

2015-12-01

Fetal acidemia during labor is associated with an increased risk of brain injury and lasting neurological deficits. This is in part due to the repetitive occlusions of the umbilical cord (UCO) induced by uterine contractions. Whereas fetal heart rate (FHR) monitoring is widely used clinically, it fails to detect fetal acidemia. Hence, new approaches are needed for early detection of fetal acidemia during labor. We built a mathematical model of the UCO effects on FHR, mean arterial blood pressure (MABP), oxygenation and metabolism. Mimicking fetal experiments, our in silico model reproduces salient features of experimentally observed fetal cardiovascular and metabolic behavior including FHR overshoot, gradual MABP decrease and mixed metabolic and respiratory acidemia during UCO. Combined with statistical analysis, our model provides valuable insight into the labor-like fetal distress and guidance for refining FHR monitoring algorithms to improve detection of fetal acidemia and cardiovascular decompensation.

Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

PubMed

van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

2010-04-01

Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

Genetics of Human Cardiovascular Disease

PubMed Central

Kathiresan, Sekar; Srivastava, Deepak

2012-01-01

Cardiovascular disease encompasses a range of conditions extending from myocardial infarction to congenital heart disease most of which are heritable. Enormous effort has been invested in understanding the genes and specific DNA sequence variants responsible for this heritability. Here, we review the lessons learned for monogenic and common, complex forms of cardiovascular disease. We also discuss key challenges that remain for gene discovery and for moving from genomic localization to mechanistic insights with an emphasis on the impact of next generation sequencing and the use of pluripotent human cells to understand the mechanism by which genetic variation contributes to disease. PMID:22424232

Synchronisation and coupling analysis: applied cardiovascular physics in sleep medicine.

PubMed

Wessel, Niels; Riedl, Maik; Kramer, Jan; Muller, Andreas; Penzel, Thomas; Kurths, Jurgen

2013-01-01

Sleep is a physiological process with an internal program of a number of well defined sleep stages and intermediate wakefulness periods. The sleep stages modulate the autonomous nervous system and thereby the sleep stages are accompanied by different regulation regimes for the cardiovascular and respiratory system. The differences in regulation can be distinguished by new techniques of cardiovascular physics. The number of patients suffering from sleep disorders increases unproportionally with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop highly-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Methods of cardiovascular physics are used to analyze heart rate, blood pressure and respiration to detect changes of the autonomous nervous system in different diseases. Data driven modeling analysis, synchronization and coupling analysis and their applications to biosignals in healthy subjects and patients with different sleep disorders are presented. Newly derived methods of cardiovascular physics can help to find indicators for these health risks.

Extreme weather and air pollution effects on cardiovascular and respiratory hospital admissions in Cyprus.

PubMed

Tsangari, H; Paschalidou, A K; Kassomenos, A P; Vardoulakis, S; Heaviside, C; Georgiou, K E; Yamasaki, E N

2016-01-15

In many regions of the world, climatic change is associated with increased extreme temperatures, which can have severe effects on mortality and morbidity. In this study, we examine the effect of extreme weather on hospital admissions in Cyprus, for inland and coastal areas, through the use of synoptic weather classifications (air mass types). In addition, the effect of particulate air pollution (PM10) on morbidity is examined. Our results show that two air mass types, namely (a) warm, rainy days with increased levels of water vapour in the atmosphere and (b) cold, cloudy days with increased levels of precipitation, were associated with increased morbidity in the form of hospital admissions. This was true both for cardiovascular and respiratory conditions, for all age groups, but particularly for the elderly, aged over 65. Particulate air pollution was also associated with increased morbidity in Cyprus, where the effect was more pronounced for cardiovascular diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Cardiovascular, respiratory, electrolyte and acid-base balance during continuous dexmedetomidine infusion in anesthetized dogs.

PubMed

Congdon, Jonathan M; Marquez, Megan; Niyom, Sirirat; Boscan, Pedro

2013-09-01

To evaluate the cardiovascular, respiratory, electrolyte and acid-base effects of a continuous infusion of dexmedetomidine during propofol-isoflurane anesthesia following premedication with dexmedetomidine. Prospective experimental study. Five adult male Walker Hound dogs 1-2 years of age averaging 25.4 ± 3.6 kg. Dogs were sedated with dexmedetomidine 10 μg kg(-1) IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg(-1) ) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg(-1) IV was administered over 5 minutes followed by an infusion of 0.5 μg kg(-1)  hour(-1) . Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid-base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD. No statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute(-1) , 78 ± 18 beats minute(-1) and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute(-1) , 78 ± 14 beats minute(-1) and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO2 , PaCO2 , pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion. Dexmedetomidine infusion using a loading dose of 0.5 μg kg(-1) IV followed by a constant rate infusion of 0.5 μg kg(-1)  hour(-1) does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg(-1) , in propofol-isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2�

Zebrafish models of cardiovascular diseases and their applications in herbal medicine research.

PubMed

Seto, Sai-Wang; Kiat, Hosen; Lee, Simon M Y; Bensoussan, Alan; Sun, Yu-Ting; Hoi, Maggie P M; Chang, Dennis

2015-12-05

The zebrafish (Danio rerio) has recently become a powerful animal model for cardiovascular research and drug discovery due to its ease of maintenance, genetic manipulability and ability for high-throughput screening. Recent advances in imaging techniques and generation of transgenic zebrafish have greatly facilitated in vivo analysis of cellular events of cardiovascular development and pathogenesis. More importantly, recent studies have demonstrated the functional similarity of drug metabolism systems between zebrafish and humans, highlighting the clinical relevance of employing zebrafish in identifying lead compounds in Chinese herbal medicine with potential beneficial cardiovascular effects. This paper seeks to summarise the scope of zebrafish models employed in cardiovascular studies and the application of these research models in Chinese herbal medicine to date. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

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

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Lin, Y-H

2006-01-01

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.

Respiratory Mucosal Proteome Quantification in Human Influenza Infections.

PubMed

Marion, Tony; Elbahesh, Husni; Thomas, Paul G; DeVincenzo, John P; Webby, Richard; Schughart, Klaus

2016-01-01

Respiratory influenza virus infections represent a serious threat to human health. Underlying medical conditions and genetic make-up predispose some influenza patients to more severe forms of disease. To date, only a few studies have been performed in patients to correlate a selected group of cytokines and chemokines with influenza infection. Therefore, we evaluated the potential of a novel multiplex micro-proteomics technology, SOMAscan, to quantify proteins in the respiratory mucosa of influenza A and B infected individuals. The analysis included but was not limited to quantification of cytokines and chemokines detected in previous studies. SOMAscan quantified more than 1,000 secreted proteins in small nasal wash volumes from infected and healthy individuals. Our results illustrate the utility of micro-proteomic technology for analysis of proteins in small volumes of respiratory mucosal samples. Furthermore, when we compared nasal wash samples from influenza-infected patients with viral load ≥ 2(8) and increased IL-6 and CXCL10 to healthy controls, we identified 162 differentially-expressed proteins between the two groups. This number greatly exceeds the number of DEPs identified in previous studies in human influenza patients. Most of the identified proteins were associated with the host immune response to infection, and changes in protein levels of 151 of the DEPs were significantly correlated with viral load. Most important, SOMAscan identified differentially expressed proteins heretofore not associated with respiratory influenza infection in humans. Our study is the first report for the use of SOMAscan to screen nasal secretions. It establishes a precedent for micro-proteomic quantification of proteins that reflect ongoing response to respiratory infection.

Respiratory Mucosal Proteome Quantification in Human Influenza Infections

PubMed Central

Marion, Tony; Elbahesh, Husni; Thomas, Paul G.; DeVincenzo, John P.; Webby, Richard; Schughart, Klaus

2016-01-01

Respiratory influenza virus infections represent a serious threat to human health. Underlying medical conditions and genetic make-up predispose some influenza patients to more severe forms of disease. To date, only a few studies have been performed in patients to correlate a selected group of cytokines and chemokines with influenza infection. Therefore, we evaluated the potential of a novel multiplex micro-proteomics technology, SOMAscan, to quantify proteins in the respiratory mucosa of influenza A and B infected individuals. The analysis included but was not limited to quantification of cytokines and chemokines detected in previous studies. SOMAscan quantified more than 1,000 secreted proteins in small nasal wash volumes from infected and healthy individuals. Our results illustrate the utility of micro-proteomic technology for analysis of proteins in small volumes of respiratory mucosal samples. Furthermore, when we compared nasal wash samples from influenza-infected patients with viral load ≥ 28 and increased IL-6 and CXCL10 to healthy controls, we identified 162 differentially-expressed proteins between the two groups. This number greatly exceeds the number of DEPs identified in previous studies in human influenza patients. Most of the identified proteins were associated with the host immune response to infection, and changes in protein levels of 151 of the DEPs were significantly correlated with viral load. Most important, SOMAscan identified differentially expressed proteins heretofore not associated with respiratory influenza infection in humans. Our study is the first report for the use of SOMAscan to screen nasal secretions. It establishes a precedent for micro-proteomic quantification of proteins that reflect ongoing response to respiratory infection. PMID:27088501

Roadmap for cardiovascular circulation model

PubMed Central

Bradley, Christopher P.; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R.; Omholt, Stig W.; Chase, J. Geoffrey; Müller, Lucas O.; Watanabe, Sansuke M.; Blanco, Pablo J.; de Bono, Bernard; Hunter, Peter J.

2016-01-01

Abstract Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well‐established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo‐skeletal system. The computational infrastructure for the cardiovascular model should provide for near real‐time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model. PMID:27506597

Duration of daily TV/screen watching with cardiovascular, respiratory, mental and psychiatric health: Scottish Health Survey, 2012-2013.

PubMed

Shiue, Ivy

2015-01-01

The link of duration of TV and/or screen watching and chronic health conditions by subtypes is unclear. Therefore, the relationship between TV and/or screen watching hours and cardiovascular, respiratory, mental and psychiatric health and well-being (happiness) was assessed in an independent population-based survey to identify correlations of various hours with health conditions. Data was retrieved from the Scottish Health Survey, 2012-2013. Information on demographics, lifestyle factors, self-reported health conditions and TV and/or screen watching duration in both Scottish adults and children was collected by annual household interviews. Chi-square test and survey weighted logistic and multi-nominal modelling were performed. 5527 (57.0%) Scottish adults aged 16-99 watched TV and/or screen daily for 3 + h on average. There was a trend toward more hypertension, angina, stroke, diabetes, chronic obstructive pulmonary disease and poor self-rated health and mental health. Reporting watching TV and/or screen for 4 + h, for 5 + h and for 8 + h was associated with higher rates of heart attack, heart murmur or other heart troubles and abnormal heart rhythms, respectively. 414 (20.7%) Scottish children aged 4-12 watched TV and/or screen for 3h or more. They tended to have poor self-rated health and life difficulties perceived as emotional and behavioural problems. There were associations between various hours of TV and/or screen watching (3+h) and poor health observed both in Scottish adults and children. Future educational and public health programmes minimising TV and/or screen watching in order to protect cardiovascular, respiratory, mental and psychiatric health might be considered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.

PubMed

Russell, James C; Proctor, Spencer D

2006-01-01

Cardiovascular disease, the leading cause of death in much of the modern world, is the common symptomatic end stage of a number of distinct diseases and, therefore, is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on animal models that mimic human disease processes. The focus of this review is to identify suitable animal models and insights into cardiovascular disease achieved to date using such models. The ideal animal model of cardiovascular disease will mimic the human subject metabolically and pathophysiologically, will be large enough to permit physiological and metabolic studies, and will develop end-stage disease comparable to those in humans. Given the complex multifactorial nature of cardiovascular disease, no one species will be suitable for all studies. Potential larger animal models are problematic due to cost, ethical considerations, or poor pathophysiological comparability to humans. Rabbits require high-cholesterol diets to develop cardiovascular disease, and there are no rabbit models of metabolic syndrome. Spontaneous mutations in rats provide several complementary models of obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, one of which spontaneously develops cardiovascular disease and ischemic lesions. The mouse, like normal rats, is characteristically resistant to cardiovascular disease, although genetically altered strains respond to cholesterol feeding with atherosclerosis, but not with end-stage ischemic lesions. The most useful and valid species/strains for the study of cardiovascular disease appear to be small rodents, rats, and mice. This fragmented field would benefit from a consensus on well-characterized appropriate models for the study of different aspects of cardiovascular disease and a renewed emphasis on the biology of underlying diseases.

Optimization behavior of brainstem respiratory neurons. A cerebral neural network model.

PubMed

Poon, C S

1991-01-01

A recent model of respiratory control suggested that the steady-state respiratory responses to CO2 and exercise may be governed by an optimal control law in the brainstem respiratory neurons. It was not certain, however, whether such complex optimization behavior could be accomplished by a realistic biological neural network. To test this hypothesis, we developed a hybrid computer-neural model in which the dynamics of the lung, brain and other tissue compartments were simulated on a digital computer. Mimicking the "controller" was a human subject who pedalled on a bicycle with varying speed (analog of ventilatory output) with a view to minimize an analog signal of the total cost of breathing (chemical and mechanical) which was computed interactively and displayed on an oscilloscope. In this manner, the visuomotor cortex served as a proxy (homolog) of the brainstem respiratory neurons in the model. Results in 4 subjects showed a linear steady-state ventilatory CO2 response to arterial PCO2 during simulated CO2 inhalation and a nearly isocapnic steady-state response during simulated exercise. Thus, neural optimization is a plausible mechanism for respiratory control during exercise and can be achieved by a neural network with cognitive computational ability without the need for an exercise stimulus.

Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

PubMed Central

Valls-i-Soler, Adolfo; Encinas, Esther; Lukas, John C.; Vozmediano, Valvanera; Suárez, Elena

2014-01-01

Background Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225–300 min). Also plasma samples for quantification of fentanyl were drawn. Results A “reliable degree of sedation” was observed up to T = 210–240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions. PMID:24595018

Roadmap for cardiovascular circulation model.

PubMed

Safaei, Soroush; Bradley, Christopher P; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R; Omholt, Stig W; Chase, J Geoffrey; Müller, Lucas O; Watanabe, Sansuke M; Blanco, Pablo J; de Bono, Bernard; Hunter, Peter J

2016-12-01

Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well-established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo-skeletal system. The computational infrastructure for the cardiovascular model should provide for near real-time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Cardiovascular Fitness and Cognitive Spatial Learning in Rodents and in Humans.

PubMed

Barak, Boaz; Feldman, Noa; Okun, Eitan

2015-09-01

The association between cardiovascular fitness and cognitive functions in both animals and humans is intensely studied. Research in rodents shows that a higher cardiovascular fitness has beneficial effects on hippocampus-dependent spatial abilities, and the underlying mechanisms were largely teased out. Research into the impact of cardiovascular fitness on spatial learning in humans, however, is more limited, and involves mostly behavioral and imaging studies. Herein, we point out the state of the art in the field of spatial learning and cardiovascular fitness. The differences between the methodologies utilized to study spatial learning in humans and rodents are emphasized along with the neuronal basis of these tasks. Critical gaps in the study of spatial learning in the context of cardiovascular fitness between the two species are discussed. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

Inter-fraction variations in respiratory motion models

NASA Astrophysics Data System (ADS)

McClelland, J. R.; Hughes, S.; Modat, M.; Qureshi, A.; Ahmad, S.; Landau, D. B.; Ourselin, S.; Hawkes, D. J.

2011-01-01

Respiratory motion can vary dramatically between the planning stage and the different fractions of radiotherapy treatment. Motion predictions used when constructing the radiotherapy plan may be unsuitable for later fractions of treatment. This paper presents a methodology for constructing patient-specific respiratory motion models and uses these models to evaluate and analyse the inter-fraction variations in the respiratory motion. The internal respiratory motion is determined from the deformable registration of Cine CT data and related to a respiratory surrogate signal derived from 3D skin surface data. Three different models for relating the internal motion to the surrogate signal have been investigated in this work. Data were acquired from six lung cancer patients. Two full datasets were acquired for each patient, one before the course of radiotherapy treatment and one at the end (approximately 6 weeks later). Separate models were built for each dataset. All models could accurately predict the respiratory motion in the same dataset, but had large errors when predicting the motion in the other dataset. Analysis of the inter-fraction variations revealed that most variations were spatially varying base-line shifts, but changes to the anatomy and the motion trajectories were also observed.

Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies.

PubMed

Reis, Jordano Ferreira; Monteiro, Valter Vinicius Silva; de Souza Gomes, Rafaelli; do Carmo, Matheus Moraes; da Costa, Glauber Vilhena; Ribera, Paula Cardoso; Monteiro, Marta Chagas

2016-11-15

Cardiovascular diseases (CVD) are an important cause of death worldwide. Anthocyanins are a subgroup of flavonoids found in berries, flowers, fruits and leaves. In epidemiological and clinical studies, these polyphenols have been associated with improved cardiovascular risk profiles as well as decreased comorbidities. Human intervention studies using berries, vegetables, parts of plants and cereals (either fresh or as juice) or purified anthocyanin-rich extracts have demonstrated significant improvements in low density lipoproteins oxidation, lipid peroxidation, total plasma antioxidant capacity, and dyslipidemia as well as reduced levels of CVD molecular biomarkers. This review discusses the use of anthocyanins in animal models and their applications in human medicine, as dietary supplements or as new potent drugs against cardiovascular disease.

Mathematical modelling of a human external respiratory system

NASA Technical Reports Server (NTRS)

1977-01-01

A closed system of algebraic and common differential equations solved by computer is investigated. It includes equations which describe the activity pattern of the respiratory center, the phrenic nerve, the thrust produced by the diaphragm as a function of the lung volume and discharge frequency of the phrenic nerve, as well as certain relations of the lung stretch receptors and chemoreceptors on various lung and blood characteristics, equations for lung biomechanics, pulmonary blood flow, alveolar gas exchange and capillary blood composition equations to determine various air and blood flow and gas exchange parameters, and various gas mixing and arterial and venous blood composition equations, to determine other blood, air and gas mixing characteristics. Data are presented by means of graphs and tables, and some advantages of this model over others are demonstrated by test results.

Cardiovascular, electrodermal, and respiratory response patterns to fear- and sadness-inducing films.

PubMed

Kreibig, Sylvia D; Wilhelm, Frank H; Roth, Walton T; Gross, James J

2007-09-01

Responses to fear- and sadness-inducing films were assessed using a broad range of cardiovascular (heart rate, T-wave amplitude, low- and high-frequency heart rate variability, stroke volume, preejection period, left-ventricular ejection time, Heather index, blood pressure, pulse amplitude and transit time, and finger temperature), electrodermal (level, response rate, and response amplitude), and respiratory (rate, tidal volume and its variability, inspiratory flow rate, duty cycle, and end-tidal pCO(2)) measures. Subjective emotional experience and facial behavior (Corrugator Supercilii and Zygomaticus Major EMG) served as control measures. Results indicated robust differential physiological response patterns for fear, sadness, and neutral (mean classification accuracy 85%). Findings are discussed in terms of the fight-flight and conservation-withdrawal responses and possible limitations of a valence-arousal categorization of emotion in affective space.

Analysis of cardiovascular regulation.

PubMed

Wilhelm, F H; Grossman, P; Roth, W T

1999-01-01

Adequate characterization of hemodynamic and autonomic responses to physical and mental stress can elucidate underlying mechanisms of cardiovascular disease or anxiety disorders. We developed a physiological signal processing system for analysis of continuously recorded ECG, arterial blood pressure (BP), and respiratory signals using the programming language Matlab. Data collection devices are a 16-channel digital, physiological recorder (Vitaport), a finger arterial pressure transducer (Finapres), and a respiratory inductance plethysmograph (Respitrace). Besides the conventional analysis of the physiological channels, power spectral density and transfer functions of respiration, heart rate, and blood pressure variability are used to characterize respiratory sinus arrhythmia (RSA), 0.10-Hz BP oscillatory activity (Mayer-waves), and baroreflex sensitivity. The arterial pressure transducer waveforms permit noninvasive estimation of stroke volume, cardiac output, and systemic vascular resistance. Time trends in spectral composition of indices are assessed using complex demodulation. Transient dynamic changes of cardiovascular parameters at the onset of stress and recovery periods are quantified using a regression breakpoint model that optimizes piecewise linear curve fitting. Approximate entropy (ApEn) is computed to quantify the degree of chaos in heartbeat dynamics. Using our signal processing system we found distinct response patterns in subgroups of patients with coronary artery disease or anxiety disorders, which were related to specific pharmacological and behavioral factors.

Extreme respiratory sinus arrhythmia enables overwintering black bear survival--physiological insights and applications to human medicine.

PubMed

Laske, Timothy G; Harlow, Henry J; Garshelis, David L; Iaizzo, Paul A

2010-10-01

American black bears survive winter months without food and water while in a mildly hypothermic, hypometabolic, and inactive state, yet they appear to be able to return to near-normal systemic function within minutes of arousal. This study's goal was to characterize the cardiovascular performance of overwintering black bears and elicit the underlying mechanisms enabling survival. Mid-winter cardiac electrophysiology was assessed in four wild black bears using implanted data recorders. Paired data from early and late winter were collected from 37 wild bears, which were anesthetized and temporarily removed from their dens to record cardiac electrophysiological parameters (12-lead electrocardiograms) and cardiac dimensional changes (echocardiography). Left ventricular thickness, primary cardiac electrophysiological parameters, and cardiovascular response to threats ("fight or flight" response) were preserved throughout winter. Dramatic respiratory sinus arrhythmias were recorded (cardiac cycle length variations up to 865%) with long sinus pauses between breaths (up to 13 s). The accelerated heart rate during breathing efficiently transports oxygen, with the heart "resting" between breaths to minimize energy usage. This adaptive cardiac physiology may have broad implications for human medicine.

Studies of the effects of gravitational and inertial forces on cardiovascular and respiratory dynamics

NASA Technical Reports Server (NTRS)

Ritman, E. L.; Wood, E. H.

1973-01-01

The current status and application are described of the biplane video roentgen densitometry, videometry and video digitization systems. These techniques were developed, and continue to be developed for studies of the effects of gravitational and inertial forces on cardiovascular and respiratory dynamics in intact animals and man. Progress is reported in the field of lung dynamics and three-dimensional reconstruction of the dynamic thoracic contents from roentgen video images. It is anticipated that these data will provide added insight into the role of shape and internal spatial relationships (which is altered particularly by acceleration and position of the body) of these organs as an indication of their functional status.

Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild Chimpanzees, Uganda, 2013.

PubMed

Scully, Erik J; Basnet, Sarmi; Wrangham, Richard W; Muller, Martin N; Otali, Emily; Hyeroba, David; Grindle, Kristine A; Pappas, Tressa E; Thompson, Melissa Emery; Machanda, Zarin; Watters, Kelly E; Palmenberg, Ann C; Gern, James E; Goldberg, Tony L

2018-02-01

We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in 2013 for which molecular and epidemiologic analyses implicate human rhinovirus C as the cause. Postmortem samples from an infant chimpanzee yielded near-complete genome sequences throughout the respiratory tract; other pathogens were absent. Epidemiologic modeling estimated the basic reproductive number (R 0 ) for the epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3 CDHR3-Y 529 allele, which increases risk for rhinovirus C infection and asthma in human children. These results indicate that chimpanzees exhibit a species-wide genetic susceptibility to rhinovirus C and that this virus, heretofore considered a uniquely human pathogen, can cross primate species barriers and threatens wild apes. We advocate engineering interventions and prevention strategies for rhinovirus infections for both humans and wild apes.

Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.

PubMed

Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

2018-05-01

Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P < 0.001). The viral mean load was 4.81 ± 1.98 log10 copies/1000 cells for patients under the age of 4-year-old (P < 0.001). The viral mean loads were 4.51 ± 2.04 cells in patients with low respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.

Ecological Study on Hospitalizations for Cancer, Cardiovascular, and Respiratory Diseases in the Industrial Area of Etang-de-Berre in the South of France

PubMed Central

Pascal, Laurence; Stempfelet, Morgane; Declercq, Christophe

2013-01-01

The Etang-de-Berre area is a large industrialized area in the South of France, exposing 300,000 inhabitants to the plumes of its industries. The possible associated health risks are of the highest concern to the population, who asked for studies investigating their health status. A geographical ecological study based on standardized hospitalizations ratios for cancer, cardiovascular, and respiratory diseases was carried out over the 2004–2007 period. Exposure to air pollution was assessed using dispersion models coupled with a geographic information system to estimate an annual mean concentration of sulfur dioxide (SO2) for each district. Results showed an excess risk of hospitalization for myocardial infarction in women living in districts with medium or high SO2 exposure, respectively, 38% [CI 95% 4 : 83] and 54% [14 : 110] greater than women living in districts at the reference level exposure. A 26% [2 : 57] excess risk of hospitalization for myocardial infarction was also observed in men living in districts with high SO2 levels. No excess risk of hospitalization for respiratory diseases or for cancer was observed, except for acute leukemia in men only. Results illustrate the impact of industrial air pollution on the cardiovascular system and call for an improvement of the air quality in the area. PMID:23864868

Inhaled particle deposition in unsteady-state respiratory flow at a numerically constructed model of the human larynx.

PubMed

Takano, Hiroshi; Nishida, Naohiro; Itoh, Masayuki; Hyo, Noboru; Majima, Yuichi

2006-01-01

To evaluate the clinical effectiveness of aerosol therapy for the lower and upper respiratory airways, particle deposition at the human laryngeal region has been analyzed with various unsteady-state respiratory flow-patterns. The flow profiles and trajectory of aerosol particles were calculated by 3-D thermo-fluid analysis of a finite volume method (FVM) with 8-CPUs parallel computational system. A reconstructed physical model of the real laryngeal airways was modified from 3-D CAM modeling function of Rhinoceros based on the images of Magnetic Resonance Imaging (MRI). By using 104 MRI images taken vertically and horizontally at intervals of 2 mm on the oral cavity and the pharynx-larynx respectively, 3-D physical model of the laryngeal airways was obtained. The numerical results of flow profile analyzed by the unsteady-state respiration model showed that vortex flow was occurred with time at near larynx, showing uniform flow profile in both the oral cavity and upper side of pharynx. The vortex was appeared at the anterior part of the epiglottis and downward of the vocal cord. However, it was confirmed that few particles deposit in the vocal cord. In these cases, the particle deposition was taken place mostly at the oral cavity and the oropharynx. On the other hand, the relationship between the particle deposition efficiency and the impaction in the laryngeal region was well agreement with the data sets of ICRP task group (1993) for the larynx deposition.

Clinical models of cardiovascular regulation after weightlessness

NASA Technical Reports Server (NTRS)

Robertson, D.; Jacob, G.; Ertl, A.; Shannon, J.; Mosqueda-Garcia, R.; Robertson, R. M.; Biaggioni, I.

1996-01-01

After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

[Cardiovascular manifestations of human toxocariasis].

PubMed

Bolívar-Mejía, Adrián; Rodríguez-Morales, Alfonso J; Paniz-Mondolfi, Alberto E; Delgado, Olinda

2013-01-01

Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxocariasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Effects of hypothyroidism on the respiratory system and control of breathing: Human studies and animal models.

PubMed

Schlenker, Evelyn H

2012-04-30

Hypothyroidism, subclinical hypothyroidism and euthyroid sick syndrome, are prevalent disorders that affect all body systems including the respiratory system and control of breathing. The purpose of this review article is to discuss the regulation of thyroid hormone production and their function at the cellular level; the many causes of hypothyroidism; the effects of hypothyroidism on the respiratory system and on control of ventilation in hypothyroid patients; the variety of ways animal models of hypothyroidism are induced; and how in animal models hypothyroidism affects the respiratory system and control of breathing including neurotransmitters that influence breathing. Finally, this review will present controversies that exist in the field and thus encourage new research directions. Because of the high prevalence of hypothyroidism and subclinical forms of hypothyroidism and their influence on ventilation and the respiratory system, understanding underlying molecular mechanisms is necessary to ascertain how and sometimes why not thyroid replacement may normalize function. Copyright © 2012 Elsevier B.V. All rights reserved.

A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

PubMed

Cockrell, Adam S; Yount, Boyd L; Scobey, Trevor; Jensen, Kara; Douglas, Madeline; Beall, Anne; Tang, Xian-Chun; Marasco, Wayne A; Heise, Mark T; Baric, Ralph S

2016-11-28

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

PubMed

Judge, Eoin P; Hughes, J M Lynne; Egan, Jim J; Maguire, Michael; Molloy, Emer L; O'Dea, Shirley

2014-09-01

The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.

Development of a Sampler for Total Aerosol Deposition in the Human Respiratory Tract

PubMed Central

Koehler, Kirsten A.; Clark, Phillip; Volckens, John

2009-01-01

Studies that seek to associate reduced human health with exposure to occupational and environmental aerosols are often hampered by limitations in the exposure assessment process. One limitation involves the measured exposure metric itself. Current methods for personal exposure assessment are designed to estimate the aspiration of aerosol into the human body. Since a large proportion of inhaled aerosol is subsequently exhaled, a portion of the aspirated aerosol will not contribute to the dose. This leads to variable exposure misclassification (for heterogenous exposures) and increased uncertainty in health effect associations. Alternatively, a metric for respiratory deposition would provide a more physiologically relevant estimate of risk. To address this challenge, we have developed a method to estimate the deposition of aerosol in the human respiratory tract using a sampler engineered from polyurethane foam. Using a semi-empirical model based on inertial, gravitational, and diffusional particle deposition, a foam was engineered to mimic aerosol total deposition in the human respiratory tract. The sampler is comprised of commercially available foam with fiber diameter = 49.5 μm (equivalent to industry standard 100 PPI foam) of 8 cm thickness operating at a face velocity of 1.3 m s−1. Additionally, the foam sampler yields a relatively low-pressure drop, independent of aerosol loading, providing uniform particle collection efficiency over time. PMID:19638392

Chronic stress impacts the cardiovascular system: animal models and clinical outcomes.

PubMed

Golbidi, Saeid; Frisbee, Jefferson C; Laher, Ismail

2015-06-15

Psychological stresses are associated with cardiovascular diseases to the extent that cardiovascular diseases are among the most important group of psychosomatic diseases. The longstanding association between stress and cardiovascular disease exists despite a large ambiguity about the underlying mechanisms. An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies. Copyright © 2015 the American Physiological Society.

