WorldWideScience

Sample records for model human respiratory

  1. A Review on Human Respiratory Modeling.

    Science.gov (United States)

    Ghafarian, Pardis; Jamaati, Hamidreza; Hashemian, Seyed Mohammadreza

    2016-01-01

    Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article.

  2. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  3. Computational 3-D Model of the Human Respiratory System

    Science.gov (United States)

    We are developing a comprehensive, morphologically-realistic computational model of the human respiratory system that can be used to study the inhalation, deposition, and clearance of contaminants, while being adaptable for age, race, gender, and health/disease status. The model ...

  4. 3-D Model of the Human Respiratory System

    Science.gov (United States)

    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, ethn...

  5. A Novel Parametric Model For The Human Respiratory System

    Directory of Open Access Journals (Sweden)

    Clara Mihaela IONESCU

    2003-12-01

    Full Text Available The purpose of this work is to present some recent results in an ongoing research project between Ghent University and Chess Medical Technology Company Belgium. The overall aim of the project is to provide a fast method for identification of the human respiratory system in order to allow for an instantaneously diagnosis of the patient by the medical staff. A novel parametric model of the human respiratory system as well as the obtained experimental results is presented in this paper. A prototype apparatus developed by the company, based on the forced oscillation technique is used to record experimental data from 4 patients in this paper. Signal processing is based on spectral analysis and is followed by the parametric identification of a non-linear mechanistic model. The parametric model is equivalent to the structure of a simple electrical RLC-circuit, containing a non-linear capacitor. These parameters have a useful and easy-to-interpret physical meaning for the medical staff members.

  6. Velocity profiles in idealized model of human respiratory tract

    Directory of Open Access Journals (Sweden)

    Jicha M.

    2013-04-01

    Full Text Available This article deals with numerical simulation focused on velocity profiles in idealized model of human upper airways during steady inspiration. Three r gimes of breathing were investigated: Resting condition, Deep breathing and Light activity which correspond to most common regimes used for experiments and simulations. Calculation was validated with experimental data given by Phase Doppler Anemometry performed on the model with same geometry. This comparison was made in multiple points which form one cross-section in trachea near first bifurcation of bronchial tree. Development of velocity profile in trachea during steady inspiration was discussed with respect for common phenomenon formed in trachea and for future research of transport of aerosol particles in human respiratory tract.

  7. Mathematical modelling of a human external respiratory system

    Science.gov (United States)

    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.

  8. A new approach to modeling of selected human respiratory system diseases, directed to computer simulations.

    Science.gov (United States)

    Redlarski, Grzegorz; Jaworski, Jacek

    2013-10-01

    This paper presents a new versatile approach to model severe human respiratory diseases via computer simulation. The proposed approach enables one to predict the time histories of various diseases via information accessible in medical publications. This knowledge is useful to bioengineers involved in the design and construction of medical devices that are employed for monitoring of respiratory condition. The approach provides the data that are crucial for testing diagnostic systems. This can be achieved without the necessity of probing the physiological details of the respiratory system as well as without identification of parameters that are based on measurement data. © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  10. The human respiratory gate

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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, ethn...

  12. Studying human respiratory disease in animals--role of induced and naturally occurring models.

    Science.gov (United States)

    Williams, Kurt; Roman, Jesse

    2016-01-01

    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. A Two-Dimensional Human Minilung System (Model for Respiratory Syncytial Virus Infections

    Directory of Open Access Journals (Sweden)

    Esmeralda Magro-Lopez

    2017-12-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of serious pediatric respiratory diseases that lacks effective vaccine or specific therapeutics. Although our understanding about HRSV biology has dramatically increased during the last decades, the need for adequate models of HRSV infection is compelling. We have generated a two-dimensional minilung from human embryonic stem cells (hESCs. The differentiation protocol yielded at least six types of lung and airway cells, although it is biased toward the generation of distal cells. We show evidence of HRSV replication in lung cells, and the induction of innate and proinflammatory responses, thus supporting its use as a model for the study of HRSV–host interactions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

    2016-09-01

    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 breathing 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

    2016-09-30

    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 conditions 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.

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

    Science.gov (United States)

    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.

  17. Transmission of human respiratory syncytial virus in the immunocompromised ferret model

    NARCIS (Netherlands)

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

    2018-01-01

    textabstractHuman 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

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

    Science.gov (United States)

    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.

  19. Application of morphological and physiological parameters representative of a sample Brazilian population in the human respiratory tract model

    International Nuclear Information System (INIS)

    Reis, A.A.; Cardoso, J.C.S.; Lourenco, M.C.