A 10-year time-series analysis of respiratory and cardiovascular morbidity in Nicosia, Cyprus: the effect of short-term changes in air pollution and dust storms

PubMed Central

Middleton, Nicos; Yiallouros, Panayiotis; Kleanthous, Savvas; Kolokotroni, Ourania; Schwartz, Joel; Dockery, Douglas W; Demokritou, Phil; Koutrakis, Petros

2008-01-01

Background To date, a substantial body of research has shown adverse health effects of short-term changes in levels of air pollution. Such associations have not been investigated in smaller size cities in the Eastern Mediterranean. A particular feature in the region is dust blown from the Sahara a few times a year resulting in extreme PM10 concentrations. It is not entirely clear whether such natural phenomena pose the same risks. Methods The effect of changes in daily levels of particulate matter (PM10) and ozone (O3) on hospitalization for all, cardiovascular and respiratory causes in the two hospitals in Nicosia during 1 January 1995 and 30 December 2004 was investigated using generalized additive Poisson models after controlling for long- and short-term patterns as well as for the effect of weather. Meteorological records were reviewed to identify dust-storm days and analyses were repeated to quantify their effect on cardio-respiratory morbidity. Results For every 10 μg/m3 increase in daily average PM10 concentrations, there was a 0.9% (95%CI: 0.6%, 1.2%) increase in all-cause and 1.2% (95%CI: -0.0%, 2.4%) increase in cardiovascular admissions. With respect to respiratory causes, an effect was observed only in the warm months. No lagged effects with levels of PM10 were observed. In contrast, positive associations with levels of ozone were only observed the two days prior to admission. These appeared stronger for cardiovascular causes and independent of the effect of PM. All-cause and cardiovascular admissions were 4.8% (95%CI: 0.7%, 9.0%) and 10.4% (95%CI: -4.7%, 27.9%) higher on dust storm days respectively. In both cases the magnitude of effect was comparable to that seen on the quartile of non-storm days with the highest levels of PM10. Conclusion We observed an increased risk of hospitalization at elevated levels of particulate matter and ozone generally consistent with the magnitude seen across several European cities. We also observed an increased risk

Simultaneous influenza and respiratory syncytial virus infection in human respiratory tract

NASA Astrophysics Data System (ADS)

Pinky, Lubna Jahan Rashid; Dobrovolny, Hana

2015-03-01

Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is not uncommon in hospitalized patients, although it is not clear whether these infections are more or less severe than single infections. We use mathematical models to study the dynamics of simultaneous influenza (flu) and respiratory syncytial virus (RSV) infection, two of the more common respiratory viruses, in an effort to understand simultaneous infections. We examine the roles of initial viral inoculum, relative starting time, and cell regeneration on the severity of the infection. We also study the effect of antiviral treatment on the course of the infection. This study shows that, unless treated with antivirals, flu always takes over the infection no matter how small the initial dose and how delayed it starts with respect to RSV.

[The influence of music on the effectiveness of therapeutic physical exercises in patients with cardiovascular and respiratory pathologies].

PubMed

Dzhuraeva, L A; Sadykova, Kh A; Maslova, G V

1989-01-01

Medical and pedagogical observation performed during hours of therapeutic exercise in groups of cardiovascular and respiratory diseases patients proved a beneficial effect of music accompaniment. This was most efficient when started from the very onset of the exercise course for the former group of patients and from the second week of the exercise course for the latter patients. It is stated that music should be used differentially at different stages of hospital conditioning.

Proximity to coke works and hospital admissions for respiratory and cardiovascular disease in England and Wales

PubMed Central

Aylin, P; Bottle, A; Wakefield, J; Jarup, L; Elliott, P

2001-01-01

BACKGROUND—The incidence of hospital admissions for respiratory and cardiovascular diseases in areas close to operating coke works in England and Wales was investigated.
METHODS—A small area study using distance from source as a proxy for exposure was undertaken in subjects aged 65 or over and children under 5 years within 7.5 km of four coke works (1991 estimated populations 87 760 and 43 932, respectively). The main outcome measures were emergency hospital admissions in 1992/3-1994/5 with a primary diagnosis of coronary heart disease (ICD 410-414), stroke (ICD 431-438), all respiratory diseases (ICD 460-519), chronic obstructive pulmonary disease (ICD 491-492), and asthma (ICD 493) in those aged 65 or over, and all respiratory and asthma admissions in children under 5 years of age.
RESULTS—At age 65 or over the combined estimate of relative risk with proximity to coke works (per km) ranged from 0.99 (95% CI 0.90to 1.09) for chronic obstructive pulmonary disease to 1.03 (95% CI 0.94 to 1.13) for asthma. For children under 5 years the combined estimate of risk was 1.08 (95% CI 0.98 to 1.20) for all respiratory disease and 1.07 (95% CI 0.98 to 1.18) for asthma. There was evidence of significant heterogeneity in risk estimates between coke work groups, especially in children under 5 years (p<0.001 and p=0.004 for respiratory disease and asthma, respectively). For the Teesside coke works in North East England the relative risk with proximity (per km) was 1.09 (95% CI 1.06 to 1.12) for respiratory disease and 1.09 (95% CI 1.04 to 1.15) for asthma.
CONCLUSIONS—No evidence overall was found for an association between hospital admissions and living near operational coke works in England and Wales. Trends of a higher risk of hospital admission for respiratory disease and asthma among children with proximity to the Teesside plant require further investigation.

 PMID:11182017

Proximity to coke works and hospital admissions for respiratory and cardiovascular disease in England and Wales.

PubMed

Aylin, P; Bottle, A; Wakefield, J; Jarup, L; Elliott, P

2001-03-01

The incidence of hospital admissions for respiratory and cardiovascular diseases in areas close to operating coke works in England and Wales was investigated. A small area study using distance from source as a proxy for exposure was undertaken in subjects aged 65 or over and children under 5 years within 7.5 km of four coke works (1991 estimated populations 87 760 and 43 932, respectively). The main outcome measures were emergency hospital admissions in 1992/3-1994/5 with a primary diagnosis of coronary heart disease (ICD 410-414), stroke (ICD 431-438), all respiratory diseases (ICD 460-519), chronic obstructive pulmonary disease (ICD 491-492), and asthma (ICD 493) in those aged 65 or over, and all respiratory and asthma admissions in children under 5 years of age. At age 65 or over the combined estimate of relative risk with proximity to coke works (per km) ranged from 0.99 (95% CI 0.90 to 1.09) for chronic obstructive pulmonary disease to 1.03 (95% CI 0.94 to 1.13) for asthma. For children under 5 years the combined estimate of risk was 1.08 (95% CI 0.98 to 1.20) for all respiratory disease and 1.07 (95% CI 0.98 to 1.18) for asthma. There was evidence of significant heterogeneity in risk estimates between coke work groups, especially in children under 5 years (p<0.001 and p=0.004 for respiratory disease and asthma, respectively). For the Teesside coke works in North East England the relative risk with proximity (per km) was 1.09 (95% CI 1.06 to 1.12) for respiratory disease and 1.09 (95% CI 1.04 to 1.15) for asthma. No evidence overall was found for an association between hospital admissions and living near operational coke works in England and Wales. Trends of a higher risk of hospital admission for respiratory disease and asthma among children with proximity to the Teesside plant require further investigation.

A mathematical model of transport and regional uptake of radioactive gases in the human respiratory system

NASA Astrophysics Data System (ADS)

Baek, Inseok

The purpose of this research is to describe the development of a mathematical model of diffusion, convection, and lateral transport into the airway wall and alveolar absorption for inhaled radioactive gases in the human conductive and respiratory airways based on a Single Path Trumpet-bell model (SPM). Mathematical simulation models have been used successfully to study transport, absorption into the blood through alveoli, and lung tissue uptake of soluble and nonreactive radioactive gases. Results from such simulations also show clearly that inhaled radioactive gases are absorbed into the lung tissues as well as into the blood through the alveoli. In contrast to previous reports in the literature, the present study found that blood uptake through alveoli is much greater than that calculated previously. Regional depositions in the lung from inhaled radioactive gases are presented as the result of this simulation. The committed effective dose to lung tissue due to submersion in radioactive clouds has been newly defined using the results of this simulation.

Computer simulation of the human respiratory system for educational purposes.

PubMed

Botsis, Taxiarhis; Halkiotis, Stelios-Chris; Kourlaba, Georgia

2004-01-01

The main objective of this study was the development of a computer simulation system for the human respiratory system, in order to educate students of nursing. This approach was based on existing mathematical models and on our own constructed specific functions. For the development of this educational tool the appropriate software packages were used according to the special demands of this process. This system is called ReSim (Respiratory Simulation) and consists of two parts: the first part deals with pulmonary volumes and the second one represents the mechanical behavior of lungs. The target group evaluated ReSim. The outcomes of the evaluation process were positive and helped us realize the system characteristics that needed improvements. Our basic conclusion is that the extended use of such systems supports the educational process and offers new potential for learning.

Air pollution and hospital emergency room and admissions for cardiovascular and respiratory diseases in Doña Ana County, New Mexico.

PubMed

Rodopoulou, Sophia; Chalbot, Marie-Cecile; Samoli, Evangelia; Dubois, David W; San Filippo, Bruce D; Kavouras, Ilias G

2014-02-01

Doña Ana County in New Mexico regularly experiences severe air pollution episodes associated with windblown dust and fires. Residents of Hispanic/Latino origin constitute the largest population group in the region. We investigated the associations of ambient particulate matter and ozone with hospital emergency room and admissions for respiratory and cardiovascular visits in adults. We used trajectories regression analysis to determine the local and regional components of particle mass and ozone. We applied Poisson generalized models to analyze hospital emergency room visits and admissions adjusted for pollutant levels, humidity, temperature and temporal and seasonal effects. We found that the sources within 500km of the study area accounted for most of particle mass and ozone concentrations. Sources in Southeast Texas, Baja California and Southwest US were the most important regional contributors. Increases of cardiovascular emergency room visits were estimated for PM10 (3.1% (95% CI: -0.5 to 6.8)) and PM10-2.5 (2.8% (95% CI: -0.2 to 5.9)) for all adults during the warm period (April-September). When high PM10 (>150μg/m(3)) mass concentrations were excluded, strong effects for respiratory emergency room visits for both PM10 (3.2% (95% CI: 0.5-6.0)) and PM2.5 (5.2% (95% CI: -0.5 to 11.3)) were computed. Our analysis indicated effects of PM10, PM2.5 and O3 on emergency room visits during the April-September period in a region impacted by windblown dust and wildfires. Copyright © 2013 Elsevier Inc. All rights reserved.

Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract.

PubMed

Asgharian, B; Price, O T; Oldham, M; Chen, Lung-Chi; Saunders, E L; Gordon, T; Mikheev, V B; Minard, K R; Teeguarden, J G

2014-12-01

Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.

Global Considerations in Human Immunodeficiency Virus-Associated Respiratory Disease.

PubMed

Rylance, Jamie; Meghji, Jamilah; Miller, Robert F; Ferrand, Rashida A

2016-04-01

Respiratory tract infection, particularly tuberculosis, is a major cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Antiretroviral therapy (ART) has resulted in a dramatic increase in survival, although coverage of HIV treatment remains low in many parts of the world. There is a concurrent growing burden of chronic noninfectious respiratory disease as a result of increased survival. Many risk factors associated with the development of respiratory disease, such as cigarette smoking and intravenous drug use, are overrepresented among people living with HIV. In addition, there is emerging evidence that HIV infection may directly cause or accelerate the course of chronic lung disease. This review summarizes the clinical spectrum and epidemiology of respiratory tract infections and noninfectious pulmonary pathologies, and factors that explain the global variation in HIV-associated respiratory disease. The potential for enhancing diagnoses of noninfective chronic conditions through the use of clinical algorithms is discussed. We also consider issues in assessment and management of HIV-related respiratory disease in view of the increasing global scale up of ART. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cardiovascular, cerebrovascular, and respiratory changes induced by different types of music in musicians and non-musicians: the importance of silence.

PubMed

Bernardi, L; Porta, C; Sleight, P

2006-04-01

To assess the potential clinical use, particularly in modulating stress, of changes in the cardiovascular and respiratory systems induced by music, specifically tempo, rhythm, melodic structure, pause, individual preference, habituation, order effect of presentation, and previous musical training. Measurement of cardiovascular and respiratory variables while patients listened to music. University research laboratory for the study of cardiorespiratory autonomic function. 12 practising musicians and 12 age matched controls. After a five minute baseline, presentation in random order of six different music styles (first for a two minute, then for a four minute track), with a randomly inserted two minute pause, in either sequence. Breathing rate, ventilation, carbon dioxide, RR interval, blood pressure, mid-cerebral artery flow velocity, and baroreflex. Ventilation, blood pressure, and heart rate increased and mid-cerebral artery flow velocity and baroreflex decreased with faster tempi and simpler rhythmic structures compared with baseline. No habituation effect was seen. The pause reduced heart rate, blood pressure, and minute ventilation, even below baseline. An order effect independent of style was evident for mid-cerebral artery flow velocity, indicating a progressive reduction with exposure to music, independent of style. Musicians had greater respiratory sensitivity to the music tempo than did non-musicians. Music induces an arousal effect, predominantly related to the tempo. Slow or meditative music can induce a relaxing effect; relaxation is particularly evident during a pause. Music, especially in trained subjects, may first concentrate attention during faster rhythms, then induce relaxation during pauses or slower rhythms.

Reductions in cardiovascular, cerebrovascular, and respiratory mortality following the national irish smoking ban: interrupted time-series analysis.

PubMed

Stallings-Smith, Sericea; Zeka, Ariana; Goodman, Pat; Kabir, Zubair; Clancy, Luke

2013-01-01

Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality. A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence. Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76-0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63-0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54-0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46-0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35-64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32-0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305-4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking. The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular causes, and is the first to demonstrate reductions in

Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms

NASA Technical Reports Server (NTRS)

Gonschorek, A. S.; Lu, L. L.; Halliwill, J. R.; Beightol, L. A.; Taylor, J. A.; Painter, J. A.; Warzel, H.; Eckberg, D. L.

2001-01-01

Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.

Impact of improved air quality during the 1996 Summer Olympic Games in Atlanta on multiple cardiovascular and respiratory outcomes.

PubMed

Peel, Jennifer L; Klein, Mitchell; Flanders, W Dana; Mulholland, James A; Tolbert, Paige E

2010-04-01

Substantial evidence supports an association between ambient air pollution, especially particulate matter (PM*) and ozone (O3), and acute cardiovascular and respiratory morbidity. There is increasing interest in accountability research to evaluate whether actions taken to reduce air pollution will result in reduced morbidity. This study capitalized on a unique opportunity to evaluate the impact of a local, short-term intervention effort to reduce traffic in Atlanta during the 1996 Summer Olympic Games (July 19-August 4). Air pollutant concentrations both inside and outside of Atlanta were examined during the Olympic period and surrounding periods. Emergency department (ED) visits were examined to evaluate changes in usage patterns. ED visits for respiratory and cardiovascular conditions were examined in relation to the Olympic period using Poisson time-series analysis with adjustment for time trends and meteorologic conditions. O3 concentrations were approximately 30% lower during the Olympic Games compared with the four weeks before and after the Olympic Games (baseline periods); however, we observed similar reductions in O3 concentrations in several other cities in the Southeastern United States. We observed little or no evidence of reduced ED visits during the Olympic Games; the estimates were sensitive to choice of analytic model and to method of adjusting for temporal trends. The meteorologic conditions during the Olympic Games, along with the reductions in O3 observed in various cities not impacted by the Olympic Games, suggest that both meteorologic conditions-and reduced traffic may have played a role in the observed reduction in O3 concentration in Atlanta. Additionally, it is likely that this particular intervention strategy would not be sustainable as a pollution-reduction strategy. This study demonstrates some limitations of conducting retrospective accountability research.

Cardiovascular services and human resources in Puerto Rico - 2008.

PubMed

García-Palmieri, Mario R

2009-01-01

Available information (2004-2008) concerning population statistics, the occurrence of cardiovascular disease, cardiovascular services and human resources in Puerto Rico is presented. Relevant information concerning life expectancy at birth, death by specific causes in a recent four years period, the commonest causes of death, and the related cardiovascular risk factors prevalence data available is included. The surgical and medical interventional services rendered to cardiovascular patients in different institutions and their locations in Puerto Rico in the year 2008 is presented. Some remarks concerning the productivity of physicians by our Schools of Medicine is included. Information about ACGME accredited postgraduate cardiovascular training programs conducted in Puerto Rico is presented. Data concerning the prevalence of hypertension, diabetes mellitus, overweight and obesity obtained by BRFSS in presented.

Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

PubMed

Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

2018-06-01

The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Reference respiratory waveforms by minimum jerk model analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anetai, Yusuke, E-mail: anetai@radonc.med.osaka-u.ac.jp; Sumida, Iori; Takahashi, Yutaka

Purpose: CyberKnife{sup ®} robotic surgery system has the ability to deliver radiation to a tumor subject to respiratory movements using Synchrony{sup ®} mode with less than 2 mm tracking accuracy. However, rapid and rough motion tracking causes mechanical tracking errors and puts mechanical stress on the robotic joint, leading to unexpected radiation delivery errors. During clinical treatment, patient respiratory motions are much more complicated, suggesting the need for patient-specific modeling of respiratory motion. The purpose of this study was to propose a novel method that provides a reference respiratory wave to enable smooth tracking for each patient. Methods: The minimummore » jerk model, which mathematically derives smoothness by means of jerk, or the third derivative of position and the derivative of acceleration with respect to time that is proportional to the time rate of force changed was introduced to model a patient-specific respiratory motion wave to provide smooth motion tracking using CyberKnife{sup ®}. To verify that patient-specific minimum jerk respiratory waves were being tracked smoothly by Synchrony{sup ®} mode, a tracking laser projection from CyberKnife{sup ®} was optically analyzed every 0.1 s using a webcam and a calibrated grid on a motion phantom whose motion was in accordance with three pattern waves (cosine, typical free-breathing, and minimum jerk theoretical wave models) for the clinically relevant superior–inferior directions from six volunteers assessed on the same node of the same isocentric plan. Results: Tracking discrepancy from the center of the grid to the beam projection was evaluated. The minimum jerk theoretical wave reduced the maximum-peak amplitude of radial tracking discrepancy compared with that of the waveforms modeled by cosine and typical free-breathing model by 22% and 35%, respectively, and provided smooth tracking for radial direction. Motion tracking constancy as indicated by radial tracking

Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle.

PubMed

Greggio, Chiara; Jha, Pooja; Kulkarni, Sameer S; Lagarrigue, Sylviane; Broskey, Nicholas T; Boutant, Marie; Wang, Xu; Conde Alonso, Sonia; Ofori, Emmanuel; Auwerx, Johan; Cantó, Carles; Amati, Francesca

2017-02-07

Mitochondrial dysfunction is a hallmark of multiple metabolic complications. Physical activity is known to increase mitochondrial content in skeletal muscle, counteracting age-related decline in muscle function and protecting against metabolic and cardiovascular complications. Here, we investigated the effect of 4 months of exercise training on skeletal muscle mitochondria electron transport chain complexes and supercomplexes in 26 healthy, sedentary older adults. Exercise differentially modulated respiratory complexes. Complex I was the most upregulated complex and not stoichiometrically associated to the other complexes. In contrast to the other complexes, complex I was almost exclusively found assembled in supercomplexes in muscle mitochondria. Overall, supercomplex content was increased after exercise. In particular, complexes I, III, and IV were redistributed to supercomplexes in the form of I+III 2 +IV. Taken together, our results provide the first evidence that exercise affects the stoichiometry of supercomplex formation in humans and thus reveal a novel adaptive mechanism for increased energy demand. Copyright © 2017 Elsevier Inc. All rights reserved.

Credit scores, cardiovascular disease risk, and human capital.

PubMed

Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

2014-12-02

Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

Credit scores, cardiovascular disease risk, and human capital

PubMed Central

Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W.; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E.

2014-01-01

Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions. PMID:25404329

Novel tools for blood inflammatory markers detection in monitoring air pollution-induced cardio-respiratory symptoms.

PubMed

Coccini, Teresa; Manzo, Luigi; De Simone, Uliana; Acerbi, Davide; Roda, Elisa

2012-01-01

There is strong epidemiological evidence that air pollution exposure (short- and long-term, i.e. < 24 hr to 3 weeks, and year/s) is related to exacerbation of cardiovascular and respiratory diseases. Data from toxicological and basic science/molecular studies, controlled animal and human exposures and human panel studies have demonstrated several mechanisms by which particle exposure may both trigger acute events as well as prompt the chronic development of cardiovascular diseases. These pollutant-mediated biological mechanisms are supporting the potential use of haematic (inflammation/coagulation/oxidative stress) markers of effects in cardio-respiratory diseases. Various examples from in vitro, in vivo and epidemiological investigations are reported, together with some novel technologies that should provide with new tools for research in these diseases and improve the knowledge about any linkage of local and systemic inflammation and clinical features of these diseases (in particular COPD), including lung function, exacerbations, disease progression, and mortality.

Computational Models and Emergent Properties of Respiratory Neural Networks

PubMed Central

Lindsey, Bruce G.; Rybak, Ilya A.; Smith, Jeffrey C.

2012-01-01

Computational models of the neural control system for breathing in mammals provide a theoretical and computational framework bringing together experimental data obtained from different animal preparations under various experimental conditions. Many of these models were developed in parallel and iteratively with experimental studies and provided predictions guiding new experiments. This data-driven modeling approach has advanced our understanding of respiratory network architecture and neural mechanisms underlying generation of the respiratory rhythm and pattern, including their functional reorganization under different physiological conditions. Models reviewed here vary in neurobiological details and computational complexity and span multiple spatiotemporal scales of respiratory control mechanisms. Recent models describe interacting populations of respiratory neurons spatially distributed within the Bötzinger and pre-Bötzinger complexes and rostral ventrolateral medulla that contain core circuits of the respiratory central pattern generator (CPG). Network interactions within these circuits along with intrinsic rhythmogenic properties of neurons form a hierarchy of multiple rhythm generation mechanisms. The functional expression of these mechanisms is controlled by input drives from other brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behavior of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple levels of circuit organization. This allows flexible, state-dependent expression of different neural pattern-generation mechanisms under various physiological conditions, enabling a wide repertoire of respiratory behaviors. Some models consider control of the respiratory CPG by pulmonary feedback and network reconfiguration during defensive behaviors such as cough. Future directions in modeling of the respiratory CPG are considered. PMID:23687564

Nation-wide surveillance of human acute respiratory virus infections between 2013 and 2015 in Korea.

PubMed

Kim, Jeong-Min; Jung, Hee-Dong; Cheong, Hyang-Min; Lee, Anna; Lee, Nam-Joo; Chu, Hyuk; Lee, Joo-Yeon; Kim, Sung Soon; Choi, Jang-Hoon

2018-07-01

The prevalence of eight respiratory viruses detected in patients with acute respiratory infections (ARIs) in Korea was investigated through analysis of data recorded by the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) from 2013 to 2015. Nasal aspirate and throat swabs specimens were collected from 36 915 patients with ARIs, and viral nucleic acids were detected by real-time (reverse-transcription) polymerase chain reaction for eight respiratory viruses, including human respiratory syncytial viruses (HRSVs), influenza viruses (IFVs), human parainfluenza viruses (HPIVs), human coronaviruses (HCoVs), human rhinovirus (HRV), human adenovirus (HAdV), human bocavirus (HBoV), and human metapneumovirus (HMPV). The overall positive rate of patient specimens was 49.4% (18 236/36 915), 5% of which carried two or more viruses simultaneously. HRV (15.6%) was the most predominantly detected virus, followed by IFVs (14.6%), HAdV (7.5%), HPIVs (5.8%), HCoVs (4.2%), HRSVs (3.6%), HBoV (1.9%), and HMPV (1.6%). Most of the ARIs were significantly correlated with clinical symptoms of fever, cough, and runny nose. Although HRV and HAdV were frequently detected throughout the year in patients, other respiratory viruses showed apparent seasonality. HRSVs and IFVs were the major causative agents of acute respiratory diseases in infants and young children. Overall, this study demonstrates a meaningful relationship between viral infection and typical manifestations of known clinical features as well as seasonality, age distribution, and co-infection among respiratory viruses. Therefore, these data could provide useful information for public health management and to enhance patient care for primary clinicians. © 2018 Wiley Periodicals, Inc.

A histological ontology of the human cardiovascular system.

PubMed

Mazo, Claudia; Salazar, Liliana; Corcho, Oscar; Trujillo, Maria; Alegre, Enrique

2017-10-02

In this paper, we describe a histological ontology of the human cardiovascular system developed in collaboration among histology experts and computer scientists. The histological ontology is developed following an existing methodology using Conceptual Models (CMs) and validated using OOPS!, expert evaluation with CMs, and how accurately the ontology can answer the Competency Questions (CQ). It is publicly available at http://bioportal.bioontology.org/ontologies/HO and https://w3id.org/def/System . The histological ontology is developed to support complex tasks, such as supporting teaching activities, medical practices, and bio-medical research or having natural language interactions.

Do environmental effects on human emotions cause cardiovascular disorders?

PubMed

Rosenman, R H

1997-01-01

Environmental influences on human health include the effects of toxic materials and adverse ecological factors. Natural milieu stressors also affect emotions that may adversely affect cardiovascular function and precipitate or otherwise contribute to complications of cardiovascular diseases. However, although variously hypothesized, there is inadequate evidence that they directly contribute to the pathogenesis of sustained hypertension or coronary atherosclerosis.

Promoting Cardiovascular Health in Patients Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

PubMed

Harris, Robin

2018-03-01

Patients living with human immunodeficiency virus/acquired immunodeficiency syndrome (PLWHA) are at increased risk of cardiovascular disease because of advances in human immunodeficiency virus/acquired immunodeficiency syndrome treatment and increased life expectancy. Cardiovascular health promotion in PLWHA includes strategies for risk factor reduction, disease prevention, early detection, and treatment of cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Farm Animal Models of Organic Dust Exposure and Toxicity: Insights and Implications for Respiratory Health

PubMed Central

McClendon, Chakia J.; Gerald, Carresse L.; Waterman, Jenora T.

2016-01-01

Purpose of review Modern food animal production is a major contributor to the global economy, owing to advanced intensive indoor production facilities aimed at increasing market readiness and profit. Consequences of these advances are accumulation of dusts, gases and microbial products that diminish air quality within production facilities. Chronic inhalation exposure contributes to onset and exacerbation of respiratory symptoms and diseases in animals and workers. This article reviews literature regarding constituents of farm animal production facility dusts; animal responses to production building and organic dust exposure, and the effect of chronic inhalation exposure on pulmonary oxidative stress and inflammation. Recent findings –Porcine models of production facility and organic dust exposures reveal striking similarities to observations of human cells, tissues and clinical data. Oxidative stress plays a key role in mediating respiratory diseases in animals and humans, and enhancement of antioxidant levels through nutritional supplements can improve respiratory health. Summary – Pigs are well adapted to the exposures common to swine production buildings and thus serve as excellent models for facility workers. Insight for understanding mechanisms governing organic dust associated respiratory diseases may come from parallel comparisons between farmers and the animals they raise. PMID:25636160

Possible Muscle Repair in the Human Cardiovascular System.

PubMed

Sommese, Linda; Zullo, Alberto; Schiano, Concetta; Mancini, Francesco P; Napoli, Claudio

2017-04-01

The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited and not a single piece of muscle can fully regrow after a severe injury. Therefore, muscle repair after myocardial infarction is still a chimera. Recently, it has been recognized that epigenetics could play a role in tissue regrowth since it guarantees the maintenance of cellular identity in differentiated cells and, therefore, the stability of organs and tissues. The removal of these locks can shift a specific cell identity back to the stem-like one. Given the gradual loss of tissue renewal potential in the course of evolution, in the last few years many different attempts to retrieve such potential by means of cell therapy approaches have been performed in experimental models. Here we review pathways and mechanisms involved in the in vivo repair of cardiovascular muscle tissues in humans. Moreover, we address the ongoing research on mammalian cardiac muscle repair based on adult stem cell transplantation and pro-regenerative factor delivery. This latter issue, involving genetic manipulations of adult cells, paves the way for developing possible therapeutic strategies in the field of cardiovascular muscle repair.

The short-term association of road traffic noise with cardiovascular, respiratory, and diabetes-related mortality.

PubMed

Recio, Alberto; Linares, Cristina; Banegas, José R; Díaz, Julio

2016-10-01

Road traffic noise has well-documented effects on cardiovascular, respiratory, and metabolic health. Numerous studies have reported long-term associations of urban noise with some diseases and outcomes, including death. However, to date there are no studies on the short-term association between this pollutant and a set of various specific causes of death. To investigate the short-term association of road traffic noise with daily cause-specific mortality. We used a time-stratified case-crossover design with Poisson regression. Predictor variables were daytime, nighttime, and 24-h equivalent noise levels, and maximum daytime and nighttime noise levels. Outcome variables were daily death counts for various specific causes, stratifying by age. We adjusted for primary air pollutants (PM2.5 and NO2) and weather conditions (mean temperature and relative humidity). In the ≥65 age group, increased mortality rates per 1 dBA increase in maximum nocturnal noise levels at lag 0 or 1 day were 2.9% (95% CI 1.0, 4.8%), 3.5% (95% CI 1.1, 6.1%), 2.4% (95% CI 0.1, 4.8%), 3.0% (95% CI 0.2, 5.8%), and 4.0% (95% CI 1.0, 7.0%), for ischemic heart disease, myocardial infarction, cerebrovascular disease, pneumonia, and COPD, respectively. For diabetes, 1 dBA increase in equivalent nocturnal noise levels at lag 1 was associated with an increased mortality rate of 11% (95% CI 4.0, 19%). In the <65 age group, increased mortality rates per 1 dBA increase in equivalent nocturnal noise levels at lag 0 were 11% (95% CI 4.2, 18%) and 11% (95% CI 4.2, 19%) for ischemic heart disease and myocardial infarction, respectively. Road traffic noise increases the short-term risk of death from specific diseases of the cardiovascular, respiratory, and metabolic systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Adaptation of the ICRP publication 66 respiratory tract model to data on plutonium biokinetics for Mayak workers.

PubMed

Khokhryakov, V F; Suslova, K G; Vostrotin, V V; Romanov, S A; Eckerman, K F; Krahenbuhl, M P; Miller, S C

2005-02-01

The biokinetics of inhaled plutonium were analyzed using compartment models representing their behavior within the respiratory tract, the gastrointestinal tract, and in systemic tissues. The processes of aerosol deposition, particle transport, absorption, and formation of a fixed deposit in the respiratory tract were formulated in the framework of the Human Respiratory Tract Model described in ICRP Publication 66. The values of parameters governing absorption and formation of the fixed deposit were established by fitting the model to the observations in 530 autopsy cases. The influence of smoking on mechanical clearance of deposited plutonium activity was considered. The dependence of absorption on the aerosol transportability, as estimated by in vitro methods (dialysis), was demonstrated. The results of this study were compared to those obtained from an earlier model of plutonium behavior in the respiratory tract, which was based on the same set of autopsy data. That model did not address the early phases of respiratory clearance and hence underestimated the committed lung dose by about 25% for plutonium oxides. Little difference in lung dose was found for nitrate forms.

Human torso phantom for imaging of heart with realistic modes of cardiac and respiratory motion

DOEpatents

Boutchko, Rostyslav; Balakrishnan, Karthikayan; Gullberg, Grant T; O& #x27; Neil, James P

2013-09-17

A human torso phantom and its construction, wherein the phantom mimics respiratory and cardiac cycles in a human allowing acquisition of medical imaging data under conditions simulating patient cardiac and respiratory motion.

Rapid generation of a mouse model for Middle East respiratory syndrome

PubMed Central

Zhao, Jincun; Li, Kun; Wohlford-Lenane, Christine; Agnihothram, Sudhakar S.; Fett, Craig; Zhao, Jingxian; Gale, Michael J.; Baric, Ralph S.; Enjuanes, Luis; Gallagher, Tom; McCray, Paul B.; Perlman, Stanley

2014-01-01

In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6–8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections. PMID:24599590

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

PubMed

Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

2015-12-10

Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of ovine hydatid cyst fluid on the cardiovascular and respiratory systems in sheep.

PubMed

Tabatabai, M; Ismaili, M H; Sami, M; Fardin, R; Kadivar, R

1975-01-01

Rupture of the hydatid cyst in man brings about mild to severe toxic reactions including death. The present study was undertaken to investigate some of the responses resulting from administration of the ovine hydatid fluid to the sheep, which, like man, is an intermediate host of the Echinococcus granulosus. In 50 sodium pentobarbital-anesthetized sheep, the arterial blood pressure (A.B.P.), central venous pressure (C.V.P.), respiration and electrocardiogram were recorded. Intraveonus administration of 5-10 ml hydatid fluid brought about moderate to severe fall in A.B.P. and rapid respiration with or without transient apnea or permanent repiratory cessation in 80 percent of the animals. Fifty percent of the sheep died of circulatory and respiratory failure after the first injection of the hydatid fluid. Boiled hydatid fluid did not lose its potency to evoke the above responses. Pretreatment of the aminals with atropine sulfate, 0,5 mg/kg subcutaneously, did not block the reactions. Administration of the antihistamine chlorpheniramine, 4 mg/kg intravenously, caused partial prevention of the reactions in 6 out of 10 responsive sheep. The cardiovascular and respiratory responses to ovine hydatid fluid may be due to antigen-antibody reactions or some toxic component of the fluid.

Fluid-structure interaction including volumetric coupling with homogenised subdomains for modeling respiratory mechanics.

PubMed

Yoshihara, Lena; Roth, Christian J; Wall, Wolfgang A

2017-04-01

In this article, a novel approach is presented for combining standard fluid-structure interaction with additional volumetric constraints to model fluid flow into and from homogenised solid domains. The proposed algorithm is particularly interesting for investigations in the field of respiratory mechanics as it enables the mutual coupling of airflow in the conducting part and local tissue deformation in the respiratory part of the lung by means of a volume constraint. In combination with a classical monolithic fluid-structure interaction approach, a comprehensive model of the human lung can be established that will be useful to gain new insights into respiratory mechanics in health and disease. To illustrate the validity and versatility of the novel approach, three numerical examples including a patient-specific lung model are presented. The proposed algorithm proves its capability of computing clinically relevant airflow distribution and tissue strain data at a level of detail that is not yet achievable, neither with current imaging techniques nor with existing computational models. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative Risks of Aldehyde Constituents in Cigarette Smoke Using Transient Computational Fluid Dynamics/Physiologically Based Pharmacokinetic Models of the Rat and Human Respiratory Tracts

PubMed Central

Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Jacob, Richard E.; Minard, Kevin R.; Teeguarden, Justin G.; Timchalk, Charles; Pipavath, Sudhakar; Glenny, Robb; Einstein, Daniel R.

2015-01-01

Computational fluid dynamics (CFD) modeling is well suited for addressing species-specific anatomy and physiology in calculating respiratory tissue exposures to inhaled materials. In this study, we overcame prior CFD model limitations to demonstrate the importance of realistic, transient breathing patterns for predicting site-specific tissue dose. Specifically, extended airway CFD models of the rat and human were coupled with airway region-specific physiologically based pharmacokinetic (PBPK) tissue models to describe the kinetics of 3 reactive constituents of cigarette smoke: acrolein, acetaldehyde and formaldehyde. Simulations of aldehyde no-observed-adverse-effect levels for nasal toxicity in the rat were conducted until breath-by-breath tissue concentration profiles reached steady state. Human oral breathing simulations were conducted using representative aldehyde yields from cigarette smoke, measured puff ventilation profiles and numbers of cigarettes smoked per day. As with prior steady-state CFD/PBPK simulations, the anterior respiratory nasal epithelial tissues received the greatest initial uptake rates for each aldehyde in the rat. However, integrated time- and tissue depth-dependent area under the curve (AUC) concentrations were typically greater in the anterior dorsal olfactory epithelium using the more realistic transient breathing profiles. For human simulations, oral and laryngeal tissues received the highest local tissue dose with greater penetration to pulmonary tissues than predicted in the rat. Based upon lifetime average daily dose comparisons of tissue hot-spot AUCs (top 2.5% of surface area-normalized AUCs in each region) and numbers of cigarettes smoked/day, the order of concern for human exposures was acrolein > formaldehyde > acetaldehyde even though acetaldehyde yields were 10-fold greater than formaldehyde and acrolein. PMID:25858911

Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

PubMed Central

Ng, Chun-Yi; Jaarin, Kamsiah

2015-01-01

Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

An experimental design for quantification of cardiovascular responses to music stimuli in humans.

PubMed

Chang, S-H; Luo, C-H; Yeh, T-L

2004-01-01

There have been several researches on the relationship between music and human physiological or psychological responses. However, there are cardiovascular index factors that have not been explored quantitatively due to the qualitative nature of acoustic stimuli. This study proposes and demonstrates an experimental design for quantification of cardiovascular responses to music stimuli in humans. The system comprises two components: a unit for generating and monitoring quantitative acoustic stimuli and a portable autonomic nervous system (ANS) analysis unit for quantitative recording and analysis of the cardiovascular responses. The experimental results indicate that the proposed system can exactly achieve the goal of full control and measurement for the music stimuli, and also effectively support many quantitative indices of cardiovascular response in humans. In addition, the analysis results are discussed and predicted in the future clinical research.

Computational Breakthrough of Natural Lead Hits from the Genus of Arisaema against Human Respiratory Syncytial Virus.

PubMed

Kant, Kamal; Lal, Uma Ranjan; Ghosh, Manik

2018-01-01

To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV. Selected 60 phytochemical entities were evaluated on the docking behavior of human RSV receptor (PDB: 4UCC) using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). Furthermore, kinetic properties and toxicity nature of top graded ligands were analyzed through QikProp and ProTox tools. Notably, rutin (glide score: -8.49), schaftoside (glide score: -8.18) and apigenin-6,8-di-C-β-D-galactoside (glide score - 7.29) have resulted in hopeful natural lead hits with an ideal range of kinetic descriptors values. ProTox tool (oral rodent toxicity) has resulted in likely toxicity targets of apex-graded tested ligands. Finally, the whole efforts can be explored further as a model to confirm its anti-human RSV potential with wet laboratory experiments. Rutin, schaftoside, and apigenin-6,8-di-C-β-D-galactoside showed promising top hits docking profile against human respiratory syncytial virusMoreover, absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptorsProTox tool highlighted toxicity class ranges, LD 50 values, and possible toxicity targets of apex-graded tested ligands. Abbreviations used: RSV: Respiratory syncytial virus, PRRSV: Porcine respiratory and reproductive syndrome virus, ADME-T: Absorption, distribution, metabolism, excretion, and toxicity.

Optimizing Cardiovascular Benefits of Exercise: A Review of Rodent Models

PubMed Central

Davis, Brittany; Moriguchi, Takeshi; Sumpio, Bauer

2013-01-01

Although research unanimously maintains that exercise can ward off cardiovascular disease (CVD), the optimal type, duration, intensity, and combination of forms are yet not clear. In our review of existing rodent-based studies on exercise and cardiovascular health, we attempt to find the optimal forms, intensities, and durations of exercise. Using Scopus and Medline, a literature review of English language comparative journal studies of cardiovascular benefits and exercise was performed. This review examines the existing literature on rodent models of aerobic, anaerobic, and power exercise and compares the benefits of various training forms, intensities, and durations. The rodent studies reviewed in this article correlate with reports on human subjects that suggest regular aerobic exercise can improve cardiac and vascular structure and function, as well as lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of rodent-based aerobic studies, but a lack of anaerobic and power forms of exercise, as well as comparisons of these three components of exercise. Thus, further studies must be conducted to determine a truly optimal regimen for cardiovascular health. PMID:24436579

Reductions in Cardiovascular, Cerebrovascular, and Respiratory Mortality following the National Irish Smoking Ban: Interrupted Time-Series Analysis

PubMed Central

Stallings-Smith, Sericea; Zeka, Ariana; Goodman, Pat; Kabir, Zubair; Clancy, Luke

2013-01-01

Background Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality. Methods A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence. Results Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76–0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63–0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54–0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46–0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35–64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32–0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305–4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking. Conclusions The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular

Human respiratory considerations for civil transport aircraft oxygen system.

DOT National Transportation Integrated Search

1978-01-01

This report is intended to acquaint personnel involved in the design, inspection, and maintenance of civil transport oxygen systems with the human respiratory requirements and oxygen system design considerations necessary to effect an interface and p...

Biology of obesity: lessons from animal models of obesity.

PubMed

Kanasaki, Keizo; Koya, Daisuke

2011-01-01

Obesity is an epidemic problem in the world and is associated with several health problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

Effect of human milk prostaglandins and lactoferrin on respiratory syncytial virus and rotavirus.

PubMed

Grover, M; Giouzeppos, O; Schnagl, R D; May, J T

1997-03-01

The effect of lactoferrin and prostaglandins E and F2 alpha on the growth of rotavirus and respiratory syncytial virus in cell culture was investigated. Lactoferrin inhibited the growth of respiratory syncytial virus at a concentration tenfold lower than that normally present in human milk. The prostaglandins had no effect on either virus growth, even at a concentration of 100-fold more than that found in human milk. Lactoferrin may have some antiviral properties in human milk in addition to its known antibacterial functions.

Multi-Scale Human Respiratory System Simulations to Study Health Effects of Aging, Disease, and Inhaled Substances

NASA Astrophysics Data System (ADS)

Kunz, Robert; Haworth, Daniel; Dogan, Gulkiz; Kriete, Andres

2006-11-01

Three-dimensional, unsteady simulations of multiphase flow, gas exchange, and particle/aerosol deposition in the human lung are reported. Surface data for human tracheo-bronchial trees are derived from CT scans, and are used to generate three- dimensional CFD meshes for the first several generations of branching. One-dimensional meshes for the remaining generations down to the respiratory units are generated using branching algorithms based on those that have been proposed in the literature, and a zero-dimensional respiratory unit (pulmonary acinus) model is attached at the end of each terminal bronchiole. The process is automated to facilitate rapid model generation. The model is exercised through multiple breathing cycles to compute the spatial and temporal variations in flow, gas exchange, and particle/aerosol deposition. The depth of the 3D/1D transition (at branching generation n) is a key parameter, and can be varied. High-fidelity models (large n) are run on massively parallel distributed-memory clusters, and are used to generate physical insight and to calibrate/validate the 1D and 0D models. Suitably validated lower-order models (small n) can be run on single-processor PC’s with run times that allow model-based clinical intervention for individual patients.

Spatial variation of multiple air pollutants and their potential contributions to all-cause, respiratory, and cardiovascular mortality across China in 2015-2016

NASA Astrophysics Data System (ADS)

Chen, Huan; Lin, Yun; Su, Qiong; Cheng, Liqiu

2017-11-01

Association of serious air pollution with adverse health effects in China has become a matter of public concern. However, many of studies that focused on a single air pollutant or a single city in China have rarely reflected the overall potential contribution of air pollution to unfavorable health outcomes. Therefore, our study estimated the spatial variation of particulate matter (PM2.5 and PM10) and gaseous pollutants (SO2, NO2, CO, and O3). Moreover, an additive approach was conducted to evaluate their overall potential contributions to mortality across China in 2015-2016 using the exposure-response coefficients. The results showed that cities with relatively high PM2.5 and PM10 concentrations were mainly distributed in the North China Plain (NCP). The average annual PM2.5 and PM10 concentrations in the NCP was 75.0 ± 14.7 and 131.2 ± 21.6 μg m-3. The potential contributions of six air pollutants ranged from 6.5% (95% confidence interval (CI): 5.4-7.5%) to 25.7% (95% CI: 22.2-28.9%) in all-cause mortality, from 6.5% (95% CI: 4.7-8.3%) to 24.9% (95% CI: 18.6-30.9%) in respiratory mortality, and from 7.0% (95% CI: 5.3-8.6%) to 29.5% (95% CI: 24.3-34.5%) in cardiovascular mortality. Many cities with high potential contributions of the multiple air pollutants were in the NCP. NCP had the average potential contribution of 20.0% (95% CI: 17.2-22.6%) in all-cause mortality, 19.5% (95% CI: 14.5-24.3%) in respiratory mortality, and 23.0% (95% CI: 18.8-27.0%) in cardiovascular mortality. Besides, the Taklimakan Desert (TD) also had high potential contribution of 19.9% (95% CI: 17.1-22.4%) in all-cause mortality, 19.5% (95% CI: 14.3-24.3%) in respiratory mortality, and 23.5% (95% CI: 19.2-27.5%) in cardiovascular mortality.

Chronic inhalation of carbon monoxide: effects on the respiratory and cardiovascular system at doses corresponding to tobacco smoking.

PubMed

Sørhaug, Sveinung; Steinshamn, Sigurd; Nilsen, Odd G; Waldum, Helge L

2006-12-07

Carbon monoxide (CO) is a dangerous poison in high concentrations, but the long-term effects of low doses of CO, as in the gaseous component of tobacco smoke, are not well known. The aims of our study were to evaluate the long-term effects of inhaled CO on the respiratory and cardiovascular system at doses corresponding to tobacco smoking and its effect on tumourigenesis and pulmonary neuroendocrine (NE) cells. Female Wistar rats were exposed to either CO (200 ppm) for 20 h/day (n=51) or air (n=26) for 72 weeks. Carboxyhaemoglobin was 14.7+/-0.3% in CO exposed animals and 0.3+/-0.1% in controls. In the lungs, no signs of pathology similar to that associated with cigarette smoking were observed, and no differences in number of pulmonary NE cells were observed between the groups. Chronic CO inhalation induced a 20% weight increase of the right ventricle (p=0.001) and a 14% weight increase of the left ventricle and interventricular septum (p<0.001). Histological examination of the myocardium did not reveal any signs of scarring. In the aorta and femoral artery, no signs of atherosclerosis were observed in CO exposed rats. No exposure related carcinogenic effects were observed. Spontaneous tumours were identified in 29% of CO exposed animals and in 28% of the controls. Our results suggest that low dose CO exposure is probably not responsible for the respiratory pathology associated with tobacco smoking. The effects on the cardiovascular system seem to involve myocardial hypertrophy, but not atherogenesis.

Mechanical model for simulating the conditioning of air in the respiratory tract.

PubMed

Bergonse Neto, Nelson; Von Bahten, Luiz Carlos; Moura, Luís Mauro; Coelho, Marlos de Souza; Stori Junior, Wilson de Souza; Bergonse, Gilberto da Fontoura Rey

2007-01-01

To create a mechanical model that could be regulated to simulate the conditioning of inspired and expired air with the same normal values of temperature, pressure, and relative humidity as those of the respiratory system of a healthy young man on mechanical ventilation. Using several types of materials, a mechanical device was built and regulated using normal values of vital capacity, tidal volume, maximal inspiratory pressure, positive end-expiratory pressure, and gas temperature in the system. The device was submitted to mechanical ventilation for a period of 29.8 min. The changes in the temperature of the air circulating in the system were recorded every two seconds. The statistical analysis of the data collected revealed that the device was approximately as efficient in the conditioning of air as is the respiratory system of a human being. By the study endpoint, we had developed a mechanical device capable of simulating the conditioning of air in the respiratory tract. The device mimics the conditions of temperature, pressure, and relative humidity seen in the respiratory system of healthy individuals.

Detection of human bocavirus and human metapneumovirus by real-time PCR from patients with respiratory symptoms in Southern Brazil.

PubMed

Pilger, Diogo André; Cantarelli, Vlademir Vicente; Amantea, Sérgio Luis; Leistner-Segal, Sandra

2011-02-01

The introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hMPV) and human bocavirus (hBoV), in respiratory tract specimens. We have studied the occurrence of hMPV and hBoV in the Porto Alegre (PA) metropolitan area, one of the southernmost cities of Brazil, evaluating children with suspected lower respiratory tract infection from May 2007-June 2008. A real-time polymerase chain reaction method was used for amplification and detection of hMPV and hBoV and to evaluate coinfections with respiratory syncytial virus (RSV), influenza A and B, parainfluenza 1, 2 and 3, human rhinovirus and human adenovirus. Of the 455 nasopharyngeal aspirates tested, hMPV was detected in 14.5% of samples and hBoV in 13.2%. A unique causative viral agent was identified in 46.2% samples and the coinfection rate was 43.7%. For hBoV, 98.3% of all positive samples were from patients with mixed infections. Similarly, 84.8% of all hMPV-positive results were also observed in mixed infections. Both hBoV and hMPV usually appeared with RSV. In summary, this is the first confirmation that hMPV and hBoV circulate in PA; this provides evidence of frequent involvement of both viruses in children with clinical signs of acute viral respiratory tract infection, although they mainly appeared as coinfection agents.

Cryptosporidium hominis Infection of the Human Respiratory Tract

PubMed Central

Buck, Gregory A.; Manque, Patricio A.; Ozaki, Luiz Shozo

2007-01-01

Cryptosporidium oocysts, observed in a natural sputum sample of a patient with HIV, were further studied by using DNA markers to determine the species of the parasite. C. hominis was identified as the species infecting the patient’s respiratory tract, a finding that strengthens evidence regarding this pathogen’s role in human disease. PMID:17552101

[The volume of surgery on the abdominal cavity organs in patients with associated cardiovascular and respiratory system diseases].

PubMed

Bondarenko, M V

2004-08-01

The cardiovascular and respiratory disturbances are the main risk factor in acute and chronic surgical deseases of the abdominal cavity organs, including oncological. It is limits the possibility and volume of the diagnostics and surgical tactics choice. The complicated current of main disease is a risk factor of operation perform and the reason of the undertaking inadequate and palliative intervention, which significant reduce of the quality of life. Real by risk level reductions in surgery is a determination of tissues viability, estimation of compensatory reserve sick evidences for determination for operation performance including simultaneous and staged.

Theoretical evaluation of burns to the human respiratory tract due to inhalation of hot gas in the early stage of fires.

PubMed

Lv, Yong-Gang; Liu, Jing; Zhang, Jun

2006-06-01

A transient two-dimensional mathematical model for heat and water vapor transport across the respiratory tract of human body was established and applied to predict the thermal impact of inhaled hot gas to the nasal tissues during the early stage of fires. Influences of individual's physiological status and environment variables were comprehensively investigated through numerical calculations. Burn evaluation was performed using the classical Henriques model to predict the time for thermal injury to occur. It was shown that decreasing the air velocity and increasing the respiratory rate is helpful to minimize the burn over the respiratory tract. The effect of relative humidity of surrounding dry hot air could be ignored in predicting burns for short duration exposures. Due to evaporation cooling on the mucousal membrane, the burn often occurs at certain positions underneath the skin of the tract near the inlet of the respiratory tract. Most of the tissues near the surface suffer injury immediately after exposure to fire, while in the deeper tissues, serious damage occurs after a relatively longer time period. The method presented in this paper may suggest a valuable approach to theoretically evaluate the injury of hot air to the human respiratory tract under various fire situations.

Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infection in Humans

PubMed Central

Zaas, Aimee K.; Chen, Minhua; Varkey, Jay; Veldman, Timothy; Hero, Alfred O.; Lucas, Joseph; Huang, Yongsheng; Turner, Ronald; Gilbert, Anthony; Lambkin-Williams, Robert; Øien, N. Christine; Nicholson, Bradly; Kingsmore, Stephen; Carin, Lawrence; Woods, Christopher W.; Ginsburg, Geoffrey S.

2010-01-01

Summary Acute respiratory infections (ARI) are a common reason for seeking medical attention and the threat of pandemic influenza will likely add to these numbers. Using human viral challenge studies with live rhinovirus, respiratory syncytial virus, and influenza A, we developed peripheral blood gene expression signatures that distinguish individuals with symptomatic ARI from uninfected individuals with > 95% accuracy. We validated this “acute respiratory viral” signature - encompassing genes with a known role in host defense against viral infections - across each viral challenge. We also validated the signature in an independently acquired dataset for influenza A and classified infected individuals from healthy controls with 100% accuracy. In the same dataset, we could also distinguish viral from bacterial ARIs (93% accuracy). These results demonstrate that ARIs induce changes in human peripheral blood gene expression that can be used to diagnose a viral etiology of respiratory infection and triage symptomatic individuals. PMID:19664979

LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.

PubMed

Gut, Philipp; Reischauer, Sven; Stainier, Didier Y R; Arnaout, Rima

2017-07-01

The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date. Copyright © 2017 the American Physiological Society.

Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

PubMed

Sharma, Arun; Wu, Joseph C; Wu, Sean M

2013-12-24

Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

An object-oriented computational model to study cardiopulmonary hemodynamic interactions in humans.

PubMed

Ngo, Chuong; Dahlmanns, Stephan; Vollmer, Thomas; Misgeld, Berno; Leonhardt, Steffen

2018-06-01

This work introduces an object-oriented computational model to study cardiopulmonary interactions in humans. Modeling was performed in object-oriented programing language Matlab Simscape, where model components are connected with each other through physical connections. Constitutive and phenomenological equations of model elements are implemented based on their non-linear pressure-volume or pressure-flow relationship. The model includes more than 30 physiological compartments, which belong either to the cardiovascular or respiratory system. The model considers non-linear behaviors of veins, pulmonary capillaries, collapsible airways, alveoli, and the chest wall. Model parameters were derisved based on literature values. Model validation was performed by comparing simulation results with clinical and animal data reported in literature. The model is able to provide quantitative values of alveolar, pleural, interstitial, aortic and ventricular pressures, as well as heart and lung volumes during spontaneous breathing and mechanical ventilation. Results of baseline simulation demonstrate the consistency of the assigned parameters. Simulation results during mechanical ventilation with PEEP trials can be directly compared with animal and clinical data given in literature. Object-oriented programming languages can be used to model interconnected systems including model non-linearities. The model provides a useful tool to investigate cardiopulmonary activity during spontaneous breathing and mechanical ventilation. Copyright © 2018 Elsevier B.V. All rights reserved.

Longitudinal modelling of respiratory symptoms in children

NASA Astrophysics Data System (ADS)

Schlink, Uwe; Fritz, Gisela; Herbarth, Olf; Richter, Matthias

2002-08-01

A panel of 277 children, aged 3-7 years, was used to study the association between air pollution (O3, SO2, NO2, and total suspended particles), meteorological factors (global radiation, maximum daytime temperature, daily averages of vapour pressure and air humidity) and respiratory symptoms. For 759 days the symptoms were recorded in a diary and modelling was based on a modification of the method proposed by Korn and Whittemore (Biometrics 35: 795-798, 1979). This approach (1) comprises an extension using environmental parameters at different time scales, (2) addresses the suitability of using the daily fraction of symptomatic individuals to account for inter-individual interactions and (3) enables the most significant weather effects to be identified. The resulting model consisted of (1) an individual specific intercept that takes account of the population's heterogeneity, (2) the individual's health status the day before, (3) a long-term meteorological effect, which may be either the squared temperature or global radiation in interaction with temperature, (4) the short-term effect of sulfur dioxide, and (5) the short-term effect of an 8-h ozone concentration above 60 µg/m3. Using the estimated parameters as input to a simulation study, we checked the quality of the model and demonstrate that the annual cycle of the prevalence of respiratory symptoms is associated to atmospheric covariates. Individuals suffering from allergy have been identified as a group of a particular susceptibility to ozone. The duration of respiratory symptoms appears to be free of scale and follows an exponential distribution function, which confirms that the symptom record of each individual follows a Poisson point-process. This supports the assumption that not only respiratory diseases, but also respiratory symptoms can be considered an independent measure for the health status of a population sample. Since a point process is described by only one parameter (namely the intensity of the

Respiratory health in Latin America: number of specialists and human resources training.

PubMed

Vázquez-García, Juan-Carlos; Salas-Hernández, Jorge; Pérez Padilla, Rogelio; Montes de Oca, María

2014-01-01

Latin America is made up of a number of developing countries. Demographic changes are occurring in the close to 600 million inhabitants, in whom a significant growth in population is combined with the progressive ageing of the population. This part of the world poses great challenges for general and respiratory health. Most of the countries have significant, or even greater, rates of chronic respiratory diseases or exposure to risk. Human resources in healthcare are not readily available, particularly in the area of respiratory disease specialists. Academic training centers are few and even non-existent in the majority of the countries. The detailed analysis of these conditions provides a basis for reflection on the main challenges and proposals for the management and training of better human resources in this specialist area. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Using a respiratory navigator significantly reduces variability when quantifying left ventricular torsion with cardiovascular magnetic resonance.

PubMed

Hamlet, Sean M; Haggerty, Christopher M; Suever, Jonathan D; Wehner, Gregory J; Andres, Kristin N; Powell, David K; Charnigo, Richard J; Fornwalt, Brandon K

2017-03-01

Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion. We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure and then enforce variability in end-expiratory position between all LV basal and apical acquisitions. From these data, we quantified the inter-test variability of torsion in the absence and presence of enforced end-expiratory position variability, which established an upper bound for the expected torsion variability. For the second experiment (in 20 new, healthy volunteers), 10 pairs of cine DENSE basal and apical images were each acquired from consecutive breath-holds and consecutive navigator-gated scans (with a single acceptance position). Inter-test variability of torsion was compared between the breath-hold and navigator-gated scans to quantify the variability due to natural breath-hold variation. To demonstrate the importance of these variability reductions, we quantified the reduction in sample size required to detect a clinically meaningful change in LV torsion with the use of a respiratory navigator. The mean torsion was 3.4 ± 0.2°/cm. From the first experiment, enforced variability in end-expiratory position translated to considerable variability in measured torsion (0.56 ± 0.34°/cm), whereas inter-test variability with consistent end-expiratory position was 57% lower (0.24 ± 0.16°/cm, p < 0.001). From the second experiment, natural

Associations between air temperature and cardio-respiratory mortality in the urban area of Beijing, China: a time-series analysis.

PubMed

Liu, Liqun; Breitner, Susanne; Pan, Xiaochuan; Franck, Ulrich; Leitte, Arne Marian; Wiedensohler, Alfred; von Klot, Stephanie; Wichmann, H-Erich; Peters, Annette; Schneider, Alexandra

2011-05-25

Associations between air temperature and mortality have been consistently observed in Europe and the United States; however, there is a lack of studies for Asian countries. Our study investigated the association between air temperature and cardio-respiratory mortality in the urban area of Beijing, China. Death counts for cardiovascular and respiratory diseases for adult residents (≥15 years), meteorological parameters and concentrations of particulate air pollution were obtained from January 2003 to August 2005. The effects of two-day and 15-day average temperatures were estimated by Poisson regression models, controlling for time trend, relative humidity and other confounders if necessary. Effects were explored for warm (April to September) and cold periods (October to March) separately. The lagged effects of daily temperature were investigated by polynomial distributed lag (PDL) models. We observed a J-shaped exposure-response function only for 15-day average temperature and respiratory mortality in the warm period, with 21.3°C as the threshold temperature. All other exposure-response functions could be considered as linear. In the warm period, a 5°C increase of two-day average temperature was associated with a RR of 1.098 (95% confidence interval (95%CI): 1.057-1.140) for cardiovascular and 1.134 (95%CI: 1.050-1.224) for respiratory mortality; a 5°C decrease of 15-day average temperature was associated with a RR of 1.040 (95%CI: 0.990-1.093) for cardiovascular mortality. In the cold period, a 5°C increase of two-day average temperature was associated with a RR of 1.149 (95%CI: 1.078-1.224) for respiratory mortality; a 5°C decrease of 15-day average temperature was associated with a RR of 1.057 (95%CI: 1.022-1.094) for cardiovascular mortality. The effects remained robust after considering particles as additional confounders. Both increases and decreases in air temperature are associated with an increased risk of cardiovascular mortality. The effects of

Associations between air temperature and cardio-respiratory mortality in the urban area of Beijing, China: a time-series analysis

PubMed Central

2011-01-01

Background Associations between air temperature and mortality have been consistently observed in Europe and the United States; however, there is a lack of studies for Asian countries. Our study investigated the association between air temperature and cardio-respiratory mortality in the urban area of Beijing, China. Methods Death counts for cardiovascular and respiratory diseases for adult residents (≥15 years), meteorological parameters and concentrations of particulate air pollution were obtained from January 2003 to August 2005. The effects of two-day and 15-day average temperatures were estimated by Poisson regression models, controlling for time trend, relative humidity and other confounders if necessary. Effects were explored for warm (April to September) and cold periods (October to March) separately. The lagged effects of daily temperature were investigated by polynomial distributed lag (PDL) models. Results We observed a J-shaped exposure-response function only for 15-day average temperature and respiratory mortality in the warm period, with 21.3°C as the threshold temperature. All other exposure-response functions could be considered as linear. In the warm period, a 5°C increase of two-day average temperature was associated with a RR of 1.098 (95% confidence interval (95%CI): 1.057-1.140) for cardiovascular and 1.134 (95%CI: 1.050-1.224) for respiratory mortality; a 5°C decrease of 15-day average temperature was associated with a RR of 1.040 (95%CI: 0.990-1.093) for cardiovascular mortality. In the cold period, a 5°C increase of two-day average temperature was associated with a RR of 1.149 (95%CI: 1.078-1.224) for respiratory mortality; a 5°C decrease of 15-day average temperature was associated with a RR of 1.057 (95%CI: 1.022-1.094) for cardiovascular mortality. The effects remained robust after considering particles as additional confounders. Conclusions Both increases and decreases in air temperature are associated with an increased risk of

Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

PubMed Central

Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

2018-01-01

Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and

Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria.

PubMed

Broniarek, Izabela; Jarmuszkiewicz, Wieslawa

2018-01-01

The purpose of this research was to elucidate the direct effects of two popular blood cholesterol-lowering drugs used to treat cardiovascular diseases, atorvastatin and pravastatin, on respiratory function, membrane potential, and reactive oxygen species formation in mitochondria isolated from human umbilical vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not significantly affect endothelial mitochondria function. In contrast, hydrophobic calcium-containing atorvastatin induced a loss of outer mitochondrial membrane integrity, an increase in hydrogen peroxide formation, and reductions in maximal (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative phosphorylation efficiency. The atorvastatin-induced changes indicate an impairment of mitochondrial function at the level of ATP synthesis and at the level of the respiratory chain, likely at complex I and complex III. The atorvastatin action on endothelial mitochondria was highly dependent on calcium ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of calcium ions included in atorvastatin molecule induced mitochondrial uncoupling that enhanced the inhibition of the mitochondrial respiratory chain by atorvastatin. Our results indicate that hydrophobic calcium-containing atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative action on isolated endothelial mitochondria. Copyright © 2017. Published by Elsevier Inc.

Sleep apnea and cardiovascular risk.

PubMed

Floras, John S

2014-01-01

Sleep apnea is evident in approximately 10% of adults in the general population, but in certain cardiovascular diseases, and in particular those characterized by sodium and water retention, its prevalence can exceed 50%. Although sleep apnea is not as yet integrated into formal cardiovascular risk assessment algorithms, there is increasing awareness of its importance in the causation or promotion of hypertension, coronary artery disease, heart failure, atrial arrhythmias, and stroke, and thus, not surprisingly, as a predictor of premature cardiovascular death. Sleep apnea manifests as two principal phenotypes, both characterized by respiratory instability: obstructive (OSA), which arises when sleep-related withdrawal of respiratory drive to the upper airway dilator muscles is superimposed upon a narrow and highly compliant airway predisposed to collapse, and central (CSA), which occurs when the partial pressure of arterial carbon dioxide falls below the apnea threshold, resulting in withdrawal of central drive to respiratory muscles. The present objectives are to: (1) review the epidemiology and patho-physiology of OSA and CSA, with particular emphasis on the role of renal sodium retention in initiating and promoting these processes, and on population studies that reveal the long-term consequences of untreated OSA and CSA; (2) illustrate mechanical, autonomic, chemical, and inflammatory mechanisms by which OSA and CSA can increase cardiovascular risk and event rates by initiating or promoting hypertension, atherosclerosis, coronary artery disease, heart failure, arrhythmias, and stroke; (3) highlight insights from randomized trials in which treating sleep apnea was the specific target of therapy; (4) emphasize the present lack of evidence that treating sleep apnea reduces cardiovascular risk and the current clinical equipoise concerning treatment of asymptomatic patients with sleep apnea; and (5) consider clinical implications and future directions of clinical

Simulating physiological interactions in a hybrid system of mathematical models.