    2005-01-01

    Full text: The Human Respiratory Tract Model (HRTM) proposed in ICRP Publication 66 account for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. These changing characteristics can influence the rates and the sites of deposition. Concerning the respiratory physiological parameters the breathing characteristics influence the volume, the inhalation rate of air and the portion that enters through the nose and the mouth. These characteristics are important to determine the fractional deposition. The HRTM model uses morphological and physiological parameters from the Caucasian man to establish deposition fractions in the respiratory tract regions. lt is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends for a reliable evaluation of the regional deposition the use of parameters from a local population when information is available. The main purpose of this study is to verify the influence in using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of ICRP Publication 66. The morphological and physiological data were obtained from the literature. The software EXCEL for Windows (version 2000) was used in order to implement the deposition model and also to allow the changes in parameters of interest. Initially, the implemented model was checked using the parameters defined in ICRP and the results of the fraction deposition in the respiratory tract compartments were compared. Finally, morphological and physiological parameters from Brazilian adult male were applied and the fractional deposition calculated. The respiratory values at different levels of activity for ages varying from

  20. Human Respiratory Syncytial Virus and Human Metapneumovirus

    OpenAIRE

    Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns

    2009-01-01

    The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...

  1. COMPARATIVE COMPUTATIONAL MODELING OF AIRFLOWS AND VAPOR DOSIMETY IN THE RESPIRATORY TRACTS OF RAT, MONKEY, AND HUMAN

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Minard, Kevin R.; Jacob, Rick E.; Timchalk, Charles; Glenny, Robb W.; Pipavath, Sudhaker; Cox, Timothy C.; Wallis, Chris; Larson, Richard; Fanucchi, M.; Postlewait, Ed; Einstein, Daniel R.

    2012-07-01

    Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is 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. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomic region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.

  2. Human Respiratory Syncytial Virus and Human Metapneumovirus

    Directory of Open Access Journals (Sweden)

    Luciana Helena Antoniassi da Silva

    2009-08-01

    Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms.  The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.

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

    Science.gov (United States)

    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.

  4. BIOLOGY OF HUMAN RESPIRATORY SYNCYTIAL VIRUS: A ...

    African Journals Online (AJOL)

    DR. AMINU

    information about its biology which may be useful to the present and future researchers. Key words: Respiratory virus, Human Respiratory syncytial virus, biology, genome, epidemiology, immunity. INTRODUCTION. Acute lower ..... of respiratory infections in bone marrow transplant. Pneumonia develops in about one-half of ...

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

    Science.gov (United States)

    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.

  6. Innovative characteristics of the new dosimetric model for the human respiratory tract studied by the ICRP appointed Task Group of Committee 2

    CERN Document Server

    Melandri, C; Tarroni, G

    1991-01-01

    In 1984, the ICRP appointed a Task Group of Committee 2 to review and revise, as necessary, the current lung dosimetric model. On the basis of the knowledge acquired during the past 20 years, the Task Group's approach has been to review, in depth, the morphology and physiology of the human respiratory tract, inspirability of aerosols and regional deposition of inhaled particles as functions of aerosol size and breathing parameters, clearance of deposited materials, nature and specific sites of damage to the respiratory system caused by inhaled radioactive substances. In the proposed model, clearance from the three regions of the respiratory tract (extrathoracic ET, fast-clearing thoracic T sub f and slow-clearing thoracic T sub s , comprising lymph nodes) is described in terms of competition between the mechanical processes moving particles, which do not depend on the substances, and those of absorption into the blood, determined solely by the material. A Task Group report will also include models for calcula...

  7. Application of the physiological and morphological parameters of the brazilian population sample to the mathematical model of the human respiratory tract

    International Nuclear Information System (INIS)

    Reis, Arlene Alves dos

    2005-01-01

    The Human Respiratory Tract Model proposed by the ICRP Publication 66 accounts for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. Concerning the respiratory physiological parameters the breathing characteristics influence the volume, the inhalation rate of air and the portion that enters through the nose and the mouth. These characteristics are important to determine the fractional deposition. The model uses morphological and physiological parameters from the Caucasian man to establish deposition fractions in the respiratory tract regions. It is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends, for a reliable evaluation of the regional deposition, the use of parameters from a local population when information is available. The main purpose of this study is to verify the influence in using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of the ICRP Publication 66. The morphological and physiological data were obtained from the literature. The software EXCEL for Windows (version 2000) was used in order to implement the deposition model and also to allow the changes in parameters of interest. Initially, the implemented model was checked using the parameters defined by the ICRP and the results of the fraction deposition in the respiratory tract compartments were compared. Finally, morphological and physiological parameters from Brazilian adult male were applied and the fractional deposition calculated. The results suggest a significant variation in fractional deposition when Brazilian parameters are applied in the model. (author)

  8. A multi-compartment model for slow bronchial clearance of insoluble particles - Extension of the ICRP human respiratory tract models

    International Nuclear Information System (INIS)

    Sturm, R.; Hofmann, W.