PubMed

Kretschmer, Jörn; Haunsberger, Thomas; Drost, Erick; Koch, Edmund; Möller, Knut

2014-12-01

Mathematical models can be deployed to simulate physiological processes of the human organism. Exploiting these simulations, reactions of a patient to changes in the therapy regime can be predicted. Based on these predictions, medical decision support systems (MDSS) can help in optimizing medical therapy. An MDSS designed to support mechanical ventilation in critically ill patients should not only consider respiratory mechanics but should also consider other systems of the human organism such as gas exchange or blood circulation. A specially designed framework allows combining three model families (respiratory mechanics, cardiovascular dynamics and gas exchange) to predict the outcome of a therapy setting. Elements of the three model families are dynamically combined to form a complex model system with interacting submodels. Tests revealed that complex model combinations are not computationally feasible. In most patients, cardiovascular physiology could be simulated by simplified models decreasing computational costs. Thus, a simplified cardiovascular model that is able to reproduce basic physiological behavior is introduced. This model purely consists of difference equations and does not require special algorithms to be solved numerically. The model is based on a beat-to-beat model which has been extended to react to intrathoracic pressure levels that are present during mechanical ventilation. The introduced reaction to intrathoracic pressure levels as found during mechanical ventilation has been tuned to mimic the behavior of a complex 19-compartment model. Tests revealed that the model is able to represent general system behavior comparable to the 19-compartment model closely. Blood pressures were calculated with a maximum deviation of 1.8 % in systolic pressure and 3.5 % in diastolic pressure, leading to a simulation error of 0.3 % in cardiac output. The gas exchange submodel being reactive to changes in cardiac output showed a resulting deviation of less

Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations.

PubMed

Mateika, Jason H; Syed, Ziauddin

2013-09-15

This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. Published by Elsevier B.V.

Three-Dimensional Engineered High Fidelity Normal Human Lung Tissue-Like Assemblies (TLA) as Targets for Human Respiratory Virus Infections

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; Deatly, A. M.; Suderman, M. T.; Lin, Y.-H.; Chen, W.; Gupta, C. K.; Randolph, V. B.; Udem, S. A.

2003-01-01

Unlike traditional two-dimensional (2D) cell cultures, three-dimensional (3D) tissue-like assemblies (TLA) (Goodwin et aI, 1992, 1993, 2000 and Nickerson et aI. , 2001,2002) offer high organ fidelity with the potential to emulate the infective dynamics of viruses and bacteria in vivo. Thus, utilizing NASA micro gravity Rotating Wall Vessel (RWV) technology, in vitro human broncho-epithelial (HBE) TLAs were engineered to mimic in vivo tissue for study of human respiratory viruses. These 3D HBE TLAs were propagated from a human broncho-tracheal cell line with a mesenchymal component (HBTC) as the foundation matrix and either an adult human broncho-epithelial cell (BEAS-2B) or human neonatal epithelial cell (16HBE140-) as the overlying element. Resulting TLAs share several characteristic features with in vivo human respiratory epithelium including tight junctions, desmosomes and cilia (SEM, TEM). The presence of epithelium and specific lung epithelium markers furthers the contention that these HBE cells differentiate into TLAs paralleling in vivo tissues. A time course of infection of these 3D HBE TLAs with human respiratory syncytial virus (hRSV) wild type A2 strain, indicates that virus replication and virus budding are supported and manifested by increasing virus titer and detection of membrane-bound F and G glycoproteins. Infected 3D HBE TLAs remain intact for up to 12 days compared to infected 2D cultures that are destroyed in 2-3 days. Infected cells show an increased vacuolation and cellular destruction (by transmission electron microscopy) by day 9; whereas, uninfected cells remain robust and morphologically intact. Therefore, the 3D HBE TLAs mimic aspects of human respiratory epithelium providing a unique opportunity to analyze, for the first time, simulated in vivo viral infection independent of host immune response.

The significance of Candida in the human respiratory tract: our evolving understanding.

PubMed

Pendleton, Kathryn M; Huffnagle, Gary B; Dickson, Robert P

2017-04-01

Candida is an opportunistic pathogen and the most commonly isolated fungal genus in humans. Though Candida is often detected in respiratory specimens from humans with and without lung disease, its significance remains undetermined. While historically considered a commensal organism with low virulence potential, the status of Candida as an innocent bystander has recently been called into question by both clinical observations and animal experimentation. We here review what is currently known and yet to be determined about the clinical, microbiological and pathophysiological significance of the detection of Candida spp. in the human respiratory tract. Published by Oxford University Press on behalf of FEMS 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Nine months in space: effects on human autonomic cardiovascular regulation.

PubMed

Cooke, W H; Ames JE, I V; Crossman, A A; Cox, J F; Kuusela, T A; Tahvanainen, K U; Moon, L B; Drescher, J; Baisch, F J; Mano, T; Levine, B D; Blomqvist, C G; Eckberg, D L

2000-09-01

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.

Computational fluid dynamics modelling in cardiovascular medicine

PubMed Central

Morris, Paul D; Narracott, Andrew; von Tengg-Kobligk, Hendrik; Silva Soto, Daniel Alejandro; Hsiao, Sarah; Lungu, Angela; Evans, Paul; Bressloff, Neil W; Lawford, Patricia V; Hose, D Rodney; Gunn, Julian P

2016-01-01

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards ‘digital patient’ or ‘virtual physiological human’ representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges. PMID:26512019

The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

PubMed Central

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

2015-01-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

Modeling Respiratory Toxicity of Authentic Lunar Dust

NASA Technical Reports Server (NTRS)

Santana, Patricia A.; James, John T.; Lam, Chiu-Wing

2010-01-01

The lunar expeditions of the Apollo operations from the 60 s and early 70 s have generated awareness about lunar dust exposures and their implication towards future lunar explorations. Critical analyses on the reports from the Apollo crew members suggest that lunar dust is a mild respiratory and ocular irritant. Currently, NASA s space toxicology group is functioning with the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) and the National Institute for Occupational Safety and Health (NIOSH) to investigate and examine toxic effects to the respiratory system of rats in order to establish permissible exposure levels (PELs) for human exposure to lunar dust. In collaboration with the space toxicology group, LADTAG and NIOSH the goal of the present research is to analyze dose-response curves from rat exposures seven and twenty-eight days after intrapharyngeal instillations, and model the response using BenchMark Dose Software (BMDS) from the Environmental Protection Agency (EPA). Via this analysis, the relative toxicities of three types of Apollo 14 lunar dust samples and two control dust samples, titanium dioxide (TiO2) and quartz will be determined. This will be executed for several toxicity endpoints such as cell counts and biochemical markers in bronchoaveolar lavage fluid (BALF) harvested from the rats.

Replication of H9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release.

PubMed

Chan, Renee W Y; Chan, Louisa L Y; Mok, Chris K P; Lai, Jimmy; Tao, Kin P; Obadan, Adebimpe; Chan, Michael C W; Perez, Daniel R; Peiris, J S Malik; Nicholls, John M

2017-07-24

H9N2 viruses are the most widespread influenza viruses in poultry in Asia. We evaluated the infection and tropism of human and avian H9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture. H9 viruses infected the upper and lower respiratory tract and the majority of H9 viruses had a decreased ability to release virus from the bronchus rather than the lung. This may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic acid (Sia) rather than carbon-3-linked Sia. The modified cleavage of N-acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in H9 virus replication was observed by reverse genetics, and recombinant H9N2 viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino acid at position 431 from Proline-to-Lysine. Using recombinant H9 viruses previously evaluated in the ferret, we found that viruses which replicated well in the ferret did not replicate to the same extent in the human ex vivo cultures. The existing risk assessment models for H9N2 viruses in ferrets may not always have a strong correlation with the replication in the human upper respiratory tract. The inclusion of the human ex vivo cultures would further strengthen the future risk-assessment strategies.

Serologic Cross-Reactions between Nucleocapsid Proteins of Human Respiratory Syncytial Virus and Human Metapneumovirus

PubMed Central

Zhang, Yange; Pohl, Jan; Brooks, W. Abdullah

2015-01-01

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) share virologic and epidemiologic features and cause clinically similar respiratory illness predominantly in young children. In a previous study of acute febrile respiratory illness in Bangladesh, we tested paired serum specimens from 852 children presenting fever and cough for diagnostic increases in titers of antibody to hRSV and hMPV by enzyme immunoassay (EIA). Unexpectedly, of 93 serum pairs that showed a ≥4-fold increase in titers of antibody to hRSV, 24 (25.8%) showed a concurrent increase in titers of antibody to hMPV; of 91 pairs showing an increase to hMPV, 13 (14.3%) showed a concurrent increase to hRSV. We speculated that common antigens shared by these viruses explain this finding. Since the nucleocapsid (N) proteins of these viruses show the greatest sequence homology, we tested hyperimmune antisera prepared for each virus against baculovirus-expressed recombinant N (recN) proteins for potential cross-reactivity. The antisera were reciprocally reactive with both proteins. To localize common antigenic regions, we first expressed the carboxy domain of the hMPV N protein that was the most highly conserved region within the hRSV N protein. Although reciprocally reactive with antisera by Western blotting, this truncated protein did not react with hMPV IgG-positive human sera by EIA. Using 5 synthetic peptides that spanned the amino-terminal portion of the hMPV N protein, we identified a single peptide that was cross-reactive with human sera positive for either virus. Antiserum prepared for this peptide was reactive with recN proteins of both viruses, indicating that a common immunoreactive site exists in this region. PMID:25740767

Serologic cross-reactions between nucleocapsid proteins of human respiratory syncytial virus and human metapneumovirus.

PubMed

Zhang, Yange; Pohl, Jan; Brooks, W Abdullah; Erdman, Dean D

2015-05-01

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) share virologic and epidemiologic features and cause clinically similar respiratory illness predominantly in young children. In a previous study of acute febrile respiratory illness in Bangladesh, we tested paired serum specimens from 852 children presenting fever and cough for diagnostic increases in titers of antibody to hRSV and hMPV by enzyme immunoassay (EIA). Unexpectedly, of 93 serum pairs that showed a ≥ 4-fold increase in titers of antibody to hRSV, 24 (25.8%) showed a concurrent increase in titers of antibody to hMPV; of 91 pairs showing an increase to hMPV, 13 (14.3%) showed a concurrent increase to hRSV. We speculated that common antigens shared by these viruses explain this finding. Since the nucleocapsid (N) proteins of these viruses show the greatest sequence homology, we tested hyperimmune antisera prepared for each virus against baculovirus-expressed recombinant N (recN) proteins for potential cross-reactivity. The antisera were reciprocally reactive with both proteins. To localize common antigenic regions, we first expressed the carboxy domain of the hMPV N protein that was the most highly conserved region within the hRSV N protein. Although reciprocally reactive with antisera by Western blotting, this truncated protein did not react with hMPV IgG-positive human sera by EIA. Using 5 synthetic peptides that spanned the amino-terminal portion of the hMPV N protein, we identified a single peptide that was cross-reactive with human sera positive for either virus. Antiserum prepared for this peptide was reactive with recN proteins of both viruses, indicating that a common immunoreactive site exists in this region. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Respiratory hazard assessment of combined exposure to complete gasoline exhaust and respirable volcanic ash in a multicellular human lung model at the air-liquid interface

USGS Publications Warehouse

Tomasek, Ines; Horwell, Claire J.; Bisig, Christoph; Damby, David; Comte, Pierre; Czerwinski, Jan; Petri-Fink, Alke; Clift, Martin J D; Drasler, Barbara; Rothen-Rutishauer, Barbara

2018-01-01

Communities resident in urban areas located near active volcanoes can experience volcanic ash exposures during, and following, an eruption, in addition to sustained exposures to high concentrations of anthropogenic air pollutants (e.g., vehicle exhaust emissions). Inhalation of anthropogenic pollution is known to cause the onset of, or exacerbate, respiratory and cardiovascular diseases. It is further postulated similar exposure to volcanic ash can also affect such disease states. Understanding of the impact of combined exposure of volcanic ash and anthropogenic pollution to human health, however, remains limited.The aim of this study was to assess the biological impact of combined exposure to respirable volcanic ash (from Soufrière Hills volcano (SHV), Montserrat and Chaitén volcano (ChV), Chile; representing different magmatic compositions and eruption styles) and freshly-generated complete exhaust from a gasoline vehicle. A multicellular human lung model (an epithelial cell-layer composed of A549 alveolar type II-like cells complemented with human blood monocyte-derived macrophages and dendritic cells cultured at the air-liquid interface) was exposed to diluted exhaust (1:10) continuously for 6 h, followed by immediate exposure to the ash as a dry powder (0.54 ± 0.19 μg/cm2 and 0.39 ± 0.09 μg/cm2 for SHV and ChV ash, respectively). After an 18 h incubation, cells were exposed again for 6 h to diluted exhaust, and a final 18 h incubation (at 37 °C and 5% CO2). Cell cultures were then assessed for cytotoxic, oxidative stress and (pro-)inflammatory responses.Results indicate that, at all tested (sub-lethal) concentrations, co-exposures with both ash samples induced no significant expression of genes associated with oxidative stress (HMOX1, NQO1) or production of (pro-)inflammatory markers (IL-1β, IL-8, TNF-α) at the gene and protein levels. In summary, considering the employed experimental conditions, combined exposure of

Respiratory hazard assessment of combined exposure to complete gasoline exhaust and respirable volcanic ash in a multicellular human lung model at the air-liquid interface.

PubMed

Tomašek, Ines; Horwell, Claire J; Bisig, Christoph; Damby, David E; Comte, Pierre; Czerwinski, Jan; Petri-Fink, Alke; Clift, Martin J D; Drasler, Barbara; Rothen-Rutishauser, Barbara

2018-07-01

Communities resident in urban areas located near active volcanoes can experience volcanic ash exposures during, and following, an eruption, in addition to sustained exposures to high concentrations of anthropogenic air pollutants (e.g., vehicle exhaust emissions). Inhalation of anthropogenic pollution is known to cause the onset of, or exacerbate, respiratory and cardiovascular diseases. It is further postulated similar exposure to volcanic ash can also affect such disease states. Understanding of the impact of combined exposure of volcanic ash and anthropogenic pollution to human health, however, remains limited. The aim of this study was to assess the biological impact of combined exposure to respirable volcanic ash (from Soufrière Hills volcano (SHV), Montserrat and Chaitén volcano (ChV), Chile; representing different magmatic compositions and eruption styles) and freshly-generated complete exhaust from a gasoline vehicle. A multicellular human lung model (an epithelial cell-layer composed of A549 alveolar type II-like cells complemented with human blood monocyte-derived macrophages and dendritic cells cultured at the air-liquid interface) was exposed to diluted exhaust (1:10) continuously for 6 h, followed by immediate exposure to the ash as a dry powder (0.54 ± 0.19 μg/cm 2 and 0.39 ± 0.09 μg/cm 2 for SHV and ChV ash, respectively). After an 18 h incubation, cells were exposed again for 6 h to diluted exhaust, and a final 18 h incubation (at 37 °C and 5% CO 2 ). Cell cultures were then assessed for cytotoxic, oxidative stress and (pro-)inflammatory responses. Results indicate that, at all tested (sub-lethal) concentrations, co-exposures with both ash samples induced no significant expression of genes associated with oxidative stress (HMOX1, NQO1) or production of (pro-)inflammatory markers (IL-1β, IL-8, TNF-α) at the gene and protein levels. In summary, considering the employed experimental conditions, combined exposure of

Human Cardiovascular Responses to Passive Heat Stress

PubMed Central

Crandall, Craig G.; Wilson, Thad E.

2016-01-01

Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur. PMID:25589263

Acute respiratory and cardiovascular admissions after a public smoking ban in Geneva, Switzerland.

PubMed

Humair, Jean-Paul; Garin, Nicolas; Gerstel, Eric; Carballo, Sebastian; Carballo, David; Keller, Pierre-Frédéric; Guessous, Idris

2014-01-01

Many countries have introduced legislations for public smoking bans to reduce the harmful effects of exposure to tobacco smoke. Smoking bans cause significant reductions in admissions for acute coronary syndromes but their impact on respiratory diseases is unclear. In Geneva, Switzerland, two popular votes led to a stepwise implementation of a state smoking ban in public places, with a temporary suspension. This study evaluated the effect of this smoking ban on hospitalisations for acute respiratory and cardiovascular diseases. This before and after intervention study was conducted at the University Hospitals of Geneva, Switzerland, across 4 periods with different smoking legislations. It included 5,345 patients with a first hospitalisation for acute coronary syndrome, ischemic stroke, acute exacerbation of chronic obstructive pulmonary disease, pneumonia and acute asthma. The main outcomes were the incidence rate ratios (IRR) of admissions for each diagnosis after the final ban compared to the pre-ban period and adjusted for age, gender, season, influenza epidemic and secular trend. Hospitalisations for acute exacerbation of chronic obstructive pulmonary disease significantly decreased over the 4 periods and were lowest after the final ban (IRR=0.54 [95%CI: 0.42-0.68]). We observed a trend in reduced admissions for acute coronary syndromes (IRR=0.90 [95%CI: 0.80-1.00]). Admissions for ischemic stroke, asthma and pneumonia did not significantly change. A legislative smoking ban was followed by a strong decrease in hospitalisations for acute exacerbation of chronic obstructive pulmonary disease and a trend for reduced admissions for acute coronary syndrome. Smoking bans are likely to be very beneficial for patients with chronic obstructive pulmonary disease.

Acute Respiratory and Cardiovascular Admissions after a Public Smoking Ban in Geneva, Switzerland

PubMed Central

Humair, Jean-Paul; Garin, Nicolas; Gerstel, Eric; Carballo, Sebastian; Carballo, David; Keller, Pierre-Frédéric; Guessous, Idris

2014-01-01

Background Many countries have introduced legislations for public smoking bans to reduce the harmful effects of exposure to tobacco smoke. Smoking bans cause significant reductions in admissions for acute coronary syndromes but their impact on respiratory diseases is unclear. In Geneva, Switzerland, two popular votes led to a stepwise implementation of a state smoking ban in public places, with a temporary suspension. This study evaluated the effect of this smoking ban on hospitalisations for acute respiratory and cardiovascular diseases. Methods This before and after intervention study was conducted at the University Hospitals of Geneva, Switzerland, across 4 periods with different smoking legislations. It included 5,345 patients with a first hospitalisation for acute coronary syndrome, ischemic stroke, acute exacerbation of chronic obstructive pulmonary disease, pneumonia and acute asthma. The main outcomes were the incidence rate ratios (IRR) of admissions for each diagnosis after the final ban compared to the pre-ban period and adjusted for age, gender, season, influenza epidemic and secular trend. Results Hospitalisations for acute exacerbation of chronic obstructive pulmonary disease significantly decreased over the 4 periods and were lowest after the final ban (IRR = 0.54 [95%CI: 0.42–0.68]). We observed a trend in reduced admissions for acute coronary syndromes (IRR = 0.90 [95%CI: 0.80–1.00]). Admissions for ischemic stroke, asthma and pneumonia did not significantly change. Conclusions A legislative smoking ban was followed by a strong decrease in hospitalisations for acute exacerbation of chronic obstructive pulmonary disease and a trend for reduced admissions for acute coronary syndrome. Smoking bans are likely to be very beneficial for patients with chronic obstructive pulmonary disease. PMID:24599156

Mathematical modeling of the human body during water replacement and dehydration: body water changes.

PubMed

Downey, D; Seagrave, R C

2000-03-01

A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model.

A respiratory alert model for the Shenandoah Valley, Virginia, USA

NASA Astrophysics Data System (ADS)

Hondula, David M.; Davis, Robert E.; Knight, David B.; Sitka, Luke J.; Enfield, Kyle; Gawtry, Stephen B.; Stenger, Phillip J.; Deaton, Michael L.; Normile, Caroline P.; Lee, Temple R.

2013-01-01

Respiratory morbidity (particularly COPD and asthma) can be influenced by short-term weather fluctuations that affect air quality and lung function. We developed a model to evaluate meteorological conditions associated with respiratory hospital admissions in the Shenandoah Valley of Virginia, USA. We generated ensembles of classification trees based on six years of respiratory-related hospital admissions (64,620 cases) and a suite of 83 potential environmental predictor variables. As our goal was to identify short-term weather linkages to high admission periods, the dependent variable was formulated as a binary classification of five-day moving average respiratory admission departures from the seasonal mean value. Accounting for seasonality removed the long-term apparent inverse relationship between temperature and admissions. We generated eight total models specific to the northern and southern portions of the valley for each season. All eight models demonstrate predictive skill (mean odds ratio = 3.635) when evaluated using a randomization procedure. The predictor variables selected by the ensembling algorithm vary across models, and both meteorological and air quality variables are included. In general, the models indicate complex linkages between respiratory health and environmental conditions that may be difficult to identify using more traditional approaches.

Human Electro-Muscular Incapacitation (HEMI): Physiological Modeling Weapons

DTIC Science & Technology

The overall goal of this research is to develop a product that estimates the risks of rhabdomyolysis, cardiovascular, and respiratory effects from a...HEMI stimulus under different use scenarios or with different device characteristics. The research and development work outlined in this report cover

Structural identifiability analysis of a cardiovascular system model.

PubMed

Pironet, Antoine; Dauby, Pierre C; Chase, J Geoffrey; Docherty, Paul D; Revie, James A; Desaive, Thomas

2016-05-01

The six-chamber cardiovascular system model of Burkhoff and Tyberg has been used in several theoretical and experimental studies. However, this cardiovascular system model (and others derived from it) are not identifiable from any output set. In this work, two such cases of structural non-identifiability are first presented. These cases occur when the model output set only contains a single type of information (pressure or volume). A specific output set is thus chosen, mixing pressure and volume information and containing only a limited number of clinically available measurements. Then, by manipulating the model equations involving these outputs, it is demonstrated that the six-chamber cardiovascular system model is structurally globally identifiable. A further simplification is made, assuming known cardiac valve resistances. Because of the poor practical identifiability of these four parameters, this assumption is usual. Under this hypothesis, the six-chamber cardiovascular system model is structurally identifiable from an even smaller dataset. As a consequence, parameter values computed from limited but well-chosen datasets are theoretically unique. This means that the parameter identification procedure can safely be performed on the model from such a well-chosen dataset. Thus, the model may be considered suitable for use in diagnosis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

NASA Astrophysics Data System (ADS)

Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

2017-02-01

Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

Modeling respiratory mechanics in the MCAT and spline-based MCAT phantoms

NASA Astrophysics Data System (ADS)

Segars, W. P.; Lalush, D. S.; Tsui, B. M. W.

2001-02-01

Respiratory motion can cause artifacts in myocardial SPECT and computed tomography (CT). The authors incorporate models of respiratory mechanics into the current 4D MCAT and into the next generation spline-based MCAT phantoms. In order to simulate respiratory motion in the current MCAT phantom, the geometric solids for the diaphragm, heart, ribs, and lungs were altered through manipulation of parameters defining them. Affine transformations were applied to the control points defining the same respiratory structures in the spline-based MCAT phantom to simulate respiratory motion. The Non-Uniform Rational B-Spline (NURBS) surfaces for the lungs and body outline were constructed in such a way as to be linked to the surrounding ribs. Expansion and contraction of the thoracic cage then coincided with expansion and contraction of the lungs and body. The changes both phantoms underwent were spline-interpolated over time to create time continuous 4D respiratory models. The authors then used the geometry-based and spline-based MCAT phantoms in an initial simulation study of the effects of respiratory motion on myocardial SPECT. The simulated reconstructed images demonstrated distinct artifacts in the inferior region of the myocardium. It is concluded that both respiratory models can be effective tools for researching effects of respiratory motion.

The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

PubMed

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

2015-04-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

An Improved Dynamic Model for the Respiratory Response to Exercise

PubMed Central

Serna, Leidy Y.; Mañanas, Miguel A.; Hernández, Alher M.; Rabinovich, Roberto A.

2018-01-01

Respiratory system modeling has been extensively studied in steady-state conditions to simulate sleep disorders, to predict its behavior under ventilatory diseases or stimuli and to simulate its interaction with mechanical ventilation. Nevertheless, the studies focused on the instantaneous response are limited, which restricts its application in clinical practice. The aim of this study is double: firstly, to analyze both dynamic and static responses of two known respiratory models under exercise stimuli by using an incremental exercise stimulus sequence (to analyze the model responses when step inputs are applied) and experimental data (to assess prediction capability of each model). Secondly, to propose changes in the models' structures to improve their transient and stationary responses. The versatility of the resulting model vs. the other two is shown according to the ability to simulate ventilatory stimuli, like exercise, with a proper regulation of the arterial blood gases, suitable constant times and a better adjustment to experimental data. The proposed model adjusts the breathing pattern every respiratory cycle using an optimization criterion based on minimization of work of breathing through regulation of respiratory frequency. PMID:29467674

Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis.

PubMed

Berchtold, Joachim F; Constable, Peter D; Smith, Geoffrey W; Mathur, Sheerin M; Morin, Dawn E; Tranquilli, William J

2005-01-01

The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.

Human Adenovirus Associated with Severe Respiratory Infection, Oregon, USA, 2013-2014.

PubMed

Scott, Magdalena Kendall; Chommanard, Christina; Lu, Xiaoyan; Appelgate, Dianna; Grenz, LaDonna; Schneider, Eileen; Gerber, Susan I; Erdman, Dean D; Thomas, Ann

2016-06-01

Several human adenoviruses (HAdVs) can cause respiratory infections, some severe. HAdV-B7, which can cause severe respiratory disease, has not been recently reported in the United States but is reemerging in Asia. During October 2013-July 2014, Oregon health authorities identified 198 persons with respiratory symptoms and an HAdV-positive respiratory tract specimen. Among 136 (69%) hospitalized persons, 31% were admitted to the intensive care unit and 18% required mechanical ventilation; 5 patients died. Molecular typing of 109 specimens showed that most (59%) were HAdV-B7, followed by HAdVs-C1, -C2, -C5 (26%); HAdVs-B3, -B21 (15%); and HAdV-E4 (1%). Molecular analysis of 7 HAdV-B7 isolates identified the virus as genome type d, a strain previously identified only among strains circulating in Asia. Patients with HAdV-B7 were significantly more likely than those without HAdV-B7 to be adults and to have longer hospital stays. HAdV-B7 might be reemerging in the United States, and clinicians should consider HAdV in persons with severe respiratory infection.

Optimization in Cardiovascular Modeling

NASA Astrophysics Data System (ADS)

Marsden, Alison L.

2014-01-01

Fluid mechanics plays a key role in the development, progression, and treatment of cardiovascular disease. Advances in imaging methods and patient-specific modeling now reveal increasingly detailed information about blood flow patterns in health and disease. Building on these tools, there is now an opportunity to couple blood flow simulation with optimization algorithms to improve the design of surgeries and devices, incorporating more information about the flow physics in the design process to augment current medical knowledge. In doing so, a major challenge is the need for efficient optimization tools that are appropriate for unsteady fluid mechanics problems, particularly for the optimization of complex patient-specific models in the presence of uncertainty. This article reviews the state of the art in optimization tools for virtual surgery, device design, and model parameter identification in cardiovascular flow and mechanobiology applications. In particular, it reviews trade-offs between traditional gradient-based methods and derivative-free approaches, as well as the need to incorporate uncertainties. Key future challenges are outlined, which extend to the incorporation of biological response and the customization of surgeries and devices for individual patients.

Assessing the effects of pharmacological agents on respiratory dynamics using time-series modeling.

PubMed

Wong, Kin Foon Kevin; Gong, Jen J; Cotten, Joseph F; Solt, Ken; Brown, Emery N

2013-04-01

Developing quantitative descriptions of how stimulant and depressant drugs affect the respiratory system is an important focus in medical research. Respiratory variables-respiratory rate, tidal volume, and end tidal carbon dioxide-have prominent temporal dynamics that make it inappropriate to use standard hypothesis-testing methods that assume independent observations to assess the effects of these pharmacological agents. We present a polynomial signal plus autoregressive noise model for analysis of continuously recorded respiratory variables. We use a cyclic descent algorithm to maximize the conditional log likelihood of the parameters and the corrected Akaike's information criterion to choose simultaneously the orders of the polynomial and the autoregressive models. In an analysis of respiratory rates recorded from anesthetized rats before and after administration of the respiratory stimulant methylphenidate, we use the model to construct within-animal z-tests of the drug effect that take account of the time-varying nature of the mean respiratory rate and the serial dependence in rate measurements. We correct for the effect of model lack-of-fit on our inferences by also computing bootstrap confidence intervals for the average difference in respiratory rate pre- and postmethylphenidate treatment. Our time-series modeling quantifies within each animal the substantial increase in mean respiratory rate and respiratory dynamics following methylphenidate administration. This paradigm can be readily adapted to analyze the dynamics of other respiratory variables before and after pharmacologic treatments.

Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

PubMed

Portelli, J; Gordon, A; May, J T

1998-11-01

The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling.

PubMed

Zieliński, Łukasz P; Smith, Anthony C; Smith, Alexander G; Robinson, Alan J

2016-11-01

Mitochondrial respiratory chain dysfunction causes a variety of life-threatening diseases affecting about 1 in 4300 adults. These diseases are genetically heterogeneous, but have the same outcome; reduced activity of mitochondrial respiratory chain complexes causing decreased ATP production and potentially toxic accumulation of metabolites. Severity and tissue specificity of these effects varies between patients by unknown mechanisms and treatment options are limited. So far most research has focused on the complexes themselves, and the impact on overall cellular metabolism is largely unclear. To illustrate how computer modelling can be used to better understand the potential impact of these disorders and inspire new research directions and treatments, we simulated them using a computer model of human cardiomyocyte mitochondrial metabolism containing over 300 characterised reactions and transport steps with experimental parameters taken from the literature. Overall, simulations were consistent with patient symptoms, supporting their biological and medical significance. These simulations predicted: complex I deficiencies could be compensated using multiple pathways; complex II deficiencies had less metabolic flexibility due to impacting both the TCA cycle and the respiratory chain; and complex III and IV deficiencies caused greatest decreases in ATP production with metabolic consequences that parallel hypoxia. Our study demonstrates how results from computer models can be compared to a clinical phenotype and used as a tool for hypothesis generation for subsequent experimental testing. These simulations can enhance understanding of dysfunctional mitochondrial metabolism and suggest new avenues for research into treatment of mitochondrial disease and other areas of mitochondrial dysfunction. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Surfactant Protein D in Respiratory and Non-Respiratory Diseases

PubMed Central

Sorensen, Grith L.

2018-01-01

Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia. SP-D exerts antimicrobial effects and dampens inflammation through direct microbial interactions and modulation of host cell responses via a series of cellular receptors. However, low protein concentrations, genetic variation, biochemical modification, and proteolytic breakdown can induce decomposition of multimeric SP-D into low-molecular weight forms, which may induce pro-inflammatory SP-D signaling. Multimeric SP-D can decompose into trimeric SP-D, and this process, and total SP-D levels, are partly determined by variation within the SP-D gene, SFTPD. SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease. Disease-induced breakdown or modifications of SP-D facilitate its systemic leakage from the lung, and circulatory SP-D is a promising biomarker for lung injury. Moreover, studies in preclinical animal models have demonstrated that local pulmonary treatment with recombinant SP-D is beneficial in these diseases. In recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory effects in various non-pulmonary organs and to have effects on lipid metabolism and pro-inflammatory effects in vessel walls, which enhance the risk of atherosclerosis. A common SFTPD polymorphism is associated with atherosclerosis and diabetes, and SP-D has been associated with metabolic disorders because of its effects in the endothelium and adipocytes and its obesity-dampening properties. This review summarizes and discusses the reported genetic associations of SP-D with disease and the clinical utility of circulating SP-D for respiratory disease prognosis. Moreover, basic research on the mechanistic links between SP-D and respiratory, cardiovascular, and metabolic diseases

Nonlinear dynamics of cardiovascular ageing

PubMed Central

Shiogai, Y.; Stefanovska, A.; McClintock, P.V.E.

2010-01-01

The application of methods drawn from nonlinear and stochastic dynamics to the analysis of cardiovascular time series is reviewed, with particular reference to the identification of changes associated with ageing. The natural variability of the heart rate (HRV) is considered in detail, including the respiratory sinus arrhythmia (RSA) corresponding to modulation of the instantaneous cardiac frequency by the rhythm of respiration. HRV has been intensively studied using traditional spectral analyses, e.g. by Fourier transform or autoregressive methods, and, because of its complexity, has been used as a paradigm for testing several proposed new methods of complexity analysis. These methods are reviewed. The application of time–frequency methods to HRV is considered, including in particular the wavelet transform which can resolve the time-dependent spectral content of HRV. Attention is focused on the cardio-respiratory interaction by introduction of the respiratory frequency variability signal (RFV), which can be acquired simultaneously with HRV by use of a respiratory effort transducer. Current methods for the analysis of interacting oscillators are reviewed and applied to cardio-respiratory data, including those for the quantification of synchronization and direction of coupling. These reveal the effect of ageing on the cardio-respiratory interaction through changes in the mutual modulation of the instantaneous cardiac and respiratory frequencies. Analyses of blood flow signals recorded with laser Doppler flowmetry are reviewed and related to the current understanding of how endothelial-dependent oscillations evolve with age: the inner lining of the vessels (the endothelium) is shown to be of crucial importance to the emerging picture. It is concluded that analyses of the complex and nonlinear dynamics of the cardiovascular system can illuminate the mechanisms of blood circulation, and that the heart, the lungs and the vascular system function as a single entity in

Nonlinear dynamics of cardiovascular ageing

NASA Astrophysics Data System (ADS)

Shiogai, Y.; Stefanovska, A.; McClintock, P. V. E.

2010-03-01

The application of methods drawn from nonlinear and stochastic dynamics to the analysis of cardiovascular time series is reviewed, with particular reference to the identification of changes associated with ageing. The natural variability of the heart rate (HRV) is considered in detail, including the respiratory sinus arrhythmia (RSA) corresponding to modulation of the instantaneous cardiac frequency by the rhythm of respiration. HRV has been intensively studied using traditional spectral analyses, e.g. by Fourier transform or autoregressive methods, and, because of its complexity, has been used as a paradigm for testing several proposed new methods of complexity analysis. These methods are reviewed. The application of time-frequency methods to HRV is considered, including in particular the wavelet transform which can resolve the time-dependent spectral content of HRV. Attention is focused on the cardio-respiratory interaction by introduction of the respiratory frequency variability signal (RFV), which can be acquired simultaneously with HRV by use of a respiratory effort transducer. Current methods for the analysis of interacting oscillators are reviewed and applied to cardio-respiratory data, including those for the quantification of synchronization and direction of coupling. These reveal the effect of ageing on the cardio-respiratory interaction through changes in the mutual modulation of the instantaneous cardiac and respiratory frequencies. Analyses of blood flow signals recorded with laser Doppler flowmetry are reviewed and related to the current understanding of how endothelial-dependent oscillations evolve with age: the inner lining of the vessels (the endothelium) is shown to be of crucial importance to the emerging picture. It is concluded that analyses of the complex and nonlinear dynamics of the cardiovascular system can illuminate the mechanisms of blood circulation, and that the heart, the lungs and the vascular system function as a single entity in

Introduction: Cardiovascular physics

NASA Astrophysics Data System (ADS)

Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert

2007-03-01

The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.

Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction

PubMed Central

Omrani, Ali S.; Al-Tawfiq, Jaffar A.

2015-01-01

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine. PMID:26924345

A plausible radiobiological model of cardiovascular disease at low or fractionated doses

NASA Astrophysics Data System (ADS)

Little, Mark; Vandoolaeghe, Wendy; Gola, Anna; Tzoulaki, Ioanna

Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally-exposed groups receiving small daily radia-tion doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis, and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1) concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and can-cer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapo-lation would be appropriate for this endpoint.

Design of a new artificial breathing system for simulating the human respiratory activities.

PubMed

Essoukaki, Elmaati; Rattal, Mourad; Ben Taleb, Lhoucine; Harmouchi, Mohammed; Assir, Abdelhadi; Mouhsen, Azeddine; Lyazidi, Aissam

2018-01-01

The purpose of this work is the conception and implementation of an artificial active respiratory system that allows the simulation of human respiratory activities. The system consists of two modules, mechanical and electronical. The first one represents a cylindrical lung adjustable in resistance and compliance. This lung is located inside a transparent thoracic box, connected to a piston that generates variable respiratory efforts. The parameters of the system, which are pressure, flow and volume, are measured by the second module. A computer application was developed to control the whole system, and enables the display of the parameters. A series of tests were made to evaluate the respiratory efforts, resistances and compliances. The results were compared to the bibliographical studies, allowing the validation of the proposed system.

Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.

PubMed

Macchiaverni, P; Rekima, A; Turfkruyer, M; Mascarell, L; Airouche, S; Moingeon, P; Adel-Patient, K; Condino-Neto, A; Annesi-Maesano, I; Prescott, S L; Tulic, M K; Verhasselt, V

2014-03-01

There is an urgent need to identify environmental risk and protective factors in early life for the prevention of allergy. Our study demonstrates the presence of respiratory allergen from house dust mite, Der p 1, in human breast milk. Der p 1 in milk is immunoreactive, present in similar amounts as dietary egg antigen, and can be found in breast milk from diverse regions of the world. In a mouse model of asthma, oral exposure to Der p through breast milk strongly promotes sensitization rather than protect the progeny as we reported with egg antigen. These data highlight that antigen administration to the neonate through the oral route may contribute to child allergic sensitization and have important implications for the design of studies assessing early oral antigen exposure for allergic disease prevention. The up-to-now unknown worldwide presence of respiratory allergen in maternal milk allows new interpretation and design of environmental control epidemiological studies for allergic disease prevention. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modeling static and dynamic human cardiovascular responses to exercise.

PubMed

Stremel, R W; Bernauer, E M; Harter, L W; Schultz, R A; Walters, R F

1975-08-01

A human performance model has been developed and described [9] which portrays the human circulatory, thermo regulatory and energy-exchange systems as an intercoupled set. In this model, steady state or static relationships are used to describe oxygen consumption and blood flow. For example, heart rate (HTRT) is calculated as a function of the oxygen and the thermo-regulatory requirements of each body compartment, using the steady state work values of cardiac output (CO, sum of all compartment blood flows) and stroke volume (SV, assumed maximal after 40% maximal oxygen consumption): HTRT=CO/SV. The steady state model has proven to be an acceptable first approximation, but the inclusion of transient characteristics are essential in describing the overall systems' adjustment to exercise stress. In the present study, the dynamic transient characteristics of heart rate, stroke volume and cardiac output were obtained from experiments utilizing step and sinusoidal forcing of work. The gain and phase relationships reveal a probable first order system with a six minute time constant, and are utilized to model the transient characteristics of these parameters. This approach leads to a more complex model but a more accurate representation of the physiology involved. The instrumentation and programming essential to these experiments are described.

Air pollution and cardiovascular and respiratory disease: Rationale and methodology of CAPACITY study.

PubMed

Rabiei, Katayoun; Hosseini, Sayed Mohsen; Sadeghi, Erfan; Jafari-Koshki, Tohid; Rahimi, Mojtaba; Shishehforoush, Mansour; Lahijanzadeh, Ahmadreza; Sadeghian, Babak; Moazam, Elham; Mohebi, Mohammad Bagher; Ezatian, Victoria; Sarrafzadegan, Nizal

2017-11-01

Considering the high level of air pollution and its impact on health, we aimed to study the correlation of air pollution with hospitalization and mortality of cardiovascular (CVD) and respiratory diseases (ResD) (CAPACITY) to determine the effects of air pollutants on CVD and ResD hospitalizations and deaths in Isfahan, Iran. Hourly levels of air pollutants including particulate matter (PM), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3), information of CVD and ResD admissions and death certificate were obtained respectively from Department of Environment (DOE), Iran, hospitals and cemetery. Time series and case-crossover model were used to find the impact of air pollutants. This paper only summarizes the descriptive findings of the CAPACITY study. The total number of hospitalized patients were 23781 in 2010 and 22485 in 2011. The most frequent cause of hospitalization and death was ischemic heart diseases in both years. While the mean annual levels of O3, CO, and PM10 were lower in 2011 than in 2010, NO2 and SO2 levels higher in 2011. In both years, PM10 was similarly increased during last month of fall, late spring and early summer. In 2011, the PM2.5 and PM10 monthly trend of change were similar. The CAPACITY study is one of the few large-scale studies that evaluated the effects of air pollutants on a variety of CVD and ResD in a large city of Iran. This study can provide many findings that could clarify the effects of these pollutants on the incidence and burden of both disease groups.

Air pollution and cardiovascular and respiratory disease: Rationale and methodology of CAPACITY study

PubMed Central

Rabiei, Katayoun; Hosseini, Sayed Mohsen; Sadeghi, Erfan; Jafari-Koshki, Tohid; Rahimi, Mojtaba; Shishehforoush, Mansour; Lahijanzadeh, Ahmadreza; Sadeghian, Babak; Moazam, Elham; Mohebi, Mohammad Bagher; Ezatian, Victoria; Sarrafzadegan, Nizal

2017-01-01

BACKGROUND Considering the high level of air pollution and its impact on health, we aimed to study the correlation of air pollution with hospitalization and mortality of cardiovascular (CVD) and respiratory diseases (ResD) (CAPACITY) to determine the effects of air pollutants on CVD and ResD hospitalizations and deaths in Isfahan, Iran. METHODS Hourly levels of air pollutants including particulate matter (PM), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3), information of CVD and ResD admissions and death certificate were obtained respectively from Department of Environment (DOE), Iran, hospitals and cemetery. Time series and case-crossover model were used to find the impact of air pollutants. This paper only summarizes the descriptive findings of the CAPACITY study. RESULTS The total number of hospitalized patients were 23781 in 2010 and 22485 in 2011. The most frequent cause of hospitalization and death was ischemic heart diseases in both years. While the mean annual levels of O3, CO, and PM10 were lower in 2011 than in 2010, NO2 and SO2 levels higher in 2011. In both years, PM10 was similarly increased during last month of fall, late spring and early summer. In 2011, the PM2.5 and PM10 monthly trend of change were similar. CONCLUSION The CAPACITY study is one of the few large-scale studies that evaluated the effects of air pollutants on a variety of CVD and ResD in a large city of Iran. This study can provide many findings that could clarify the effects of these pollutants on the incidence and burden of both disease groups. PMID:29643921

Detection of severe respiratory disease epidemic outbreaks by CUSUM-based overcrowd-severe-respiratory-disease-index model.

PubMed

Polanco, Carlos; Castañón-González, Jorge Alberto; Macías, Alejandro E; Samaniego, José Lino; Buhse, Thomas; Villanueva-Martínez, Sebastián

2013-01-01

A severe respiratory disease epidemic outbreak correlates with a high demand of specific supplies and specialized personnel to hold it back in a wide region or set of regions; these supplies would be beds, storage areas, hemodynamic monitors, and mechanical ventilators, as well as physicians, respiratory technicians, and specialized nurses. We describe an online cumulative sum based model named Overcrowd-Severe-Respiratory-Disease-Index based on the Modified Overcrowd Index that simultaneously monitors and informs the demand of those supplies and personnel in a healthcare network generating early warnings of severe respiratory disease epidemic outbreaks through the interpretation of such variables. A post hoc historical archive is generated, helping physicians in charge to improve the transit and future allocation of supplies in the entire hospital network during the outbreak. The model was thoroughly verified in a virtual scenario, generating multiple epidemic outbreaks in a 6-year span for a 13-hospital network. When it was superimposed over the H1N1 influenza outbreak census (2008-2010) taken by the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, it showed that it is an effective algorithm to notify early warnings of severe respiratory disease epidemic outbreaks with a minimal rate of false alerts.

Detection of Severe Respiratory Disease Epidemic Outbreaks by CUSUM-Based Overcrowd-Severe-Respiratory-Disease-Index Model

PubMed Central

Castañón-González, Jorge Alberto; Macías, Alejandro E.; Samaniego, José Lino; Buhse, Thomas; Villanueva-Martínez, Sebastián

2013-01-01

A severe respiratory disease epidemic outbreak correlates with a high demand of specific supplies and specialized personnel to hold it back in a wide region or set of regions; these supplies would be beds, storage areas, hemodynamic monitors, and mechanical ventilators, as well as physicians, respiratory technicians, and specialized nurses. We describe an online cumulative sum based model named Overcrowd-Severe-Respiratory-Disease-Index based on the Modified Overcrowd Index that simultaneously monitors and informs the demand of those supplies and personnel in a healthcare network generating early warnings of severe respiratory disease epidemic outbreaks through the interpretation of such variables. A post hoc historical archive is generated, helping physicians in charge to improve the transit and future allocation of supplies in the entire hospital network during the outbreak. The model was thoroughly verified in a virtual scenario, generating multiple epidemic outbreaks in a 6-year span for a 13-hospital network. When it was superimposed over the H1N1 influenza outbreak census (2008–2010) taken by the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, it showed that it is an effective algorithm to notify early warnings of severe respiratory disease epidemic outbreaks with a minimal rate of false alerts. PMID:24069063

A Nano-Thin Film-Based Prototype QCM Sensor Array for Monitoring Human Breath and Respiratory Patterns.

PubMed

Selyanchyn, Roman; Wakamatsu, Shunichi; Hayashi, Kenshi; Lee, Seung-Woo

2015-07-31

Quartz crystal microbalance (QCM) sensor array was developed for multi-purpose human respiration assessment. The sensor system was designed to provide feedback for human respiration. Thorough optimization of measurement conditions: air flow, temperature in the QCM chamber, frequency measurement rate, and electrode position regarding to the gas flow-was performed. As shown, acquisition of respiratory parameters (rate and respiratory pattern) could be achieved even with a single electrode used in the system. The prototype system contains eight available QCM channels that can be potentially used for selective responses to certain breath chemicals. At present, the prototype machine is ready for the assessment of respiratory functions in larger populations in order to gain statistical validation. To the best of our knowledge, the developed prototype is the only respiratory assessment system based on surface modified QCM sensors.

Acute and delayed effects of intermittant ozone on cardiovascular and thermoregulatory responses of young and aged rats

EPA Science Inventory

Ozone (03) is associated with cardiovascular and respiratory diseases. The aged population is considered to be more sensitive to air pollutants but relatively few studies have demonstrated increased susceptibility in animal models of aging. To study the acute and delayed physiolo...

Computer model of cardiovascular control system responses to exercise

NASA Technical Reports Server (NTRS)

Croston, R. C.; Rummel, J. A.; Kay, F. J.

1973-01-01

Approaches of systems analysis and mathematical modeling together with computer simulation techniques are applied to the cardiovascular system in order to simulate dynamic responses of the system to a range of exercise work loads. A block diagram of the circulatory model is presented, taking into account arterial segments, venous segments, arterio-venous circulation branches, and the heart. A cardiovascular control system model is also discussed together with model test results.

The impact of PM2.5 on the human respiratory system.

PubMed

Xing, Yu-Fei; Xu, Yue-Hua; Shi, Min-Hua; Lian, Yi-Xin

2016-01-01

Recently, many researchers paid more attentions to the association between air pollution and respiratory system disease. In the past few years, levels of smog have increased throughout China resulting in the deterioration of air quality, raising worldwide concerns. PM2.5 (particles less than 2.5 micrometers in diameter) can penetrate deeply into the lung, irritate and corrode the alveolar wall, and consequently impair lung function. Hence it is important to investigate the impact of PM2.5 on the respiratory system and then to help China combat the current air pollution problems. In this review, we will discuss PM2.5 damage on human respiratory system from epidemiological, experimental and mechanism studies. At last, we recommend to the population to limit exposure to air pollution and call to the authorities to create an index of pollution related to health.

Dynamic Coupling Between Respiratory and Cardiovascular System

NASA Astrophysics Data System (ADS)

Censi, Federica; Calcagnini, Giovanni; Cerutti, Sergio

The analysis of non-linear dynamics of the coupling among interacting quantities can be very useful for understanding the cardiorespiratory and cardiovascular control mechanisms. In this chapter RP is used to detect and quantify the degree of non-linear coupling between respiration and spontaneous rhythms of both heart rate and blood pressure variability signals. RQA turned out to be suitable for a quantitative evaluation of the observed coupling patterns among rhythms, both in simulated and real data, providing different degrees of coupling. The results from the simulated data showed that the increased degree of coupling between the signals was marked by the increase of PR and PD, and by the decrease of ER. When the RQA was applied to experimental data, PD and ER turned out to be the most significant variables, compared to PR. A remarkable finding is the detection of transient 1:2 PL episodes between respiration and cardiovascular variability signals. This phenomenon can be associated to a sub-harmonic synchronization between the two main rhythms of HR and BP variability series.

Respiratory system

NASA Technical Reports Server (NTRS)

Bartlett, R. G., Jr.

1973-01-01

The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.

An interactive videogame designed to improve respiratory navigator efficiency in children undergoing cardiovascular magnetic resonance.

PubMed

Hamlet, Sean M; Haggerty, Christopher M; Suever, Jonathan D; Wehner, Gregory J; Grabau, Jonathan D; Andres, Kristin N; Vandsburger, Moriel H; Powell, David K; Sorrell, Vincent L; Fornwalt, Brandon K

2016-09-06

Advanced cardiovascular magnetic resonance (CMR) acquisitions often require long scan durations that necessitate respiratory navigator gating. The tradeoff of navigator gating is reduced scan efficiency, particularly when the patient's breathing patterns are inconsistent, as is commonly seen in children. We hypothesized that engaging pediatric participants with a navigator-controlled videogame to help control breathing patterns would improve navigator efficiency and maintain image quality. We developed custom software that processed the Siemens respiratory navigator image in real-time during CMR and represented diaphragm position using a cartoon avatar, which was projected to the participant in the scanner as visual feedback. The game incentivized children to breathe such that the avatar was positioned within the navigator acceptance window (±3 mm) throughout image acquisition. Using a 3T Siemens Tim Trio, 50 children (Age: 14 ± 3 years, 48 % female) with no significant past medical history underwent a respiratory navigator-gated 2D spiral cine displacement encoding with stimulated echoes (DENSE) CMR acquisition first with no feedback (NF) and then with the feedback game (FG). Thirty of the 50 children were randomized to undergo extensive off-scanner training with the FG using a MRI simulator, or no off-scanner training. Navigator efficiency, signal-to-noise ratio (SNR), and global left-ventricular strains were determined for each participant and compared. Using the FG improved average navigator efficiency from 33 ± 15 to 58 ± 13 % (p < 0.001) and improved SNR by 5 % (p = 0.01) compared to acquisitions with NF. There was no difference in navigator efficiency (p = 0.90) or SNR (p = 0.77) between untrained and trained participants for FG acquisitions. Circumferential and radial strains derived from FG acquisitions were slightly reduced compared to NF acquisitions (-16 ± 2 % vs -17 ± 2 %, p < 0.001; 40 ± 10�

CO2 exposure as translational cross-species experimental model for panic.

PubMed

Leibold, N K; van den Hove, D L A; Viechtbauer, W; Buchanan, G F; Goossens, L; Lange, I; Knuts, I; Lesch, K P; Steinbusch, H W M; Schruers, K R J

2016-09-06

The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral-emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.

NASAL-Geom, a free upper respiratory tract 3D model reconstruction software

NASA Astrophysics Data System (ADS)

Cercos-Pita, J. L.; Cal, I. R.; Duque, D.; de Moreta, G. Sanjuán

2018-02-01

The tool NASAL-Geom, a free upper respiratory tract 3D model reconstruction software, is here described. As a free software, researchers and professionals are welcome to obtain, analyze, improve and redistribute it, potentially increasing the rate of development, and reducing at the same time ethical conflicts regarding medical applications which cannot be analyzed. Additionally, the tool has been optimized for the specific task of reading upper respiratory tract Computerized Tomography scans, and producing 3D geometries. The reconstruction process is divided into three stages: preprocessing (including Metal Artifact Reduction, noise removal, and feature enhancement), segmentation (where the nasal cavity is identified), and 3D geometry reconstruction. The tool has been automatized (i.e. no human intervention is required) a critical feature to avoid bias in the reconstructed geometries. The applied methodology is discussed, as well as the program robustness and precision.

LOWER RESPIRATORY TRACT STRUCTURE OF LABORATORY ANIMALS AND HUMANS: DOSIMETRY IMPLICATIONS

EPA Science Inventory

Significant differences in lower respiratory tract structure exist both within an animal and between species at each level of anatomy. rregular bipodial and tripodial branching patterns of airways are present in human an nonhuman primate lungs. n contrast, the dog and common labo...

Breathlessness, fatigue and the respiratory muscles.

PubMed

Mioxham, John; Jolley, Caroline

2009-10-01

Breathlessness is a common symptom in respiratory, cardiovascular and malignant disease. It reduces exercise tolerance and mobility, and is an important determinant of quality of life. The multifactorial nature of the symptom often presents difficulties in understanding why individual patients are breathless, and how breathlessness should best be palliated, especially in advanced disease. However, insights into the neurophysiological factors underlying the symptom can be gained by considering the balance between the load on, and capacity of, the respiratory muscles and increased neural respiratory drive, reflecting increased respiratory effort. Mismatch between efferent neural respiratory drive and afferent feedback, reflecting the degree of neuromechanical dissociation, is also important. This paper describes mechanisms by which ventilatory load, capacity and drive may be affected by disease, and how these can be measured physiologically. The schema presented also provides a framework for understanding the mechanisms by which interventions that relieve breathlessness may have their effect.

[Detection of human papillomavirus in the upper respiratory tract in children without recurrent respiratory papillomatosis].

PubMed

Sun, Yue-feng; Wu, Yi-dong; Wu, Lei; Jiang, Juan-juan; Gao, Rong; Xu, Bin; Chen, Xiao-wei; Zhao, Zheng-yan

2012-12-01

The purpose of this prospective study was to investigate the presence of human papillomavirus (HPV) in tonsillectomy and adenoidectomy specimens from pediatric patients without juvenile-onset recurrent respiratory papillomatosis (JORRP), so as to understand the effect of HPV infection in the upper respiratory tract in children. Two hundred and forty-one pediatric patients without known JORRP or other HPV-related diseases undergoing tonsillectomy and/or adenoidectomy for hypertrophy or chronic tonsillitis were enrolled in this prospective study. One hundred and seventy-seven fresh samples of tonsillar tissues and 195 samples of adenoid tissues were collected and then examined for the presence of HPV DNA with the polymerase chain reaction (PCR) technique and typing. Laryngeal papilloma specimens from 17 patients obtained during routine debulking procedures were also analyzed and served as positive controls. All 17 papilloma specimens were positive for HPV DNA and the type was 6 or 11. This result confirmed that the methods used were valid for detecting HPV infection. HPV DNA was detected in 2 of the 177 tonsillar specimens and zero of the 195 adenoid specimens. The two positive samples were confirmed with typing. One was positive for HPV6 and the other for HPV11. Review of the medical records of these two cases confirmed that there were no history of HPV-related diseases. Histologic analysis of their specimens showed lymphoid hyperplasia, no specific changes suggesting HPV infection and no signs of malignancy. The HPV infection rate in upper respiratory tract was 0.8% (2/241). There is HPV infection in upper respiratory tract in Chinese children without JORRP, but maybe is not sufficient for the formation of JORRP.

The physiological effects of slow breathing in the healthy human

PubMed Central

Russo, Marc A.; Santarelli, Danielle M.; O’Rourke, Dean

2017-01-01

Slow breathing practices have been adopted in the modern world across the globe due to their claimed health benefits. This has piqued the interest of researchers and clinicians who have initiated investigations into the physiological (and psychological) effects of slow breathing techniques and attempted to uncover the underlying mechanisms. The aim of this article is to provide a comprehensive overview of normal respiratory physiology and the documented physiological effects of slow breathing techniques according to research in healthy humans. The review focuses on the physiological implications to the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, with particular focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate variability, cardiorespiratory coupling, respiratory sinus arrhythmia and sympathovagal balance. The review ends with a brief discussion of the potential clinical implications of slow breathing techniques. This is a topic that warrants further research, understanding and discussion. Key points Slow breathing practices have gained popularity in the western world due to their claimed health benefits, yet remain relatively untouched by the medical community. Investigations into the physiological effects of slow breathing have uncovered significant effects on the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems. Key findings include effects on respiratory muscle activity, ventilation efficiency, chemoreflex and baroreflex sensitivity, heart rate variability, blood flow dynamics, respiratory sinus arrhythmia, cardiorespiratory coupling, and sympathovagal balance. There appears to be potential for use of controlled slow breathing techniques as a means of optimising physiological parameters that appear to be associated with health and longevity, and that may extend to disease states; however, there is a dire need for further research into the area. Educational aims To provide

Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human

PubMed Central

Song, Huai-Dong; Tu, Chang-Chun; Zhang, Guo-Wei; Wang, Sheng-Yue; Zheng, Kui; Lei, Lian-Cheng; Chen, Qiu-Xia; Gao, Yu-Wei; Zhou, Hui-Qiong; Xiang, Hua; Zheng, Hua-Jun; Chern, Shur-Wern Wang; Cheng, Feng; Pan, Chun-Ming; Xuan, Hua; Chen, Sai-Juan; Luo, Hui-Ming; Zhou, Duan-Hua; Liu, Yu-Fei; He, Jian-Feng; Qin, Peng-Zhe; Li, Ling-Hui; Ren, Yu-Qi; Liang, Wen-Jia; Yu, Ye-Dong; Anderson, Larry; Wang, Ming; Xu, Rui-Heng; Wu, Xin-Wei; Zheng, Huan-Ying; Chen, Jin-Ding; Liang, Guodong; Gao, Yang; Liao, Ming; Fang, Ling; Jiang, Li-Yun; Li, Hui; Chen, Fang; Di, Biao; He, Li-Juan; Lin, Jin-Yan; Tong, Suxiang; Kong, Xiangang; Du, Lin; Hao, Pei; Tang, Hua; Bernini, Andrea; Yu, Xiao-Jing; Spiga, Ottavia; Guo, Zong-Ming; Pan, Hai-Yan; He, Wei-Zhong; Manuguerra, Jean-Claude; Fontanet, Arnaud; Danchin, Antoine; Niccolai, Neri; Li, Yi-Xue; Wu, Chung-I; Zhao, Guo-Ping

2005-01-01

The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003. PMID:15695582

A Nano-Thin Film-Based Prototype QCM Sensor Array for Monitoring Human Breath and Respiratory Patterns

PubMed Central

Selyanchyn, Roman; Wakamatsu, Shunichi; Hayashi, Kenshi; Lee, Seung-Woo

2015-01-01

Quartz crystal microbalance (QCM) sensor array was developed for multi-purpose human respiration assessment. The sensor system was designed to provide feedback for human respiration. Thorough optimization of measurement conditions: air flow, temperature in the QCM chamber, frequency measurement rate, and electrode position regarding to the gas flow—was performed. As shown, acquisition of respiratory parameters (rate and respiratory pattern) could be achieved even with a single electrode used in the system. The prototype system contains eight available QCM channels that can be potentially used for selective responses to certain breath chemicals. At present, the prototype machine is ready for the assessment of respiratory functions in larger populations in order to gain statistical validation. To the best of our knowledge, the developed prototype is the only respiratory assessment system based on surface modified QCM sensors. PMID:26263994

Modeling acute respiratory illness during the 2007 San Diego wildland fires using a coupled emissions-transport system and generalized additive modeling.

PubMed

Thelen, Brian; French, Nancy H F; Koziol, Benjamin W; Billmire, Michael; Owen, Robert Chris; Johnson, Jeffrey; Ginsberg, Michele; Loboda, Tatiana; Wu, Shiliang

2013-11-05

A study of the impacts on respiratory health of the 2007 wildland fires in and around San Diego County, California is presented. This study helps to address the impact of fire emissions on human health by modeling the exposure potential of proximate populations to atmospheric particulate matter (PM) from vegetation fires. Currently, there is no standard methodology to model and forecast the potential respiratory health effects of PM plumes from wildland fires, and in part this is due to a lack of methodology for rigorously relating the two. The contribution in this research specifically targets that absence by modeling explicitly the emission, transmission, and distribution of PM following a wildland fire in both space and time. Coupled empirical and deterministic models describing particulate matter (PM) emissions and atmospheric dispersion were linked to spatially explicit syndromic surveillance health data records collected through the San Diego Aberration Detection and Incident Characterization (SDADIC) system using a Generalized Additive Modeling (GAM) statistical approach. Two levels of geographic aggregation were modeled, a county-wide regional level and division of the county into six sub regions. Selected health syndromes within SDADIC from 16 emergency departments within San Diego County relevant for respiratory health were identified for inclusion in the model. The model captured the variability in emergency department visits due to several factors by including nine ancillary variables in addition to wildfire PM concentration. The model coefficients and nonlinear function plots indicate that at peak fire PM concentrations the odds of a person seeking emergency care is increased by approximately 50% compared to non-fire conditions (40% for the regional case, 70% for a geographically specific case). The sub-regional analyses show that demographic variables also influence respiratory health outcomes from smoke. The model developed in this study allows a

Modeling acute respiratory illness during the 2007 San Diego wildland fires using a coupled emissions-transport system and generalized additive modeling

PubMed Central

2013-01-01

Background A study of the impacts on respiratory health of the 2007 wildland fires in and around San Diego County, California is presented. This study helps to address the impact of fire emissions on human health by modeling the exposure potential of proximate populations to atmospheric particulate matter (PM) from vegetation fires. Currently, there is no standard methodology to model and forecast the potential respiratory health effects of PM plumes from wildland fires, and in part this is due to a lack of methodology for rigorously relating the two. The contribution in this research specifically targets that absence by modeling explicitly the emission, transmission, and distribution of PM following a wildland fire in both space and time. Methods Coupled empirical and deterministic models describing particulate matter (PM) emissions and atmospheric dispersion were linked to spatially explicit syndromic surveillance health data records collected through the San Diego Aberration Detection and Incident Characterization (SDADIC) system using a Generalized Additive Modeling (GAM) statistical approach. Two levels of geographic aggregation were modeled, a county-wide regional level and division of the county into six sub regions. Selected health syndromes within SDADIC from 16 emergency departments within San Diego County relevant for respiratory health were identified for inclusion in the model. Results The model captured the variability in emergency department visits due to several factors by including nine ancillary variables in addition to wildfire PM concentration. The model coefficients and nonlinear function plots indicate that at peak fire PM concentrations the odds of a person seeking emergency care is increased by approximately 50% compared to non-fire conditions (40% for the regional case, 70% for a geographically specific case). The sub-regional analyses show that demographic variables also influence respiratory health outcomes from smoke. Conclusions The

Interdisciplinary Approaches of Transcranial Magnetic Stimulation Applied to a Respiratory Neuronal Circuitry Model

PubMed Central

Vinit, Stéphane; Keomani, Emilie; Deramaudt, Thérèse B.; Spruance, Victoria M.; Bezdudnaya, Tatiana; Lane, Michael A.