    2006-01-01

    To incorporate the various mechanisms that are presently assumed to be responsible for the experimentally observed slow bronchial clearance into the HRTM, a multi-compartment model was developed to simulate the clearance of insoluble particles in the tracheobronchial tree of the human lung. The new model considers specific mass transfer paths that may play an important role for slow bronchial clearance. These include the accumulation of particulate mass in the peri-ciliary sol layer, phagocytosis of stored particles by airway macrophages and uptake of deposited mass by epithelial cells. Besides the gel layer representing fast mucociliary clearance, all cellular and non-cellular units involved in the slow clearance process are described by respective compartments that are connected by specific transfer rates. The gastrointestinal tract and lymph nodes are included into the model as final accumulation compartments, to which mass is transferred via the airway route and the transepithelial path. Predicted retention curves correspond well with previously published data. (authors)

  9. Innovative characteristics of the new dosimetric model for the human respiratory tract studied by the ICRP appointed Task Group of Committee 2

    International Nuclear Information System (INIS)

    Melandri, C.; Battisti, P.; Tarroni, G.

    1991-02-01

    In 1984, the ICRP appointed a Task Group of Committee 2 to review and revise, as necessary, the current lung dosimetric model. On the basis of the knowledge acquired during the past 20 years, the Task Group's approach has been to review, in depth, the morphology and physiology of the human respiratory tract, inspirability of aerosols and regional deposition of inhaled particles as functions of aerosol size and breathing parameters, clearance of deposited materials, nature and specific sites of damage to the respiratory system caused by inhaled radioactive substances. In the proposed model, clearance from the three regions of the respiratory tract (extrathoracic ET, fast-clearing thoracic T f and slow-clearing thoracic T s , comprising lymph nodes) is described in terms of competition between the mechanical processes moving particles, which do not depend on the substances, and those of absorption into the blood, determined solely by the material. A Task Group report will also include models for calculating radiation doses to tissues of the respiratory system following inhalation of α, β and γ emitting particulate and gaseous radionuclides. (author)

  10. Computational Fluid and Particle Dynamics in the Human Respiratory System

    CERN Document Server

    Tu, Jiyuan; Ahmadi, Goodarz

    2013-01-01

    Traditional research methodologies in the human respiratory system have always been challenging due to their invasive nature. Recent advances in medical imaging and computational fluid dynamics (CFD) have accelerated this research. This book compiles and details recent advances in the modelling of the respiratory system for researchers, engineers, scientists, and health practitioners. It breaks down the complexities of this field and provides both students and scientists with an introduction and starting point to the physiology of the respiratory system, fluid dynamics and advanced CFD modeling tools. In addition to a brief introduction to the physics of the respiratory system and an overview of computational methods, the book contains best-practice guidelines for establishing high-quality computational models and simulations. Inspiration for new simulations can be gained through innovative case studies as well as hands-on practice using pre-made computational code. Last but not least, students and researcher...

  11. Respiratory trace deposition models. Final report

    International Nuclear Information System (INIS)

    Yeh, H.C.

    1980-03-01

    Respiratory tract characteristics of four mammalian species (human, dog, rat and Syrian hamster) were studied, using replica lung casts. An in situ casting techniques was developed for making the casts. Based on an idealized branch model, over 38,000 records of airway segment diameters, lengths, branching angles and gravity angles were obtained from measurements of two humans, two Beagle dogs, two rats and one Syrian hamster. From examination of the trimmed casts and morphometric data, it appeared that the structure of the human airway is closer to a dichotomous structure, whereas for dog, rat and hamster, it is monopodial. Flow velocity in the trachea and major bronchi in living Beagle dogs was measured using an implanted, subminiaturized, heated film anemometer. A physical model was developed to simulate the regional deposition characteristics proposed by the Task Group on Lung Dynamics of the ICRP. Various simulation modules for the nasopharyngeal (NP), tracheobronchial (TB) and pulmonary (P) compartments were designed and tested. Three types of monodisperse aerosols were developed for animal inhalation studies. Fifty Syrian hamsters and 50 rats were exposed to five different sizes of monodisperse fused aluminosilicate particles labeled with 169 Yb. Anatomical lung models were developed for four species (human, Beagle dog, rat and Syrian hamster) that were based on detailed morphometric measurements of replica lung casts. Emphasis was placed on developing a lobar typical-path lung model and on developing a modeling technique which could be applied to various mammalian species. A set of particle deposition equations for deposition caused by inertial impaction, sedimentation, and diffusion were developed. Theoretical models of particle deposition were developed based on these equations and on the anatomical lung models

  12. Modeling Respiratory Toxicity of Authentic Lunar Dust

    Science.gov (United States)

    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.