2014-01-01

Respiratory related diseases associated with the neuronal control of breathing represent life-threatening issues and to date, no effective therapeutics are available to enhance the impaired function. The aim of this study was to determine whether a preclinical respiratory model could be used for further studies to develop a non-invasive therapeutic tool applied to rat diaphragmatic neuronal circuitry. Transcranial magnetic stimulation (TMS) was performed on adult male Sprague-Dawley rats using a human figure-of-eight coil. The largest diaphragmatic motor evoked potentials (MEPdia) were recorded when the center of the coil was positioned 6 mm caudal from Bregma, involving a stimulation of respiratory supraspinal pathways. Magnetic shielding of the coil with mu metal reduced magnetic field intensities and improved focality with increased motor threshold and lower amplitude recruitment curve. Moreover, transynaptic neuroanatomical tracing with pseudorabies virus (applied to the diaphragm) suggest that connections exist between the motor cortex, the periaqueductal grey cell regions, several brainstem neurons and spinal phrenic motoneurons (distributed in the C3-4 spinal cord). These results reveal the anatomical substrate through which supraspinal stimulation can convey descending action potential volleys to the spinal motoneurons (directly or indirectly). We conclude that MEPdia following a single pulse of TMS can be successfully recorded in the rat and may be used in the assessment of respiratory supraspinal plasticity. Supraspinal non-invasive stimulations aimed to neuromodulate respiratory circuitry will enable new avenues of research into neuroplasticity and the development of therapies for respiratory dysfunction associated with neural injury and disease (e.g. spinal cord injury, amyotrophic lateral sclerosis). PMID:25406091

[Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

PubMed

Chen, Y S; Lin, X H; Li, H R; Hua, Z D; Lin, M Q; Huang, W S; Yu, T; Lyu, H Y; Mao, W P; Liang, Y Q; Peng, X R; Chen, S J; Zheng, H; Lian, S Q; Hu, X L; Yao, X Q

2017-12-12

Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the

Characterization of Nipah virus infection in a model of human airway epithelial cells cultured at an air-liquid interface.

PubMed

Escaffre, Olivier; Borisevich, Viktoriya; Vergara, Leoncio A; Wen, Julie W; Long, Dan; Rockx, Barry

2016-05-01

Nipah virus (NiV) is an emerging paramyxovirus that can cause lethal respiratory illness in humans. No vaccine/therapeutic is currently licensed for humans. Human-to-human transmission was previously reported during outbreaks and NiV could be isolated from respiratory secretions, but the proportion of cases in Malaysia exhibiting respiratory symptoms was significantly lower than that in Bangladesh. Previously, we showed that primary human basal respiratory epithelial cells are susceptible to both NiV-Malaysia (M) and -Bangladesh (B) strains causing robust pro-inflammatory responses. However, the cells of the human respiratory epithelium that NiV targets are unknown and their role in NiV transmission and NiV-related lung pathogenesis is still poorly understood. Here, we characterized NiV infection of the human respiratory epithelium using a model of the human tracheal/bronchial (B-ALI) and small airway (S-ALI) epithelium cultured at an air-liquid interface. We show that NiV-M and NiV-B infect ciliated and secretory cells in B/S-ALI, and that infection of S-ALI, but not B-ALI, results in disruption of the epithelium integrity and host responses recruiting human immune cells. Interestingly, NiV-B replicated more efficiently in B-ALI than did NiV-M. These results suggest that the human tracheal/bronchial epithelium is favourable to NiV replication and shedding, while inducing a limited host response. Our data suggest that the small airways epithelium is prone to inflammation and lesions as well as constituting a point of virus entry into the pulmonary vasculature. The use of relevant models of the human respiratory tract, such as B/S-ALI, is critical for understanding NiV-related lung pathogenesis and identifying the underlying mechanisms allowing human-to-human transmission.

Human Adenovirus Associated with Severe Respiratory Infection, Oregon, USA, 2013–2014

PubMed Central

Chommanard, Christina; Lu, Xiaoyan; Appelgate, Dianna; Grenz, LaDonna; Schneider, Eileen; Gerber, Susan I.; Erdman, Dean D.; Thomas, Ann

2016-01-01

Several human adenoviruses (HAdVs) can cause respiratory infections, some severe. HAdV-B7, which can cause severe respiratory disease, has not been recently reported in the United States but is reemerging in Asia. During October 2013–July 2014, Oregon health authorities identified 198 persons with respiratory symptoms and an HAdV-positive respiratory tract specimen. Among 136 (69%) hospitalized persons, 31% were admitted to the intensive care unit and 18% required mechanical ventilation; 5 patients died. Molecular typing of 109 specimens showed that most (59%) were HAdV-B7, followed by HAdVs-C1, -C2, -C5 (26%); HAdVs-B3, -B21 (15%); and HAdV-E4 (1%). Molecular analysis of 7 HAdV-B7 isolates identified the virus as genome type d, a strain previously identified only among strains circulating in Asia. Patients with HAdV-B7 were significantly more likely than those without HAdV-B7 to be adults and to have longer hospital stays. HAdV-B7 might be reemerging in the United States, and clinicians should consider HAdV in persons with severe respiratory infection. PMID:27191834

A Review on the Respiratory System Toxicity of Carbon Nanoparticles.

PubMed

Pacurari, Maricica; Lowe, Kristine; Tchounwou, Paul B; Kafoury, Ramzi

2016-03-15

The respiratory system represents the main gateway for nanoparticles' entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles' interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products.

A Review on the Respiratory System Toxicity of Carbon Nanoparticles

PubMed Central

Pacurari, Maricica; Lowe, Kristine; Tchounwou, Paul B.; Kafoury, Ramzi

2016-01-01

The respiratory system represents the main gateway for nanoparticles’ entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles’ interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products. PMID:26999172

The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

PubMed

Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

2014-12-01

The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease

PubMed Central

Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J.; Tyler, Scott R.; Tisoncik-Go, Jennifer; Brawand, David; Law, G. Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J.; Kelly, Sara M.; Chang, Jean; Thomas, Matthew J.; Johnson, Jeremy; Berlin, Aaron M.; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M.; Tumpey, Terrence M.; Siepel, Adam; Wisely, Samantha M.; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W.; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F.; Palermo, Robert E.; Katze, Michael G.

2014-01-01

The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the ‘gold standard’ for modeling human influenza virus infection and transmission1–4. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotate 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterize the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time courses, and show distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis (CF) disease progression, we show that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with CF disease. PMID:25402615

A model of mechanical interactions between heart and lungs.

PubMed

Fontecave Jallon, Julie; Abdulhay, Enas; Calabrese, Pascale; Baconnier, Pierre; Gumery, Pierre-Yves

2009-12-13

To study the mechanical interactions between heart, lungs and thorax, we propose a mathematical model combining a ventilatory neuromuscular model and a model of the cardiovascular system, as described by Smith et al. (Smith, Chase, Nokes, Shaw & Wake 2004 Med. Eng. Phys.26, 131-139. (doi:10.1016/j.medengphy.2003.10.001)). The respiratory model has been adapted from Thibault et al. (Thibault, Heyer, Benchetrit & Baconnier 2002 Acta Biotheor. 50, 269-279. (doi:10.1023/A:1022616701863)); using a Liénard oscillator, it allows the activity of the respiratory centres, the respiratory muscles and rib cage internal mechanics to be simulated. The minimal haemodynamic system model of Smith includes the heart, as well as the pulmonary and systemic circulation systems. These two modules interact mechanically by means of the pleural pressure, calculated in the mechanical respiratory system, and the intrathoracic blood volume, calculated in the cardiovascular model. The simulation by the proposed model provides results, first, close to experimental data, second, in agreement with the literature results and, finally, highlighting the presence of mechanical cardiorespiratory interactions.

Acute effects on cardiovascular oscillations during controlled slow yogic breathing.

PubMed

Bhagat, Om Lata; Kharya, Chhaya; Jaryal, Ashok; Deepak, Kishore Kumar

2017-04-01

Breathing exercises are believed to modulate the cardiovascular oscillations in the body. To assess the validity of the assumption and understand the underlying mechanism, the key autonomic regulatory parameters such as heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were recorded during controlled slow yogic breathing. Alternate nostril breathing (ANB) was selected as the yogic manoeuvre. Twelve healthy volunteers (age 30±3.8 yr) participated in the study. ANB was performed at a breathing frequency of 5 breaths per minute (bpm). In each participant, the electrocardiogram, respiratory movements, beat-to-beat BP and end-tidal carbon dioxide were recorded for five minutes each: before, during and after ANB. The records were analyzed for HRV, BPV and BRS. During ANB, HRV analysis showed significant increase in the standard deviation of all NN intervals, low-frequency (LF) component, LF/HF (low frequency/high frequency) ratio and significant decrease in the HF component. BPV analysis showed a significant increase in total power in systolic BPV (SBPV), diastolic BPV (DBPV) and mean BPV. BRS analysis showed a significant increase in the total number of sequences in SBPV and DBPV and significant augmentation of α-LF and reduction in α-HF. The power spectrum showed a dominant peak in HRV at 0.08 Hz (LF component) similar to the respiratory frequency. The acute short-term change in circulatory control system declined immediately after the cessation of slow yogic breathing (ANB) and remained elevated in post-ANB stage as compared to the pre-ANB. Significant increase in cardiovascular oscillations and baroreflex recruitments during-ANB suggested a dynamic interaction between respiratory and cardiovascular system. Enhanced phasic relationship with some delay indicated the complexity of the system. It indicated that respiratory and cardiovascular oscillations were coupled through multiple regulatory mechanisms, such as

Impaired central respiratory chemoreflex in an experimental genetic model of epilepsy

PubMed Central

Totola, Leonardo T.; Takakura, Ana C.; Oliveira, José Antonio C.

2016-01-01

Key points It is recognized that seizures commonly cause apnoea and oxygen desaturation, but there is still a lack in the literature about the respiratory impairments observed ictally and in the post‐ictal period.Respiratory disorders may involve changes in serotonergic transmission at the level of the retrotrapezoid nucleus (RTN).In this study, we evaluated breathing activity and the role of serotonergic transmission in the RTN with a rat model of tonic–clonic seizures, the Wistar audiogenic rat (WAR).We conclude that the respiratory impairment in the WAR could be correlated to an overall decrease in the number of neurons located in the respiratory column. Abstract Respiratory disorders may involve changes in serotonergic neurotransmission at the level of the chemosensitive neurons located in the retrotrapezoid nucleus (RTN). Here, we investigated the central respiratory chemoreflex and the role of serotonergic neurotransmission in the RTN with a rat model of tonic–clonic seizures, the Wistar audiogenic rat (WAR). We found that naive or kindled WARs have reduced resting ventilation and ventilatory response to hypercapnia (7% CO2). The number of chemically coded (Phox2b+/TH−) RTN neurons, as well as the serotonergic innervation to the RTN, was reduced in WARs. We detected that the ventilatory response to serotonin (1 mm, 50 nl) within the RTN region was significantly reduced in WARs. Our results uniquely demonstrated a respiratory impairment in a genetic model of tonic–clonic seizures, the WAR strain. More importantly, we demonstrated an overall decrease in the number of neurons located in the ventral respiratory column (VRC), as well as a reduction in serotonergic neurons in the midline medulla. This is an important step forward to demonstrate marked changes in neuronal activity and breathing impairment in the WAR strain, a genetic model of epilepsy. PMID:27633663

Effects of Human Metapneumovirus and Respiratory Syncytial Virus Antigen Insertion in Two 3′ Proximal Genome Positions of Bovine/Human Parainfluenza Virus Type 3 on Virus Replication and Immunogenicity

PubMed Central

Tang, Roderick S.; Schickli, Jeanne H.; MacPhail, Mia; Fernandes, Fiona; Bicha, Leenas; Spaete, Joshua; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.; Spaete, Richard; Haller, Aurelia A.

2003-01-01

A live attenuated bovine parainfluenza virus type 3 (PIV3), harboring the fusion (F) and hemagglutinin-neuraminidase (HN) genes of human PIV3, was used as a virus vector to express surface glycoproteins derived from two human pathogens, human metapneumovirus (hMPV) and respiratory syncytial virus (RSV). RSV and hMPV are both paramyxoviruses that cause respiratory disease in young children, the elderly, and immunocompromised individuals. RSV has been known for decades to cause acute lower respiratory tract infections in young children, which often result in hospitalization, while hMPV has only been recently identified as a novel human respiratory pathogen. In this study, the ability of bovine/human PIV3 to express three different foreign transmembrane surface glycoproteins and to induce a protective immune response was evaluated. The RNA-dependent RNA polymerase of paramyxoviruses binds to a single site at the 3′ end of the viral RNA genome to initiate transcription of viral genes. The genome position of the viral gene determines its level of gene expression. The promoter-proximal gene is transcribed with the highest frequency, and each downstream gene is transcribed less often due to attenuation of transcription at each gene junction. This feature of paramyxoviruses was exploited using the PIV3 vector by inserting the foreign viral genes at the 3′ terminus, at position 1 or 2, of the viral RNA genome. These locations were expected to yield high levels of foreign viral protein expression stimulating a protective immune response. The immunogenicity and protection results obtained with a hamster model showed that bovine/human PIV3 can be employed to generate bivalent PIV3/RSV or PIV3/hMPV vaccine candidates that will be further evaluated for safety and efficacy in primates. PMID:14512532

Estrogen receptor β actions in the female cardiovascular system: A systematic review of animal and human studies.

PubMed

Muka, Taulant; Vargas, Kris G; Jaspers, Loes; Wen, Ke-xin; Dhana, Klodian; Vitezova, Anna; Nano, Jana; Brahimaj, Adela; Colpani, Veronica; Bano, Arjola; Kraja, Bledar; Zaciragic, Asija; Bramer, Wichor M; van Dijk, Gaby M; Kavousi, Maryam; Franco, Oscar H

2016-04-01

Five medical databases were searched for studies that assessed the role of ERβ in the female cardiovascular system and the influence of age and menopause on ERβ functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERβ signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERβ signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERβ may be vessel specific and may differ by age and menopause status. ERβ seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERβ-ligands might contribute to cardiovascular disease prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reintrepreting the cardiovascular system as a mechanical model

NASA Astrophysics Data System (ADS)

Lemos, Diogo; Machado, José; Minas, Graça; Soares, Filomena; Barros, Carla; Leão, Celina Pinto

2013-10-01

The simulation of the different physiological systems is very useful as a pedagogical tool, allowing a better understanding of the mechanisms and the functions of the processes. The observation of the physiological phenomena through mechanical simulators represents a great asset. Furthermore, the development of these simulators allows reinterpreting physiological systems, with the advantage of using the same transducers and sensors that are commonly used in diagnostic and therapeutic cardiovascular procedures for the monitoring of system' parameters. The cardiovascular system is one of the most important systems of the human body and has been the target of several biomedical studies. The present work describes a mechanical simulation of the cardiovascular system, in particularly, the systemic circulation, which can be described in terms of its hemodynamic variables. From the mechanical process and parameters, physiological system's behavior was reproduced, as accurately as possible.

A Multiscale Closed-Loop Cardiovascular Model, with Applications to Heart Pacing and Hemorrhage

NASA Astrophysics Data System (ADS)

Canuto, Daniel; Eldredge, Jeff; Chong, Kwitae; Benharash, Peyman; Dutson, Erik

2017-11-01

A computational tool is developed for simulating the dynamic response of the human cardiovascular system to various stressors and injuries. The tool couples zero-dimensional models of the heart, pulmonary vasculature, and peripheral vasculature to one-dimensional models of the major systemic arteries. To simulate autonomic response, this multiscale circulatory model is integrated with a feedback model of the baroreflex, allowing control of heart rate, cardiac contractility, and peripheral impedance. The performance of the tool is demonstrated in two scenarios: increasing heart rate by stimulating the sympathetic nervous system, and an acute 10 percent hemorrhage from the left femoral artery.

Integrative approaches for modeling regulation and function of the respiratory system.

PubMed

Ben-Tal, Alona; Tawhai, Merryn H

2013-01-01

Mathematical models have been central to understanding the interaction between neural control and breathing. Models of the entire respiratory system-which comprises the lungs and the neural circuitry that controls their ventilation-have been derived using simplifying assumptions to compartmentalize each component of the system and to define the interactions between components. These full system models often rely-through necessity-on empirically derived relationships or parameters, in addition to physiological values. In parallel with the development of whole respiratory system models are mathematical models that focus on furthering a detailed understanding of the neural control network, or of the several functions that contribute to gas exchange within the lung. These models are biophysically based, and rely on physiological parameters. They include single-unit models for a breathing lung or neural circuit, through to spatially distributed models of ventilation and perfusion, or multicircuit models for neural control. The challenge is to bring together these more recent advances in models of neural control with models of lung function, into a full simulation for the respiratory system that builds upon the more detailed models but remains computationally tractable. This requires first understanding the mathematical models that have been developed for the respiratory system at different levels, and which could be used to study how physiological levels of O2 and CO2 in the blood are maintained. Copyright © 2013 Wiley Periodicals, Inc.

Cardiovascular physiology and diseases of the rabbit.

PubMed

Pariaut, Romain

2009-01-01

This article reviews what is known about the diagnosis and management of cardiovascular diseases in the pet rabbit. Current knowledge is based on anecdotal reports, derived from research data using the rabbit as an animal model of human cardiovascular diseases, but most importantly canine and feline cardiology. It is likely that, as cardiovascular diseases are more often recognized, more specific information will soon become available for the treatment of the pet rabbit with cardiac disease.

Cardiovascular adaptations supporting human exercise-heat acclimation.

PubMed

Périard, Julien D; Travers, Gavin J S; Racinais, Sébastien; Sawka, Michael N

2016-04-01

This review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heat acclimation. The cardiovascular system is well recognized as an important contributor to exercise-heat acclimation that acts to minimize physiological strain, reduce the risk of serious heat illness and better sustain exercise capacity. The upright posture adopted by humans during most physical activities and the large skin surface area contribute to the circulatory and blood pressure regulation challenge of simultaneously supporting skeletal muscle blood flow and dissipating heat via increased skin blood flow and sweat secretion during exercise-heat stress. Although it was traditionally held that cardiac output increased during exercise-heat stress to primarily support elevated skin blood flow requirements, recent evidence suggests that temperature-sensitive mechanisms may also mediate an elevation in skeletal muscle blood flow. The cardiovascular adaptations supporting this challenge include an increase in total body water, plasma volume expansion, better sustainment and/or elevation of stroke volume, reduction in heart rate, improvement in ventricular filling and myocardial efficiency, and enhanced skin blood flow and sweating responses. The magnitude of these adaptations is variable and dependent on several factors such as exercise intensity, duration of exposure, frequency and total number of exposures, as well as the environmental conditions (i.e. dry or humid heat) in which acclimation occurs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia

PubMed Central

Alshrari, Ahmed S.; Badroon, Nassrin A.; Hassan, Ahmed M.; Alsubhi, Tagreed L.; Ejeeli, Saleh

2017-01-01

We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control. PMID:28348590

Insights into the transmission of respiratory infectious diseases through empirical human contact networks

PubMed Central

Huang, Chunlin; Liu, Xingwu; Sun, Shiwei; Li, Shuai Cheng; Deng, Minghua; He, Guangxue; Zhang, Haicang; Wang, Chao; Zhou, Yang; Zhao, Yanlin; Bu, Dongbo

2016-01-01

In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology. Furthermore, the special contact pattern within Chinese colleges results in disease spreading patterns distinct from those of the US schools. Remarkably, class cancelation, though simple, shows a mitigating power equal to quarantine/vaccination applied on ~25% of college students, which quantitatively explains its success in Chinese colleges during the SARS period. Our findings greatly facilitate reliable prediction of epidemic prevalence, and thus should help establishing effective strategies for respiratory infectious diseases control. PMID:27526868

Ambient air pollution exposure and respiratory, cardiovascular and cerebrovascular mortality in Cape Town, South Africa: 2001–2006.

PubMed

Wichmann, Janine; Voyi, Kuku

2012-11-05

Little evidence is available on the strength of the association between ambient air pollution exposure and health effects in developing countries such as South Africa. The association between the 24-h average ambient PM(10), SO(2) and NO(2) levels and daily respiratory (RD), cardiovascular (CVD) and cerebrovascular (CBD) mortality in Cape Town (2001-2006) was investigated with a case-crossover design. For models that included entire year data, an inter-quartile range (IQR) increase in PM(10) (12 mg/m3) and NO(2) (12 mg/m3) significantly increased CBD mortality by 4% and 8%, respectively. A significant increase of 3% in CVD mortality was observed per IQR increase in NO(2) and SO(2) (8 mg/m3). In the warm period, PM(10) was significantly associated with RD and CVD mortality. NO(2) had significant associations with CBD, RD and CVD mortality, whilst SO(2) was associated with CVD mortality. None of the pollutants were associated with any of the three outcomes in the cold period. Susceptible groups depended on the cause-specific mortality and air pollutant. There is significant RD, CVD and CBD mortality risk associated with ambient air pollution exposure in South Africa, higher than reported in developed countries.

The human cardiovascular system during space flight

NASA Astrophysics Data System (ADS)

Grigoriev, A. I.; Kotovskaya, A. R.; Fomina, G. A.

2011-05-01

Purpose of the work is to analyze and to summarize the data of investigations into human hemodynamics performed over 20 years aboard orbital stations Salyut-7 and Mir with participation of 26 cosmonauts on space flights (SF) from 8 to 438 days in duration. The ultrasonic techniques and occlusive plethysmography demonstrated dynamics of changes in the cardiovascular system during SF of various durations. The parameters of general hemodynamics, the pumping function of the heart and arterial circulation in the brain remained stable in all the space flights; however, there were alterations in peripheral circulation associated with blood redistribution and hypovolemie in microgravity. The anti-gravity distribution of the vascular tone decayed gradually as unneeded. The most considerable changes were observed in leg vessels, equally in arteries (decrease in resistance) and veins (increase in maximum capacity). The lower body negative pressure test (LBNP) revealed deterioration of the gravity-dependent reactions that changed for the worse as SF duration extended. The cardiovascular deconditioning showed itself as loss of descent acceleration tolerance and orthostatic instability in the postflight period.

Component-specific, cigarette particle deposition modeling in the human respiratory tract

PubMed Central

Price, Owen T.; Yurteri, Caner U.; Dickens, Colin; McAughey, John

2014-01-01

Inhalation of cigarette smoke particles (CSP) leads to adverse health effects in smokers. Determination of the localized dose to the lung of the inhaled smoke aids in determining vulnerable sites, and identifying components of the smoke that may be responsible for the adverse effects; thus providing a roadmap for harm reduction of cigarette smoking. A particle deposition model specific to CSP was developed for the oral cavity and the lung by accounting for cigarette particle size growth by hygroscopicity, phase change and coagulation. In addition, since the cigarette puff enters the respiratory tract as a dense cloud, the cloud effect on particle drag and deposition was accounted for in the deposition model. Models of particle losses in the oral cavities were developed during puff drawing and subsequent mouth-hold. Cigarette particles were found to grow by hygroscopicity and coagulation, but to shrink as a result of nicotine evaporation. The particle size reached a plateau beyond which any disturbances in the environmental conditions caused the various mechanisms to balance each other out and the particle size remain stable. Predicted particle deposition considering the cloud effects was greater than when treated as a collection of non-interacting particles (i.e. no cloud effects). Accounting for cloud movement provided the necessary physical mechanism to explain the greater than expected, experimentally observed and particle deposition. The deposition model for CSP can provide the necessary input to determine the fate of inhaled CSP in the lung. The knowledge of deposition will be helpful for health assessment and identification and reduction of harmful components of CSP. PMID:24354791

Stress, depression, and cardiovascular dysregulation: A review of neurobiological mechanisms and the integration of research from preclinical disease models

PubMed Central

Grippo, Angela J.; Johnson, Alan Kim

2008-01-01

A bidirectional association between mood disorders such as depression, and cardiovascular diseases such as myocardial infarction and congestive heart failure, has been described; however, the precise neurobiological mechanisms that underlie these associations have not been fully elucidated. This review is focused on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders, with an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction including dopamine, norepinephrine and serotonin, and (e) behavioral changes including fatigue and physical inactivity. We also focus specifically on experimental investigations with preclinical disease models, conducted to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with the extensive literature describing findings from human research, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and can promote the development of better treatments and interventions for individuals with these co

Computational Motion Phantoms and Statistical Models of Respiratory Motion

NASA Astrophysics Data System (ADS)

Ehrhardt, Jan; Klinder, Tobias; Lorenz, Cristian

Breathing motion is not a robust and 100 % reproducible process, and inter- and intra-fractional motion variations form an important problem in radiotherapy of the thorax and upper abdomen. A widespread consensus nowadays exists that it would be useful to use prior knowledge about respiratory organ motion and its variability to improve radiotherapy planning and treatment delivery. This chapter discusses two different approaches to model the variability of respiratory motion. In the first part, we review computational motion phantoms, i.e. computerized anatomical and physiological models. Computational phantoms are excellent tools to simulate and investigate the effects of organ motion in radiation therapy and to gain insight into methods for motion management. The second part of this chapter discusses statistical modeling techniques to describe the breathing motion and its variability in a population of 4D images. Population-based models can be generated from repeatedly acquired 4D images of the same patient (intra-patient models) and from 4D images of different patients (inter-patient models). The generation of those models is explained and possible applications of those models for motion prediction in radiotherapy are exemplified. Computational models of respiratory motion and motion variability have numerous applications in radiation therapy, e.g. to understand motion effects in simulation studies, to develop and evaluate treatment strategies or to introduce prior knowledge into the patient-specific treatment planning.

Long-term regulation in the cardiovascular system - Cornerstone in the development of a composite physiological model

NASA Technical Reports Server (NTRS)

White, R. J.

1974-01-01

The present work discusses a model of the cardiovascular system and related subsystems capable of long-term simulations of the type desired for in-space hypogravic human physiological performance prediction. The discussion centers around the model of Guyton and modifications of it. In order to draw attention to the fluid handling capabilities of the model, one of several transfusion simulations performed is presented, namely, the isotonic saline transfusion simulation.

Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses.

PubMed

Chan, Renee W Y; Chan, Michael C W; Nicholls, John M; Malik Peiris, J S

2013-12-05

The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo. The state of differentiation of primary human cells (respiratory epithelium, macrophages) can markedly affect virus tropism and host responses. Ex vivo cultures of human respiratory tissues provide a close resemblance to tissues in vivo and may be used to risk assess animal viruses for pandemic threat. Physiological factors (age, inflammation) can markedly affect virus receptor expression and virus tropism. Taken together with data from clinical studies on infected humans and relevant animal models, data from ex vivo and in vitro cultures of human tissues and cells can provide insights into virus transmission and pathogenesis and may provide understanding that leads to novel therapeutic interventions. Copyright © 2013 Elsevier B.V. All rights reserved.

Computational Models of the Cardiovascular System and Its Response to Microgravity

NASA Technical Reports Server (NTRS)

Kamm, Roger D.

1999-01-01

Computational models of the cardiovascular system are powerful adjuncts to ground-based and in-flight experiments. We will provide NSBRI with a model capable of simulating the short-term effects of gravity on cardiovascular function. The model from this project will: (1) provide a rational framework which quantitatively defines interactions among complex cardiovascular parameters and which supports the critical interpretation of experimental results and testing of hypotheses. (2) permit predictions of the impact of specific countermeasures in the context of various hypothetical cardiovascular abnormalities induced by microgravity. Major progress has been made during the first 18 months of the program: (1) We have developed an operational first-order computer model capable of simulating the cardiovascular response to orthostatic stress. The model consists of a lumped parameter hemodynamic model and a complete reflex control system. The latter includes cardiopulmonary and carotid sinus reflex limbs and interactions between the two. (2) We have modeled the physiologic stress of tilt table experiments and lower body negative pressure procedures (LBNP). We have verified our model's predictions by comparing them with experimental findings from the literature. (3) We have established collaborative efforts with leading investigators interested in experimental studies of orthostatic intolerance, cardiovascular control, and physiologic responses to space flight. (4) We have established a standardized method of transferring data to our laboratory from the ongoing NSBRI bedrest studies. We use this data to estimate input parameters to our model and compare our model predictions to actual data to further verify our model. (5) We are in the process of systematically simulating current hypotheses concerning the mechanism underlying orthostatic intolerance by matching our simulations to stand test data from astronauts pre- and post-flight. (6) We are in the process of developing a

Vestibular influences on autonomic cardiovascular control in humans

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Costa, F.; Kaufmann, H.; Robertson, D. (Principal Investigator)

1998-01-01

There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baroreflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

PubMed Central

Satterfield, Benjamin A.; Cross, Robert W.; Fenton, Karla A.; Borisevich, Viktoriya; Agans, Krystle N.; Deer, Daniel J.; Graber, Jessica; Basler, Christopher F.; Mire, Chad E.

2016-01-01

ABSTRACT Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. IMPORTANCE Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced

General Pharmacology of Artesunate, a Commonly used Antimalarial Drug:Effects on Central Nervous, Cardiovascular, and Respiratory System

PubMed Central

Lee, Hyang-Ae; Kim, Ki-Suk

2010-01-01

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR) , and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial) . Thus, it can be concluded that artesunate is safe at clinical therapeutic doses. PMID:24278528

Simulation of a G-tolerance curve using the pulsatile cardiovascular model

NASA Technical Reports Server (NTRS)

Solomon, M.; Srinivasan, R.

1985-01-01

A computer simulation study, performed to assess the ability of the cardiovascular model to reproduce the G tolerance curve (G level versus tolerance time) is reported. A composite strength duration curve derived from experimental data obtained in human centrifugation studies was used for comparison. The effects of abolishing automomic control and of blood volume loss on G tolerance were also simulated. The results provide additional validation of the model. The need for the presence of autonomic reflexes even at low levels of G is pointed out. The low margin of safety with a loss of blood volume indicated by the simulation results underscores the necessity for protective measures during Shuttle reentry.

Human coronavirus and severe acute respiratory infection in Southern Brazil.

PubMed

Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

2016-05-01

Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p < 0.001), and HCoV accounted for 6% of the SARI cases. Three patients infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

Human bocavirus in children with acute respiratory infections in Vietnam.

PubMed

Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

2014-06-01

Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value <0.05). Co-infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model

PubMed Central

Wang, Zhaoxuan; Talaat, Khaled; Glide-Hurst, Carri; Dong, Haibo

2018-01-01

Background Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in silico studies. The objective of this study is to develop a computational acoustic model of human airways with a dynamic glottis and quantify the effects of glottis motion and tidal breathing on airflow and sound generation. Methods Large eddy simulation and FW-H models were adopted to compute airflows and respiratory sounds in an image-based mouth-lung model. User-defined functions were developed that governed the glottis kinematics. Varying breathing scenarios (static vs. dynamic glottis; constant vs. sinusoidal inhalations) were simulated to understand the effects of glottis motion and inhalation pattern on sound generation. Pressure distributions were measured in airway casts with different glottal openings for model validation purpose. Results Significant flow fluctuations were predicted in the upper airways at peak inhalation rates or during glottal constriction. The inhalation speed through the glottis was the predominating factor in the sound generation while the transient effects were less important. For all frequencies considered (20–2500 Hz), the static glottis substantially underestimated the intensity of the generated sounds, which was most pronounced in the range of 100–500 Hz. Adopting an equivalent steady flow rather than a tidal breathing further underestimated the sound intensity. An increase of 25 dB in average was observed for the life condition (sine-dynamic) compared to the idealized condition (constant-rigid) for the broadband frequencies, with the largest increase of approximately 40 dB at the frequency around 250 Hz. Conclusion Results show that a severely narrowing glottis during inhalation, as

Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model.

PubMed

Xi, Jinxiang; Wang, Zhaoxuan; Talaat, Khaled; Glide-Hurst, Carri; Dong, Haibo

2018-05-01

Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in silico studies. The objective of this study is to develop a computational acoustic model of human airways with a dynamic glottis and quantify the effects of glottis motion and tidal breathing on airflow and sound generation. Large eddy simulation and FW-H models were adopted to compute airflows and respiratory sounds in an image-based mouth-lung model. User-defined functions were developed that governed the glottis kinematics. Varying breathing scenarios (static vs. dynamic glottis; constant vs. sinusoidal inhalations) were simulated to understand the effects of glottis motion and inhalation pattern on sound generation. Pressure distributions were measured in airway casts with different glottal openings for model validation purpose. Significant flow fluctuations were predicted in the upper airways at peak inhalation rates or during glottal constriction. The inhalation speed through the glottis was the predominating factor in the sound generation while the transient effects were less important. For all frequencies considered (20-2500 Hz), the static glottis substantially underestimated the intensity of the generated sounds, which was most pronounced in the range of 100-500 Hz. Adopting an equivalent steady flow rather than a tidal breathing further underestimated the sound intensity. An increase of 25 dB in average was observed for the life condition (sine-dynamic) compared to the idealized condition (constant-rigid) for the broadband frequencies, with the largest increase of approximately 40 dB at the frequency around 250 Hz. Results show that a severely narrowing glottis during inhalation, as well as flow fluctuations in the

Transient cardio-respiratory responses to visually induced tilt illusions

NASA Technical Reports Server (NTRS)

Wood, S. J.; Ramsdell, C. D.; Mullen, T. J.; Oman, C. M.; Harm, D. L.; Paloski, W. H.

2000-01-01

Although the orthostatic cardio-respiratory response is primarily mediated by the baroreflex, studies have shown that vestibular cues also contribute in both humans and animals. We have demonstrated a visually mediated response to illusory tilt in some human subjects. Blood pressure, heart and respiration rate, and lung volume were monitored in 16 supine human subjects during two types of visual stimulation, and compared with responses to real passive whole body tilt from supine to head 80 degrees upright. Visual tilt stimuli consisted of either a static scene from an overhead mirror or constant velocity scene motion along different body axes generated by an ultra-wide dome projection system. Visual vertical cues were initially aligned with the longitudinal body axis. Subjective tilt and self-motion were reported verbally. Although significant changes in cardio-respiratory parameters to illusory tilts could not be demonstrated for the entire group, several subjects showed significant transient decreases in mean blood pressure resembling their initial response to passive head-up tilt. Changes in pulse pressure and a slight elevation in heart rate were noted. These transient responses are consistent with the hypothesis that visual-vestibular input contributes to the initial cardiovascular adjustment to a change in posture in humans. On average the static scene elicited perceived tilt without rotation. Dome scene pitch and yaw elicited perceived tilt and rotation, and dome roll motion elicited perceived rotation without tilt. A significant correlation between the magnitude of physiological and subjective reports could not be demonstrated.

A forward model-based validation of cardiovascular system identification

NASA Technical Reports Server (NTRS)

Mukkamala, R.; Cohen, R. J.

2001-01-01

We present a theoretical evaluation of a cardiovascular system identification method that we previously developed for the analysis of beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure, and instantaneous lung volume. The method provides a dynamical characterization of the important autonomic and mechanical mechanisms responsible for coupling the fluctuations (inverse modeling). To carry out the evaluation, we developed a computational model of the cardiovascular system capable of generating realistic beat-to-beat variability (forward modeling). We applied the method to data generated from the forward model and compared the resulting estimated dynamics with the actual dynamics of the forward model, which were either precisely known or easily determined. We found that the estimated dynamics corresponded to the actual dynamics and that this correspondence was robust to forward model uncertainty. We also demonstrated the sensitivity of the method in detecting small changes in parameters characterizing autonomic function in the forward model. These results provide confidence in the performance of the cardiovascular system identification method when applied to experimental data.

Practical identifiability analysis of a minimal cardiovascular system model.

PubMed

Pironet, Antoine; Docherty, Paul D; Dauby, Pierre C; Chase, J Geoffrey; Desaive, Thomas

2017-01-17

Parameters of mathematical models of the cardiovascular system can be used to monitor cardiovascular state, such as total stressed blood volume status, vessel elastance and resistance. To do so, the model parameters have to be estimated from data collected at the patient's bedside. This work considers a seven-parameter model of the cardiovascular system and investigates whether these parameters can be uniquely determined using indices derived from measurements of arterial and venous pressures, and stroke volume. An error vector defined the residuals between the simulated and reference values of the seven clinically available haemodynamic indices. The sensitivity of this error vector to each model parameter was analysed, as well as the collinearity between parameters. To assess practical identifiability of the model parameters, profile-likelihood curves were constructed for each parameter. Four of the seven model parameters were found to be practically identifiable from the selected data. The remaining three parameters were practically non-identifiable. Among these non-identifiable parameters, one could be decreased as much as possible. The other two non-identifiable parameters were inversely correlated, which prevented their precise estimation. This work presented the practical identifiability analysis of a seven-parameter cardiovascular system model, from limited clinical data. The analysis showed that three of the seven parameters were practically non-identifiable, thus limiting the use of the model as a monitoring tool. Slight changes in the time-varying function modeling cardiac contraction and use of larger values for the reference range of venous pressure made the model fully practically identifiable. Copyright © 2017. Published by Elsevier B.V.

Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?

PubMed Central

Siemens, Nikolai; Oehmcke-Hecht, Sonja; Mettenleiter, Thomas C.; Kreikemeyer, Bernd; Valentin-Weigand, Peter; Hammerschmidt, Sven

2017-01-01

Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract. Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia. In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease. Transmission of IAV and pneumonia is mainly modeled by mouse infection. Few studies utilizing ferrets, rats, guinea pigs, rabbits, and non-human primates are also available. The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases. Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans. Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health. PMID:29312268

The lung mycobiome: an emerging field of the human respiratory microbiome

PubMed Central

Nguyen, Linh D. N.; Viscogliosi, Eric; Delhaes, Laurence

2015-01-01

The lung microbiome, which is believed to be stable or at least transient in healthy people, is now considered as a poly-microorganism component contributing to disease pathogenesis. Most research studies on the respiratory microbiome have focused on bacteria and their impact on lung health, but there is evidence that other non-bacterial organisms, comprising the viruses (virome) and fungi (mycobiome), are also likely to play an important role in healthy people as well as in patients. In the last few years, the lung mycobiome (previously named the fungal microbiota or microbiome) has drawn closer attention. There is growing evidence that the lung mycobiome has a significant impact on clinical outcome of chronic respiratory diseases (CRD) such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and bronchiectasis. Thanks to advances in culture independent methods, especially next generation sequencing, a number of fungi not detected by culture methods have been molecularly identified in human lungs. It has been shown that the structure and diversity of the lung mycobiome vary in different populations (healthy and different diseased individuals) which could play a role in CRD. Moreover, the link between lung mycobiome and different biomes of other body sites, especially the gut, has also been unraveled. By interacting with the bacteriome and/or virome, the respiratory mycobiome appears to be a cofactor in inflammation and in the host immune response, and therefore may contribute to the decline of the lung function and the disease progression. In this review, we report the recent limited explorations of the human respiratory mycobiome, and discuss the mycobiome’s connections with other local microbial communities, as well as the relationships with the different biomes of other body sites. These studies suggest several outlooks for this understudied emerging field, which will certainly call for a renewal of our understanding of pulmonary diseases. PMID

Modelling in vivo creatine/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise.

PubMed

Ydfors, Mia; Hughes, Meghan C; Laham, Robert; Schlattner, Uwe; Norrbom, Jessica; Perry, Christopher G R

2016-06-01

Mitochondrial respiratory sensitivity to ADP is thought to influence muscle fitness and is partly regulated by cytosolic-mitochondrial diffusion of ADP or phosphate shuttling via creatine/phosphocreatine (Cr/PCr) through mitochondrial creatine kinase (mtCK). Previous measurements of respiration in vitro with Cr (saturate mtCK) or without (ADP/ATP diffusion) show mixed responses of ADP sensitivity following acute exercise vs. less sensitivity after chronic exercise. In human muscle, modelling in vivo 'exercising' [Cr:PCr] during in vitro assessments revealed novel responses to exercise that differ from detections with or without Cr (±Cr). Acute exercise increased ADP sensitivity when measured without Cr but had no effect ±Cr or with +Cr:PCr, whereas chronic exercise increased sensitivity ±Cr but lowered sensitivity with +Cr:PCr despite increased markers of mitochondrial oxidative capacity. Controlling in vivo conditions during in vitro respiratory assessments reveals responses to exercise that differ from typical ±Cr comparisons and challenges our understanding of how exercise improves metabolic control in human muscle. Mitochondrial respiratory control by ADP (Kmapp ) is viewed as a critical regulator of muscle energy homeostasis. However, acute exercise increases, decreases or has no effect on Kmapp in human muscle, whereas chronic exercise surprisingly decreases sensitivity despite greater mitochondrial content. We hypothesized that modelling in vivo mitochondrial creatine kinase (mtCK)-dependent phosphate-shuttling conditions in vitro would reveal increased sensitivity (lower Kmapp ) after acute and chronic exercise. The Kmapp was determined in vitro with 20 mm Cr (+Cr), 0 mm Cr (-Cr) or 'in vivo exercising' 20 mm Cr/2.4 mm PCr (Cr:PCr) on vastus lateralis biopsies sampled from 11 men before, immediately after and 3 h after exercise on the first, fifth and ninth sessions over 3 weeks. Dynamic responses to acute exercise occurred throughout training

Lung injury and respiratory mechanics in rugby union.

PubMed

Lindsay, Angus; Bernard, Angelique; Davidson, Shaun M; Redmond, Daniel P; Chiew, Yeong S; Pretty, Christopher; Chase, J Geoffrey; Shaw, Geoffrey M; Gieseg, Steven P; Draper, Nick

2016-04-01

Rugby is a highly popular team contact sport associated with high injury rates. Specifically, there is a chance of inducing internal lung injuries as a result of the physical nature of the game. Such injuries are only identified with the use of specific invasive protocols or equipment. This study presents a model-based method to assess respiratory mechanics of N=11 rugby players that underwent a low intensity experimental Mechanical Ventilation (MV) Test before and after a rugby game. Participants were connected to a ventilator via a facemask and their respiratory mechanics estimated using a time-varying elastance model. All participants had a respiratory elastance <10 cmH2O/L with no significant difference observed between pre and postgame respiratory mechanics (P>0.05). Model-based respiratory mechanics estimation has been used widely in the treatment of the critically ill in intensive care. However, the application of a ventilator to assess the respiratory mechanics of healthy human beings is limited. This method adapted from ICU mechanical ventilation can be used to provide insight to respiratory mechanics of healthy participants that can be used as a more precise measure of lung inflammation/injury that avoids invasive procedures. This is the first study to conceptualize the assessment of respiratory mechanics in healthy athletes as a means to monitor postexercise stress and therefore manage recovery.

History of Music Therapy and Its Contemporary Applications in Cardiovascular Diseases.

PubMed

Montinari, Maria Rosa; Giardina, Simona; Minelli, Pierluca; Minelli, Sergio

2018-02-01

Contrary to what is commonly believed, music therapy is an old cure, the use of which is lost in the mists of time. Music always has been perceived to have particular healing powers, and the entire history of civilization contains aspects that link music to physical and mental healing. It seems that the adoption of music for therapeutic purposes harks back to a distant past, probably since the Paleolithic period: it was believed that listening to music could affect the behavior of human beings. In later centuries, the concept of "musical organ-tropism" was born and developed, because according to the type of music, one may affect the cardiovascular, respiratory, and neuroendocrine systems. Studies have shown that music can powerfully evoke and modulate emotions and moods, along with changes in heart activity, blood pressure, and breathing. Indeed, the following findings arise from the literature: heart and respiratory rates are higher in response to exciting music than in the case of tranquilizing music. In addition, music produces activity changes in brain structures (amygdala, hypothalamus, insular and orbitofrontal cortex) known to modulate heart function. This article provides a careful overview of music therapy history from prehistory to the present and a review of the latest applications of music therapy in cardiovascular diseases.

An Integrated Model of the Cardiovascular and Central Nervous Systems for Analysis of Microgravity Induced Fluid Redistribution

NASA Technical Reports Server (NTRS)

Price, R.; Gady, S.; Heinemann, K.; Nelson, E. S.; Mulugeta, L.; Ethier, C. R.; Samuels, B. C.; Feola, A.; Vera, J.; Myers, J. G.

2015-01-01

A recognized side effect of prolonged microgravity exposure is visual impairment and intracranial pressure (VIIP) syndrome. The medical understanding of this phenomenon is at present preliminary, although it is hypothesized that the headward shift of bodily fluids in microgravity may be a contributor. Computational models can be used to provide insight into the origins of VIIP. In order to further investigate this phenomenon, NASAs Digital Astronaut Project (DAP) is developing an integrated computational model of the human body which is divided into the eye, the cerebrovascular system, and the cardiovascular system. This presentation will focus on the development and testing of the computational model of an integrated model of the cardiovascular system (CVS) and central nervous system (CNS) that simulates the behavior of pressures, volumes, and flows within these two physiological systems.

Deposition of biomass combustion aerosol particles in the human respiratory tract.

PubMed

Löndahl, Jakob; Pagels, Joakim; Boman, Christoffer; Swietlicki, Erik; Massling, Andreas; Rissler, Jenny; Blomberg, Anders; Bohgard, Mats; Sandström, Thomas

2008-08-01

Smoke from biomass combustion has been identified as a major environmental risk factor associated with adverse health effects globally. Deposition of the smoke particles in the lungs is a crucial factor for toxicological effects, but has not previously been studied experimentally. We investigated the size-dependent respiratory-tract deposition of aerosol particles from wood combustion in humans. Two combustion conditions were studied in a wood pellet burner: efficient ("complete") combustion and low-temperature (incomplete) combustion simulating "wood smoke." The size-dependent deposition fraction of 15-to 680-nm particles was measured for 10 healthy subjects with a novel setup. Both aerosols were extensively characterized with regard to chemical and physical particle properties. The deposition was additionally estimated with the ICRP model, modified for the determined aerosol properties, in order to validate the experiments and allow a generalization of the results. The measured total deposited fraction of particles from both efficient combustion and low-temperature combustion was 0.21-0.24 by number, surface, and mass. The deposition behavior can be explained by the size distributions of the particles and by their ability to grow by water uptake in the lungs, where the relative humidity is close to saturation. The experiments were in basic agreement with the model calculations. Our findings illustrate: (1) that particles from biomass combustion obtain a size in the respiratory tract at which the deposition probability is close to its minimum, (2) that particle water absorption has substantial impact on deposition, and (3) that deposition is markedly influenced by individual factors.

Leveraging model-informed approaches for drug discovery and development in the cardiovascular space.

PubMed

Dockendorf, Marissa F; Vargo, Ryan C; Gheyas, Ferdous; Chain, Anne S Y; Chatterjee, Manash S; Wenning, Larissa A

2018-06-01

Cardiovascular disease remains a significant global health burden, and development of cardiovascular drugs in the current regulatory environment often demands large and expensive cardiovascular outcome trials. Thus, the use of quantitative pharmacometric approaches which can help enable early Go/No Go decision making, ensure appropriate dose selection, and increase the likelihood of successful clinical trials, have become increasingly important to help reduce the risk of failed cardiovascular outcomes studies. In addition, cardiovascular safety is an important consideration for many drug development programs, whether or not the drug is designed to treat cardiovascular disease; modeling and simulation approaches also have utility in assessing risk in this area. Herein, examples of modeling and simulation applied at various stages of drug development, spanning from the discovery stage through late-stage clinical development, for cardiovascular programs are presented. Examples of how modeling approaches have been utilized in early development programs across various therapeutic areas to help inform strategies to mitigate the risk of cardiovascular-related adverse events, such as QTc prolongation and changes in blood pressure, are also presented. These examples demonstrate how more informed drug development decisions can be enabled by modeling and simulation approaches in the cardiovascular area.

Involvement of the raphe in the respiratory effects of gigantocellular area activation.

PubMed

Richard, C A; Stremel, R W

1990-07-01

Previous reports indicate that the nucleus reticularis gigantocellularis (NGC) of the brainstem reticular formation is involved in inhibitory respiratory and cardiovascular reflexes. Stimulation of portions of the nearby bulbar raphe complex, specifically the raphe magnus (RM), have also been shown to suppress phrenic activity and to decrease blood pressure and heart rate. Since synaptic connectivity between the NGC and the RM has been demonstrated, we hypothesized that the RM may be involved in the cardiopulmonary effects of NGC stimulation. This study found that electrolytic lesions in the raphe magnus attenuated the inhibitory respiratory effects but not the cardiovascular suppression due to NGC stimulation. Lesions in the raphe magnus also lowered resting blood pressure and resting breath frequency. We conclude that the RM may mediate part of the NGC-mediated respiratory effects.

Animal models of respiratory syncytial virus infection and disease

USDA-ARS?s Scientific Manuscript database

The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the ...

Correction of respiratory disorders in a mouse model of Rett syndrome

PubMed Central

Abdala, Ana P. L.; Dutschmann, Mathias; Bissonnette, John M.; Paton, Julian F. R.

2010-01-01

Rett syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene that encodes the transcription factor methyl-CpG-binding protein 2 (MeCP2). A major debilitating phenotype in affected females is frequent apneas, and heterozygous Mecp2-deficient female mice mimic the human respiratory disorder. GABA defects have been demonstrated in the brainstem of Mecp2-deficient mice. Here, using an intact respiratory network, we show that apnea in RTT mice is characterized by excessive excitatory activity in expiratory cranial and spinal nerves. Augmenting GABA markedly improves the respiratory phenotype. In addition, a serotonin 1a receptor agonist that depresses expiratory neuron activity also reduces apnea, corrects the irregular breathing pattern, and prolongs survival in MeCP2 null males. Combining a GABA reuptake blocker with a serotonin 1a agonist in heterozygous females completely corrects their respiratory defects. The results indicate that GABA and serotonin 1a receptor activity are candidates for treatment of the respiratory disorders in Rett syndrome. PMID:20921395

Numerical simulation of volume-controlled mechanical ventilated respiratory system with 2 different lungs.

PubMed

Shi, Yan; Zhang, Bolun; Cai, Maolin; Zhang, Xiaohua Douglas

2017-09-01

Mechanical ventilation is a key therapy for patients who cannot breathe adequately by themselves, and dynamics of mechanical ventilation system is of great significance for life support of patients. Recently, models of mechanical ventilated respiratory system with 1 lung are used to simulate the respiratory system of patients. However, humans have 2 lungs. When the respiratory characteristics of 2 lungs are different, a single-lung model cannot reflect real respiratory system. In this paper, to illustrate dynamic characteristics of mechanical ventilated respiratory system with 2 different lungs, we propose a mathematical model of mechanical ventilated respiratory system with 2 different lungs and conduct experiments to verify the model. Furthermore, we study the dynamics of mechanical ventilated respiratory system with 2 different lungs. This research study can be used for improving the efficiency and safety of volume-controlled mechanical ventilation system. Copyright © 2016 John Wiley & Sons, Ltd.

Long-term air pollution exposure and cardio- respiratory mortality: a review.

PubMed

Hoek, Gerard; Krishnan, Ranjini M; Beelen, Rob; Peters, Annette; Ostro, Bart; Brunekreef, Bert; Kaufman, Joel D

2013-05-28

Current day concentrations of ambient air pollution have been associated with a range of adverse health effects, particularly mortality and morbidity due to cardiovascular and respiratory diseases. In this review, we summarize the evidence from epidemiological studies on long-term exposure to fine and coarse particles, nitrogen dioxide (NO2) and elemental carbon on mortality from all-causes, cardiovascular disease and respiratory disease. We also summarize the findings on potentially susceptible subgroups across studies. We identified studies through a search in the databases Medline and Scopus and previous reviews until January 2013 and performed a meta-analysis if more than five studies were available for the same exposure metric.

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

PubMed Central

Larios Mora, Alejandro; Detalle, Laurent; Van Geelen, Albert; Davis, Michael S.; Stohr, Thomas; Gallup, Jack M.; Ackermann, Mark R.

2015-01-01

Rationale Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. Methods Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 107 FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. Results Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and

CO2 exposure as translational cross-species experimental model for panic

PubMed Central

Leibold, N K; van den Hove, D L A; Viechtbauer, W; Buchanan, G F; Goossens, L; Lange, I; Knuts, I; Lesch, K P; Steinbusch, H W M; Schruers, K R J

2016-01-01

The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral–emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies. PMID:27598969

Cardiovascular Disease Risk Varies by Birth Month in Canines.

PubMed

Boland, Mary Regina; Kraus, Marc S; Dziuk, Eddie; Gelzer, Anna R

2018-05-17

The canine heart is a robust physiological model for the human heart. Recently, birth month associations have been reported and replicated in humans using clinical health records. While animals respond readily to their environment in the wild, a systematic investigation of birth season dependencies among pets and specifically canines remains lacking. We obtained data from the Orthopedic Foundation of Animals on 129,778 canines representing 253 distinct breeds. Among canines that were not predisposed to cardiovascular disease, a clear birth season relationship is observed with peak risk occurring in June-August. Our findings indicate that acquired cardiovascular disease among canines, especially those that are not predisposed to cardiovascular disease, appears birth season dependent. The relative risk of cardiovascular disease for canines not predisposed to cardiovascular disease was as high as 1.47 among July pups. The overall adjusted odds ratio, when mixed breeds were excluded, for the birth season effect was 1.02 (95% CI: 1.002, 1.047, p = 0.032) after adjusting for breed and genetic cardiovascular predisposition effects. Studying birth season effects in model organisms can help to elucidate potential mechanisms behind the reported associations.

Ultrasound investigation of fetal human upper respiratory anatomy.

PubMed

Wolfson, V P; Laitman, J T

1990-07-01

Although the human upper respiratory-upper digestive tract is an area of vital importance, relatively little is known about either the structural or functional changes that occur in the region during the fetal period. While investigations in our laboratory have begun to chart these changes through the use of postmortem materials, in vivo studies have been rarely attempted. This study combines ultrasonography with new applications of video editing to examine aspects of prenatal upper respiratory development. Structures of the fetal upper respiratory-digestive tract and their movements were studied through the use of ultrasonography and detailed frame-by-frame analysis. Twenty-five living fetuses, aged 18-36 weeks gestation, were studied in utero during routine diagnostic ultrasound examination. These real-time linear array sonograms were videotaped during each study. Videotapes were next analyzed for anatomical structures and movement patterns, played back through the ultrasound machine in normal speed, and then examined with a frame-by-frame video editor (FFVE) to identify structures and movements. Still images were photographed directly from the video monitor using a 35 mm camera. Results show that upper respiratory and digestive structures, as well as their movements, could be seen clearly during normal speed and repeat frame-by-frame analysis. Major structures that could be identified in the majority of subjects included trachea in 20 of 25 fetuses (80%); larynx, 76%; pharynx, 76%. Smaller structures were more variable, but were nevertheless observed on both sagittal and coronal section: piriform sinuses, 76%; thyroid cartilage, 36%; cricoid cartilage, 32%; and epiglottis, 16%. Movements of structures could also be seen and were those typically observed in connection with swallowing: fluttering tongue movements, changes in pharyngeal shape, and passage of a bolus via the piriform sinuses to esophagus. Fetal swallows had minimal laryngeal motion. This study

Simulation of Cardiovascular Response to the Head-Up/Head-Down Tilt at Different Angles

NASA Astrophysics Data System (ADS)

Liu, Yang; Lu, Hong-Bing; Jiao, Chun; Zhang, Li-Fan

2008-06-01

The disappearance of hydrostatic pressure is the original factor that causes the changes of cardiovascular system under microgravity. The hydrostatical changes can be simulated by postural changes. Especially the head-down position can be used to simulate the effects of microgravity. The goal of this investigation was to develop a mathematical model for simulation of the human cardiovascular responses to acute and prolonged exposure under microgravity environment. We were particularly interested in the redistribution of transmural pressures, flows, blood volume, and the consequent alterations in local hemodynamics in different cardiovascular compartments during acute exposure and chronic adjustments. As a preliminary study, we first developed a multi-element, distributed hemodynamic model of human cardiovascular system, and verified the model to simulate cardiovascular changes during head up/down tilt at various angles.

DISPOSITION OF MULBERRY POLLEN IN THE HUMAN RESPIRATORY SYSTEMS: A MATHEMATICAL MODEL

EPA Science Inventory

Inhaled particle deposition sites must be identified to effectively treat human airway diseases. e have determined distribution patterns of a selected aeroallergen, mulberry pollen, among human extrathoracic (ET: i.e., oronasopharyngeal) regions and the lung. redictive model vali...

Intensive Care Unit Admission and Death Rates of Infants Admitted With Respiratory Syncytial Virus Lower Respiratory Tract Infection in Mexico.

PubMed

Vizcarra-Ugalde, Sergio; Rico-Hernández, Montserrat; Monjarás-Ávila, César; Bernal-Silva, Sofía; Garrocho-Rangel, Maria E; Ochoa-Pérez, Uciel R; Noyola, Daniel E

2016-11-01

Respiratory syncytial virus (RSV) is the most common etiology for acute respiratory infection hospital admissions in young children. Case fatality rates for hospitalized patients range between 0% and 3.4%. Recent reports indicate that deaths associated with RSV are uncommon in developed countries. However, the role of this virus as a current cause of mortality in other countries requires further examination. Children with RSV infection admitted between May 2003 and December 2014 to a level 2 specialty hospital in Mexico were included in this analysis. Underlying risk factors, admission to the intensive care unit (ICU) and condition on discharge were assessed to determine the ICU admission and death rates associated to RSV infection. We analyzed data of 1153 patients with RSV infection in whom information regarding underlying illnesses and discharge status was available. Sixty patients (5.2 %) were admitted to the ICU and 12 (1.04 %) died. Relevant underlying conditions were present in 320 (27.7%) patients. Infants with underlying respiratory disorders (excluding asthma) and a history of prematurity had high ICU admission rates (17.1% and 13.8%, respectively). Mortality rates were highest for infants with respiratory disease (excluding asthma) (7.3%), cardiovascular diseases (5.9%) and neurologic disorders (5.3%). The ICU admission and death rates were higher in infants <6 months of age than in other age groups. The ICU admission rate and mortality rate in Mexican infants hospitalized with RSV infection were 5.2% and 1%, respectively. Mortality rates were high in infants with respiratory, cardiovascular and neurologic disorders.

A new theoretical framework for modeling respiratory protection based on the beta distribution.

PubMed

Klausner, Ziv; Fattal, Eyal

2014-08-01

The problem of modeling respiratory protection is well known and has been dealt with extensively in the literature. Often the efficiency of respiratory protection is quantified in terms of penetration, defined as the proportion of an ambient contaminant concentration that penetrates the respiratory protection equipment. Typically, the penetration modeling framework in the literature is based on the assumption that penetration measurements follow the lognormal distribution. However, the analysis in this study leads to the conclusion that the lognormal assumption is not always valid, making it less adequate for analyzing respiratory protection measurements. This work presents a formulation of the problem from first principles, leading to a stochastic differential equation whose solution is the probability density function of the beta distribution. The data of respiratory protection experiments were reexamined, and indeed the beta distribution was found to provide the data a better fit than the lognormal. We conclude with a suggestion for a new theoretical framework for modeling respiratory protection. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Environmental and anthropogenic factors affecting the respiratory toxicity of volcanic ash in vitro

NASA Astrophysics Data System (ADS)

Tomašek, Ines; Horwell, Claire J.; Damby, David E.; Ayris, Paul M.; Barošová, Hana; Geers, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara; Clift, Martin J. D.

2016-04-01

Human exposure to inhalable volcanic ash particles following an eruption is a health concern, as respirable-sized particles can potentially contribute towards adverse respiratory health effects, such as the onset or exacerbation of respiratory and cardiovascular diseases. Although there is substantial information on the mineralogical properties of volcanic ash that may influence its biological reactivity, knowledge as to how external factors, such as air pollution, contribute to and augment the potential reactivity is limited. To determine the respiratory effects of volcanic particle interactions with anthropogenic pollution and volcanic gases we will experimentally assess: (i) physicochemical characteristics of volcanic ash relevant to respiratory toxicity; (ii) the effects of simultaneously inhaling anthropogenic pollution (i.e. diesel exhaust particles (DEP)) and volcanic ash (of different origins); (iii) alteration of volcanic ash toxicity following interaction with volcanic gases. In order to gain a first understanding of the biological impact of the respirable fraction of volcanic ash when inhaled with DEP in vitro, we used a sophisticated 3D triple cell co-culture model of the human alveolar epithelial tissue barrier. The multi-cellular system was exposed to DEP [0.02 mg/mL] and then exposed to either a single or repeated dose of well-characterised respirable volcanic ash (0.26 ± 0.09 or 0.89 ± 0.29 μg/cm2, respectively) from the Soufrière Hills volcano, Montserrat for a period of 24 hours using a pseudo-air liquid interface approach. Cultures were subsequently assessed for adverse biological endpoints including cytotoxicity, oxidative stress and (pro)-inflammatory responses. Results indicated that the combination of DEP and respirable volcanic ash at sub-lethal concentrations incited a significant release of pro-inflammatory markers that was greater than the response for either DEP or volcanic ash, independently. Further work is planned, to determine if

A Pulsatile Cardiovascular Computer Model for Teaching Heart-Blood Vessel Interaction.

ERIC Educational Resources Information Center

Campbell, Kenneth; And Others

1982-01-01

Describes a model which gives realistic predictions of pulsatile pressure, flow, and volume events in the cardiovascular system. Includes computer oriented laboratory exercises for veterinary and graduate students; equations of the dynamic and algebraic models; and a flow chart for the cardiovascular teaching program. (JN)

Space physiology IV: mathematical modeling of the cardiovascular system in space exploration.

PubMed

Keith Sharp, M; Batzel, Jerry Joseph; Montani, Jean-Pierre

2013-08-01

Mathematical modeling represents an important tool for analyzing cardiovascular function during spaceflight. This review describes how modeling of the cardiovascular system can contribute to space life science research and illustrates this process via modeling efforts to study postflight orthostatic intolerance (POI), a key issue for spaceflight. Examining this application also provides a context for considering broader applications of modeling techniques to the challenges of bioastronautics. POI, which affects a large fraction of astronauts in stand tests upon return to Earth, presents as dizziness, fainting and other symptoms, which can diminish crew performance and cause safety hazards. POI on the Moon or Mars could be more critical. In the field of bioastronautics, POI has been the dominant application of cardiovascular modeling for more than a decade, and a number of mechanisms for POI have been investigated. Modeling approaches include computational models with a range of incorporated factors and hemodynamic sophistication, and also physical models tested in parabolic and orbital flight. Mathematical methods such as parameter sensitivity analysis can help identify key system mechanisms. In the case of POI, this could lead to more effective countermeasures. Validation is a persistent issue in modeling efforts, and key considerations and needs for experimental data to synergistically improve understanding of cardiovascular responses are outlined. Future directions in cardiovascular modeling include subject-specific assessment of system status, as well as research on integrated physiological responses, leading, for instance, to assessment of subject-specific susceptibility to POI or effects of cardiovascular alterations on muscular, vision and cognitive function.

Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study.

PubMed

Khaw, Kay-Tee; Luben, Robert; Wareham, Nicholas

2014-11-01

Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain. We examined the prospective relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality by the cause and incident diseases in a prospective population study. Serum vitamin D concentrations were measured in 14,641 men and women aged 42-82 y in 1997-2000 who were living in Norfolk, United Kingdom, and were followed up to 2012. Participants were categorized into 5 groups according to baseline serum concentrations of total 25(OH)D <30, 30 to <50, 50 to <70, 70 to <90, and ≥ 90 nmol/L. The mean serum total 25(OH)D was 56.6 nmol/L, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs (95% CIs) for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). When analyzed as a continuous variable and with additional adjustment for body mass index, smoking, social class, education, physical activity, alcohol intake, plasma vitamin C, history of cardiovascular disease, diabetes, or cancer, HRs for a 20-nmol/L increase in 25(OH)D were 0.92 (0.88, 0.96) (P < 0.001) for total mortality, 0.96 (0.93, 0.99) (P = 0.014) (4469 events) for cardiovascular disease, 0.89 (0.85, 0.93) (P < 0.0001) (2132 events) for respiratory disease, 0.89 (0.81, 0.98) (P = 0.012) (563 events) for fractures, and 1.02 (0.99, 1.06) (P = 0.21) (3121 events) for incident total cancers. Plasma 25(OH)D concentrations predict subsequent lower 13-y total mortality and incident cardiovascular disease, respiratory disease, and fractures but not total incident cancers. For mortality, lowest risks were in subjects with concentrations >90 nmol/L, and there was no evidence of increased mortality at high concentrations, suggesting that a moderate

In Vitro and in Silico Tools To Assess Extent of Cellular Uptake and Lysosomal Sequestration of Respiratory Drugs in Human Alveolar Macrophages.

PubMed

Ufuk, Ayşe; Assmus, Frauke; Francis, Laura; Plumb, Jonathan; Damian, Valeriu; Gertz, Michael; Houston, J Brian; Galetin, Aleksandra

2017-04-03

Accumulation of respiratory drugs in human alveolar macrophages (AMs) has not been extensively studied in vitro and in silico despite its potential impact on therapeutic efficacy and/or occurrence of phospholipidosis. The current study aims to characterize the accumulation and subcellular distribution of drugs with respiratory indication in human AMs and to develop an in silico mechanistic AM model to predict lysosomal accumulation of investigated drugs. The data set included 9 drugs previously investigated in rat AM cell line NR8383. Cell-to-unbound medium concentration ratio (K p,cell ) of all drugs (5 μM) was determined to assess the magnitude of intracellular accumulation. The extent of lysosomal sequestration in freshly isolated human AMs from multiple donors (n = 5) was investigated for clarithromycin and imipramine (positive control) using an indirect in vitro method (±20 mM ammonium chloride, NH 4 Cl). The AM cell parameters and drug physicochemical data were collated to develop an in silico mechanistic AM model. Three in silico models differing in their description of drug membrane partitioning were evaluated; model (1) relied on octanol-water partitioning of drugs, model (2) used in vitro data to account for this process, and model (3) predicted membrane partitioning by incorporating AM phospholipid fractions. In vitro K p,cell ranged >200-fold for respiratory drugs, with the highest accumulation seen for clarithromycin. A good agreement in K p,cell was observed between human AMs and NR8383 (2.45-fold bias), highlighting NR8383 as a potentially useful in vitro surrogate tool to characterize drug accumulation in AMs. The mean K p,cell of clarithromycin (81, CV = 51%) and imipramine (963, CV = 54%) were reduced in the presence of NH 4 Cl by up to 67% and 81%, respectively, suggesting substantial contribution of lysosomal sequestration and intracellular binding in the accumulation of these drugs in human AMs. The in vitro data showed variability in drug

Human Bocavirus in Korean Children with Gastroenteritis and Respiratory Tract Infections.

PubMed

Lee, Eun Jin; Kim, Han-Sung; Kim, Hyun Soo; Kim, Jae-Seok; Song, Wonkeun; Kim, MiYoung; Lee, Young Kyung; Kang, Hee Jung

2016-01-01

Human bocaviruses (HBoVs) are suggested to be etiologic agents of childhood respiratory and gastrointestinal infections. There are four main recognized genotypes of HBoVs (HBoV1-4); the HBoV-1 genotype is considered to be the primary etiologic agent in respiratory infections, whereas the HBoV2-4 genotypes have been mainly associated with gastrointestinal infections. The aim of the present study was to determine the distribution of HBoV genotypes in children with respiratory or gastrointestinal infections in a hospital in Korea. A total of 662 nasopharyngeal swabs (NPSs) and 155 fecal specimens were collected from children aged 5 years or less. Polymerase chain reaction (PCR) was conducted to detect the NS1 HBoV gene. The VP1 gene of HBoV was further amplified in samples that were positive for the NS1 gene. The PCR products of VP1 gene amplification were genotyped by sequence analysis. HBoV was detected in 69 (14.5%) of 662 NPSs and in 10 (6.5%) of 155 fecal specimens. Thirty-three isolates from NPSs and five isolates from fecal specimens were genotyped, and all 38 sequenced isolates were identified as the HBoV-1 genotype. HBoV-1 is the most prevalent genotype in children with respiratory or gastrointestinal HBoV infections in a hospital in Korea.

Human Bocavirus in Korean Children with Gastroenteritis and Respiratory Tract Infections

PubMed Central

Lee, Eun Jin; Kim, Jae-Seok; Song, Wonkeun; Kim, MiYoung; Lee, Young Kyung

2016-01-01

Human bocaviruses (HBoVs) are suggested to be etiologic agents of childhood respiratory and gastrointestinal infections. There are four main recognized genotypes of HBoVs (HBoV1–4); the HBoV-1 genotype is considered to be the primary etiologic agent in respiratory infections, whereas the HBoV2–4 genotypes have been mainly associated with gastrointestinal infections. The aim of the present study was to determine the distribution of HBoV genotypes in children with respiratory or gastrointestinal infections in a hospital in Korea. A total of 662 nasopharyngeal swabs (NPSs) and 155 fecal specimens were collected from children aged 5 years or less. Polymerase chain reaction (PCR) was conducted to detect the NS1 HBoV gene. The VP1 gene of HBoV was further amplified in samples that were positive for the NS1 gene. The PCR products of VP1 gene amplification were genotyped by sequence analysis. HBoV was detected in 69 (14.5%) of 662 NPSs and in 10 (6.5%) of 155 fecal specimens. Thirty-three isolates from NPSs and five isolates from fecal specimens were genotyped, and all 38 sequenced isolates were identified as the HBoV-1 genotype. HBoV-1 is the most prevalent genotype in children with respiratory or gastrointestinal HBoV infections in a hospital in Korea. PMID:27990436

Mitochondria and Cardiovascular Aging

PubMed Central

Dai, Dao-Fu; Ungvari, Zoltan

2013-01-01

Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

Extracorporeal Respiratory Support With a Miniature Integrated Pediatric Pump-Lung Device in an Acute Ovine Respiratory Failure Model.

PubMed

Wei, Xufeng; Sanchez, Pablo G; Liu, Yang; Claire Watkins, A; Li, Tieluo; Griffith, Bartley P; Wu, Zhongjun J

2016-11-01

Respiratory failure is one of the major causes of mortality and morbidity all over the world. Therapeutic options to treat respiratory failure remain limited. The objective of this study was to evaluate the gas transfer performance of a newly developed miniature portable integrated pediatric pump-lung device (PediPL) with small membrane surface for respiratory support in an acute ovine respiratory failure model. The respiratory failure was created in six adult sheep using intravenous anesthesia and reduced mechanical ventilation at 2 breaths/min. The PediPL device was surgically implanted and evaluated for respiratory support in a venovenous configuration between the right atrium and pulmonary artery. The hemodynamics and respiratory status of the animals during support with the device gas transfer performance of the PediPL were studied for 4 h. The animals exhibited respiratory failure 30 min after mechanical ventilation was reduced to 2 breaths/min, indicated by low oxygen partial pressure, low oxygen saturation, and elevated carbon dioxide in arterial blood. The failure was reversed by establishing respiratory support with the PediPL after 30 min. The rates of O 2 transfer and CO 2 removal of the PediPL were 86.8 and 139.1 mL/min, respectively. The results demonstrated that the PediPL (miniature integrated pump-oxygenator) has the potential to provide respiratory support as a novel treatment for both hypoxia and hypercarbia. The compact size of the PediPL could allow portability and potentially be used in many emergency settings to rescue patients suffering acute lung injury. Copyright © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

A compartment model of alveolar-capillary oxygen diffusion with ventilation-perfusion gradient and dynamics of air transport through the respiratory tract.

PubMed

Jaworski, Jacek; Redlarski, Grzegorz

2014-08-01

This paper presents a model of alveolar-capillary oxygen diffusion with dynamics of air transport through the respiratory tract. For this purpose electrical model representing the respiratory tract mechanics and differential equations representing oxygen membrane diffusion are combined. Relevant thermodynamic relations describing the mass of oxygen transported into the human body are proposed as the connection between these models, as well as the influence of ventilation-perfusion mismatch on the oxygen diffusion. The model is verified based on simulation results of varying exercise intensities and statistical calculations of the results obtained during various clinical trials. The benefit of the approach proposed is its application in simulation-based research aimed to generate quantitative data of normal and pathological conditions. Based on the model presented, taking into account many essential physiological processes and air transport dynamics, comprehensive and combined studies of the respiratory efficiency can be performed. The impact of physical exercise, precise changes in respiratory tract mechanics and alterations in breathing pattern can be analyzed together with the impact of various changes in alveolar-capillary oxygen diffusion. This may be useful in simulation of effects of many severe medical conditions and increased activity level. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets.

PubMed

Satterfield, Benjamin A; Cross, Robert W; Fenton, Karla A; Borisevich, Viktoriya; Agans, Krystle N; Deer, Daniel J; Graber, Jessica; Basler, Christopher F; Geisbert, Thomas W; Mire, Chad E

2016-07-15

Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological

Estrogen in cardiovascular disease during systemic lupus erythematosus.

PubMed

Gilbert, Emily L; Ryan, Michael J

2014-12-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against cardiovascular risk factors in

Estrogen in Cardiovascular Disease during Systemic Lupus Erythematosus

PubMed Central

Gilbert, Emily L.; Ryan, Michael J.

2015-01-01

Purpose Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. Methods PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. Findings The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against

Bridging the gap between measurements and modelling: a cardiovascular functional avatar.

PubMed

Casas, Belén; Lantz, Jonas; Viola, Federica; Cedersund, Gunnar; Bolger, Ann F; Carlhäll, Carl-Johan; Karlsson, Matts; Ebbers, Tino

2017-07-24

Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements.

Towards understanding the complexity of cardiovascular oscillations: Insights from information theory.

PubMed

Javorka, Michal; Krohova, Jana; Czippelova, Barbora; Turianikova, Zuzana; Lazarova, Zuzana; Wiszt, Radovan; Faes, Luca

2018-07-01

Cardiovascular complexity is a feature of healthy physiological regulation, which stems from the simultaneous activity of several cardiovascular reflexes and other non-reflex physiological mechanisms. It is manifested in the rich dynamics characterizing the spontaneous heart rate and blood pressure variability (HRV and BPV). The present study faces the challenge of disclosing the origin of short-term HRV and BPV from the statistical perspective offered by information theory. To dissect the physiological mechanisms giving rise to cardiovascular complexity in different conditions, measures of predictive information, information storage, information transfer and information modification were applied to the beat-to-beat variability of heart period (HP), systolic arterial pressure (SAP) and respiratory volume signal recorded non-invasively in 61 healthy young subjects at supine rest and during head-up tilt (HUT) and mental arithmetics (MA). Information decomposition enabled to assess simultaneously several expected and newly inferred physiological phenomena, including: (i) the decreased complexity of HP during HUT and the increased complexity of SAP during MA; (ii) the suppressed cardiorespiratory information transfer, related to weakened respiratory sinus arrhythmia, under both challenges; (iii) the altered balance of the information transferred along the two arms of the cardiovascular loop during HUT, with larger baroreflex involvement and smaller feedforward mechanical effects; and (iv) an increased importance of direct respiratory effects on SAP during HUT, and on both HP and SAP during MA. We demonstrate that a decomposition of the information contained in cardiovascular oscillations can reveal subtle changes in system dynamics and improve our understanding of the complexity changes during physiological challenges. Copyright © 2018. Published by Elsevier Ltd.

Circadian misalignment increases cardiovascular disease risk factors in humans

PubMed Central

Morris, Christopher J.; Purvis, Taylor E.; Hu, Kun; Scheer, Frank A. J. L.

2016-01-01

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk. PMID:26858430

TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS

EPA Science Inventory

TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS. Zhe Zhang*, Huawei Shi, Clement Kleinstreuer, Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910; Chong S. Kim, National Health and En...

Respiratory-gated electrical impedance tomography: a potential technique for quantifying stroke volume

NASA Astrophysics Data System (ADS)

Arshad, Saaid H.; Murphy, Ethan K.; Halter, Ryan J.

2016-03-01

Telemonitoring is becoming increasingly important as the proportion of the population living with cardiovascular disease (CVD) increases. Currently used health parameters in the suite of telemonitoring tools lack the sensitivity and specificity to accurately predict heart failure events, forcing physicians to play a reactive versus proactive role in patient care. A novel cardiac output (CO) monitoring device is proposed that leverages a custom smart phone application and a wearable electrical impedance tomography (EIT) system. The purpose of this work is to explore the potential of using respiratory-gated EIT to quantify stroke volume (SV) and assess its feasibility using real data. Simulations were carried out using the 4D XCAT model to create anatomically realistic meshes and electrical conductivity profiles representing the human thorax and the intrathoracic tissue. A single 5-second period respiration cycle with chest/lung expansion was modeled with end-diastole (ED) and end-systole (ES) heart volumes to evaluate how effective EIT-based conductivity changes represent clinically significant differences in SV. After establishing a correlation between conductivity changes and SV, the applicability of the respiratory-gated EIT was refined using data from the PhysioNet database to estimate the number of useful end-diastole (ED) and end-systole (ES) heart events attained over a 3.3 minute period. The area associated with conductivity changes was found to correlate to SV with a correlation coefficient of 0.92. A window of 12.5% around peak exhalation was found to be the optimal phase of the respiratory cycle from which to record EIT data. Within this window, ~47 useable ED and ES were found with a standard deviation of 28 using 3.3 minutes of data for 20 patients.

Coconut oil consumption and cardiovascular risk factors in humans

PubMed Central

Eyres, Michael F.; Chisholm, Alexandra; Brown, Rachel C.

2016-01-01

Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease. PMID:26946252

Smog exposure and host resistance to respiratory pathogens

EPA Science Inventory

The US EPA is evaluating the health effects of photochemical smog on respiratory, cardiovascular and metabolic health (https://www.epa.gov/air-research/secondary-organic-aerosol-soas-research). Smog exposure has been associated with an increased risk of allergy and decreased res...

Wildland fire smoke and human health.

PubMed

Cascio, Wayne E

2018-05-15

The natural cycle of landscape fire maintains the ecological health of the land, yet adverse health effects associated with exposure to emissions from wildfire produce public health and clinical challenges. Systematic reviews conclude that a positive association exists between exposure to wildfire smoke or wildfire particulate matter (PM 2.5 ) and all-cause mortality and respiratory morbidity. Respiratory morbidity includes asthma, chronic obstructive pulmonary disease (COPD), bronchitis and pneumonia. The epidemiological data linking wildfire smoke exposure to cardiovascular mortality and morbidity is mixed, and inconclusive. More studies are needed to define the risk for common and costly clinical cardiovascular outcomes. Susceptible populations include people with respiratory and possibly cardiovascular diseases, middle-aged and older adults, children, pregnant women and the fetus. The increasing frequency of large wildland fires, the expansion of the wildland-urban interface, the area between unoccupied land and human development; and an increasing and aging U.S. population are increasing the number of people at-risk from wildfire smoke, thus highlighting the necessity for broadening stakeholder cooperation to address the health effects of wildfire. While much is known, many questions remain and require further population-based, clinical and occupational health research. Health effects measured over much wider geographical areas and for longer periods time will better define the risk for adverse health outcomes, identify the sensitive populations and assess the influence of social factors on the relationship between exposure and health outcomes. Improving exposure models and access to large clinical databases foreshadow improved risk analysis facilitating more effective risk management. Fuel and smoke management remains an important component for protecting population health. Improved smoke forecasting and translation of environmental health science into

Existence of periodic solutions in a model of respiratory syncytial virus RSV

NASA Astrophysics Data System (ADS)

Arenas, Abraham J.; González, Gilberto; Jódar, Lucas

2008-08-01

In this paper we study the existence of a positive periodic solutions for nested models of respiratory syncytial virus RSV, by using a continuation theorem based on coincidence degree theory. Conditions for the existence of periodic solutions in the model are given. Numerical simulations related to the transmission of respiratory syncytial virus in Madrid and Rio Janeiro are included.

Respiratory modulation of human autonomic rhythms

NASA Technical Reports Server (NTRS)

Badra, L. J.; Cooke, W. H.; Hoag, J. B.; Crossman, A. A.; Kuusela, T. A.; Tahvanainen, K. U.; Eckberg, D. L.

2001-01-01

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.

MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

PubMed

Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

2013-11-01

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

Contemporary model for cardiovascular risk prediction in people with type 2 diabetes.

PubMed

Kengne, Andre Pascal; Patel, Anushka; Marre, Michel; Travert, Florence; Lievre, Michel; Zoungas, Sophia; Chalmers, John; Colagiuri, Stephen; Grobbee, Diederick E; Hamet, Pavel; Heller, Simon; Neal, Bruce; Woodward, Mark

2011-06-01

Existing cardiovascular risk prediction equations perform non-optimally in different populations with diabetes. Thus, there is a continuing need to develop new equations that will reliably estimate cardiovascular disease (CVD) risk and offer flexibility for adaptation in various settings. This report presents a contemporary model for predicting cardiovascular risk in people with type 2 diabetes mellitus. A 4.5-year follow-up of the Action in Diabetes and Vascular disease: preterax and diamicron-MR controlled evaluation (ADVANCE) cohort was used to estimate coefficients for significant predictors of CVD using Cox models. Similar Cox models were used to fit the 4-year risk of CVD in 7168 participants without previous CVD. The model's applicability was tested on the same sample and another dataset. A total of 473 major cardiovascular events were recorded during follow-up. Age at diagnosis, known duration of diabetes, sex, pulse pressure, treated hypertension, atrial fibrillation, retinopathy, HbA1c, urinary albumin/creatinine ratio and non-HDL cholesterol at baseline were significant predictors of cardiovascular events. The model developed using these predictors displayed an acceptable discrimination (c-statistic: 0.70) and good calibration during internal validation. The external applicability of the model was tested on an independent cohort of individuals with type 2 diabetes, where similar discrimination was demonstrated (c-statistic: 0.69). Major cardiovascular events in contemporary populations with type 2 diabetes can be predicted on the basis of routinely measured clinical and biological variables. The model presented here can be used to quantify risk and guide the intensity of treatment in people with diabetes.

Household air pollution: a call for studies into biomarkers of exposure and predictors of respiratory disease.

PubMed

Rylance, Jamie; Gordon, Stephen B; Naeher, Luke P; Patel, Archana; Balmes, John R; Adetona, Olorunfemi; Rogalsky, Derek K; Martin, William J

2013-05-01

Household air pollution (HAP) from indoor burning of biomass or coal is a leading global cause of morbidity and mortality, mostly due to its association with acute respiratory infection in children and chronic respiratory and cardiovascular diseases in adults. Interventions that have significantly reduced exposure to HAP improve health outcomes and may reduce mortality. However, we lack robust, specific, and field-ready biomarkers to identify populations at greatest risk and to monitor the effectiveness of interventions. New scientific approaches are urgently needed to develop biomarkers of human exposure that accurately reflect exposure or effect. In this Perspective, we describe the global need for such biomarkers, the aims of biomarker development, and the state of development of tests that have the potential for rapid transition from laboratory bench to field use.

A novel swine model of ricin-induced acute respiratory distress syndrome.

PubMed

Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Sabo, Tamar; Kronman, Chanoch

2017-02-01

Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. © 2017. Published by The Company of Biologists Ltd.

A novel swine model of ricin-induced acute respiratory distress syndrome

PubMed Central

Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Kronman, Chanoch

2017-01-01

ABSTRACT Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. PMID:28067630

Effect of Sustained Human Centrifugation on Autonomic Cardiovascular and Vestibular Function

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Benavides, Edgar W.; Harm, Deborah L.; Rupert, A. H.

2002-01-01

Repeated exposure to +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, both sustained exposure to +Gx and changes in otolith function resulting from the gravitational changes of space flight and parabolic flight may adversely affect autonomic cardiovascular function and orthostatic tolerance. HYPOTHESES: Baroreflex function and orthostatic tolerance are acutely improved by a single sustained (30 min) exposure to +3Gz but not +3Gx. Moreover, after 30 min of +3Gx, any changes that occur in autonomic cardiovascular function will relate commensurately to changes in otolith function. METHODS: Twenty-two healthy human subjects were first exposed to 5 min of +3 Gz centrifugation and then subsequently up to a total of30 min of either +3Gz (n = 15) or +3Gx (n = 7) centrifugation. Tests of autonomic cardiovascular function both before and after both types of centrifugation included: (a) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; (b) carotid-cardiac baroreflex tests; ( c) Valsalva tests; and (d) 30-min head-up tilt (HUT) tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: All four +3Gz subjects who were intolerant to HUT before centrifugation became tolerant to HUT after centrifugation. The operational point of the carotid-cardiac baroreflex and the Valsalva-related baroreflex were also enhanced in the +3Gz group but not in the +3Gx group. No significant vestibular-autonomic relationships were detected, other than a significant vestibular-cerebrovascular interaction reported previously. CONCLUSIONS: A single, sustained exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance whereas a similar exposure to +3 Gx centrifugation appears to have less effect.

The Evolution of Respiratory Cryptosporidiosis: Evidence for Transmission by Inhalation

PubMed Central

Sponseller, Jerlyn K.; Griffiths, Jeffrey K.

2014-01-01

SUMMARY The protozoan parasite Cryptosporidium infects all major vertebrate groups and causes significant diarrhea in humans, with a spectrum of diseases ranging from asymptomatic to life-threatening. Children and immunodeficient individuals are disproportionately affected, especially in developing countries, where cryptosporidiosis contributes substantially to morbidity and mortality in preschool-age children. Despite the enormous disease burden from cryptosporidiosis, no antiprotozoal agent or vaccine exists for effective treatment or prevention. Cryptosporidiosis involving the respiratory tract has been described for avian species and mammals, including immunocompromised humans. Recent evidence indicates that respiratory cryptosporidiosis may occur commonly in immunocompetent children with cryptosporidial diarrhea and unexplained cough. Findings from animal models, human case reports, and a few epidemiological studies suggest that Cryptosporidium may be transmitted via respiratory secretions, in addition to the more recognized fecal-oral route. It is postulated that transmission of Cryptosporidium oocysts may occur by inhalation of aerosolized droplets or by contact with fomites contaminated by coughing. Delineating the role of the respiratory tract in disease transmission may provide necessary evidence to establish further guidelines for prevention of cryptosporidiosis. PMID:24982322

Medical waste tissues - breathing life back into respiratory research.

PubMed

BéruBé, Kelly A

2013-12-01

With the advent of biobanks to store human lung cells and tissues from patient donations and from the procurement of medical waste tissues, it is now possible to integrate (both spatially and temporally) cells into anatomically-correct and physiologically-functional tissues. Modern inhalation toxicology relies on human data on exposure and adverse effects, to determine the most appropriate risk assessments and mitigations for beneficial respiratory health. A point in case is the recapitulation of airway tissue, such as the bronchial epithelium, to investigate the impact of air pollution on human respiratory health. The bronchi are the first point of contact for inhaled substances that bypass defences in the upper respiratory tract. Animal models have been used to resolve such inhalation toxicology hazards. However, the access to medical waste tissues has enabled the Lung Particle Research Group to tissue-engineer the Micro-Lung (TM) and Metabo-Lung(TM) cell culture models, as alternatives to animals in basic research and in the safety testing of aerosolised consumer goods. The former model favours investigations focused on lung injury and repair mechanisms, and the latter model provides the element of metabolism, through the co-culturing of lung and liver (hepatocyte) cells. These innovations represent examples of the animal-free alternatives advocated by the 21st century toxicology paradigm, whereby human-derived cell/tissue data will lead to more-accurate and more-reliable public health risk assessments and therapeutic mitigations (e.g. exposure to ambient air pollutants and adverse drug reactions) for lung disease. 2013 FRAME.

Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study.

PubMed

García-García, María Luz; Calvo, Cristina; Rey, Cristina; Díaz, Beatriz; Molinero, Maria Del Mar; Pozo, Francisco; Casas, Inmaculada

2017-01-01

Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children's mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p <0.05). There were many differences in seasonality and clinical characteristics between HMPV and other respiratory viruses being more similar to HRSV. HMPV infections accounted for 5.5% of total viral infections in hospitalized children. The clinical characteristics were similar to HRSV infections, but seasonality and clinical data were different from other viral infections.

Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative human physiology.

PubMed

MacKay, Christina M; Skow, Rachel J; Tymko, Michael M; Boulet, Lindsey M; Davenport, Margie H; Steinback, Craig D; Ainslie, Philip N; Lemieux, Chantelle C M; Day, Trevor A

2016-03-01

One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The "Duffin" hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2 and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination (R(2)), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology. Copyright © 2016 The American Physiological Society.

Iterative integral parameter identification of a respiratory mechanics model.

PubMed

Schranz, Christoph; Docherty, Paul D; Chiew, Yeong Shiong; Möller, Knut; Chase, J Geoffrey

2012-07-18

Patient-specific respiratory mechanics models can support the evaluation of optimal lung protective ventilator settings during ventilation therapy. Clinical application requires that the individual's model parameter values must be identified with information available at the bedside. Multiple linear regression or gradient-based parameter identification methods are highly sensitive to noise and initial parameter estimates. Thus, they are difficult to apply at the bedside to support therapeutic decisions. An iterative integral parameter identification method is applied to a second order respiratory mechanics model. The method is compared to the commonly used regression methods and error-mapping approaches using simulated and clinical data. The clinical potential of the method was evaluated on data from 13 Acute Respiratory Distress Syndrome (ARDS) patients. The iterative integral method converged to error minima 350 times faster than the Simplex Search Method using simulation data sets and 50 times faster using clinical data sets. Established regression methods reported erroneous results due to sensitivity to noise. In contrast, the iterative integral method was effective independent of initial parameter estimations, and converged successfully in each case tested. These investigations reveal that the iterative integral method is beneficial with respect to computing time, operator independence and robustness, and thus applicable at the bedside for this clinical application.

Subclinical cardiovascular damage and fat utilization in overweight/obese individuals receiving the same dietary and pharmacological interventions.

PubMed

Montalcini, Tiziana; Lamprinoudi, Theodora; Gorgone, Gaetano; Ferro, Yvelise; Romeo, Stefano; Pujia, Arturo

2014-12-01

Subclinical organ damage precedes the occurrence of cardiovascular events in individuals with obesity and hypertension. The aim of this study was to assess the relationship between fuel utilization and subclinical cardiovascular damage in overweight/obese individuals free of established cardiovascular disease receiving the same diet and pharmacological intervention. In this retrospective study a total of 35 subjects following a balanced diet were enrolled. They underwent a complete nutritional and cardiovascular assessment. Echocardiography and ultrasonography of the carotid arteries was performed. The respiratory quotient (fuel utilization index) was assessed by indirect calorimetry. A total of 18 had left ventricular concentric remodeling, 17 were normal. Between these two groups, a significant difference of intima-media thickness was showed (p = 0.015). Also a difference of respiratory quotient was shown with the highest value in those with remodeling (p = 0.038). At univariate and multivariate analysis, cardiac remodeling was associated with respiratory quotient (RQ) (p = 0.04; beta = 0.38; SE = 0.021; B = 0.044). The area under the receiver operating characteristic (ROC) curve for respiratory quotient to predict remodeling was 0.72 (SE = 0.093; p = 0.031; RQ = 0.87; 72% sensitivity, 84% specificity). The respiratory quotient is significantly different between those participants with and without cardiac remodeling. Its measurement may help for interpreting the (patho)physiological mechanisms in the nutrients utilization of obese people with different response to dietary or pharmacological interventions.

Modeling of Cardiovascular Response to Weightlessness

NASA Technical Reports Server (NTRS)

Sharp, M. Keith

1999-01-01

pressure and, to a limited extent, in extravascular and pedcardial hydrostatic pressure were investigated. A complete hydraulic model of the cardiovascular system was built and flown aboard the NASA KC-135 and a computer model was developed and tested in simulated microgravity. Results obtained with these models have confirmed that a simple lack of hydrostatic pressure within an artificial ventricle causes a decrease in stroke volume. When combined with the acute increase in ventricular pressure associated with the elimination of hydrostatic pressure within the vasculature and the resultant cephalad fluid shift with the models in the upright position, however, stroke volume increased in the models. Imposition of a decreased pedcardial pressure in the computer model and in a simplified hydraulic model increased stroke volume. Physiologic regional fluid shifting was also demonstrated by the models. The unifying parameter characterizing of cardiac response was diastolic ventricular transmural pressure (DVDELTAP) The elimination of intraventricular hydrostatic pressure in O-G decreased DVDELTAP stroke volume, while the elimination of intravascular hydrostatic pressure increased DVDELTAP and stroke volume in the upright posture, but reduced DVDELTAP and stroke volume in the launch posture. The release of gravity on the chest wall and its associated influence on intrathoracic pressure, simulated by a drop in extraventricular pressure4, increased DVDELTAP ans stroke volume.