  13. Human Metapneumovirus and Respiratory Syncytial Virus Disease in Children, Yemen

    Science.gov (United States)

    Al-Sonboli, Najla; Hart, Charles A.; Al-Aghbari, Nasher; Al-Ansi, Ahmed; Ashoor, Omar

    2006-01-01

    Factors increasing the severity of respiratory infections in developing countries are poorly described. We report factors associated with severe acute respiratory illness in Yemeni children (266 infected with respiratory syncytial virus and 66 with human metapneumovirus). Age, indoor air pollution, and incomplete vaccinations were risk factors and differed from those in industrialized countries. PMID:17073098

  14. Conditional reprogramming of pediatric airway epithelial cells: A new human model to investigate early-life respiratory disorders.

    Science.gov (United States)

    Wolf, S; Perez, G F; Mukharesh, L; Isaza, N; Preciado, D; Freishtat, R J; Pillai, D; Rose, M C; Nino, G

    2017-12-01

    Airway epithelial cells (AEC) are quite difficult to access in newborns and infants. It is critically important to develop robust life-extended models to conduct translational studies in this age group. We propose the use of a recently described cell culture technology (conditionally reprogrammed cells-CRC) to generate continuous primary cell cultures from nasal and bronchial AEC of young children. We collected nasal and/or bronchial AEC from a total of 23 subjects of different ages including newborns/infants/toddlers (0-2 years; N = 9), school-age children (4-11 years; N = 6), and a group of adolescent/adult donors (N = 8). For CRC generation, we used conditioned medium from mitotically inactivated 3T3 fibroblasts and Rho-associated kinase (ROCK) inhibitor (Y-27632). Antiviral immune responses were studied using 25 key antiviral genes and protein production of type III epithelial interferon (IFN λ1) after double-stranded (ds) RNA exposure. CRC derived from primary AEC of neonates/infants and young children exhibited: (i) augmented proliferative capacity and life extension, (ii) preserved airway epithelial phenotype after multiple passages, (iii) robust immune responses characterized by the expression of innate antiviral genes and parallel nasal/bronchial production of IFN λ1 after exposure to dsRNA, and (iv) induction of airway epithelial inflammatory and remodeling responses to dsRNA (eg, CXCL8 and MMP9). Conditional reprogramming of AEC from young children is a feasible and powerful translational approach to investigate early-life airway epithelial immune responses in humans. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  15. Traffic aerosol lobar doses deposited in the human respiratory system.

    Science.gov (United States)

    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 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.

  16. Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Henrik Larsen, Hans; Koch, Anders

    2004-01-01

    The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p respiratory support. hMPV is present in young...

  17. Mucosal inflammation at the respiratory interface: a zebrafish model.

    Science.gov (United States)

    Progatzky, Fränze; Cook, H Terence; Lamb, Jonathan R; Bugeon, Laurence; Dallman, Margaret J

    2016-03-15

    Inflammatory diseases of the respiratory system such as asthma and chronic obstructive pulmonary disease are increasing globally and remain poorly understood conditions. Although attention has long focused on the activation of type 1 and type 2 helper T cells of the adaptive immune system in these diseases, it is becoming increasingly apparent that there is also a need to understand the contributions and interactions between innate immune cells and the epithelial lining of the respiratory system. Cigarette smoke predisposes the respiratory tissue to a higher incidence of inflammatory disease, and here we have used zebrafish gills as a model to study the effect of cigarette smoke on the respiratory epithelium. Zebrafish gills fulfill the same gas-exchange function as the mammalian airways and have a similar structure. Exposure to cigarette smoke extracts resulted in an increase in transcripts of the proinflammatory cytokines TNF-α, IL-1β, and MMP9 in the gill tissue, which was at least in part mediated via NF-κB activation. Longer term exposure of fish for 6 wk to cigarette smoke extract resulted in marked structural changes to the gills with lamellar fusion and mucus cell formation, while signs of inflammation or fibrosis were absent. This shows, for the first time, that zebrafish gills are a relevant model for studying the effect of inflammatory stimuli on a respiratory epithelium, since they mimic the immunopathology involved in respiratory inflammatory diseases of humans. Copyright © 2016 the American Physiological Society.

  18. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus

    NARCIS (Netherlands)

    Gaunt, Eleanor R.; Jansen, Rogier R.; Poovorawan, Yong; Templeton, Kate E.; Toms, Geoffrey L.; Simmonds, Peter

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  19. Molecular Epidemiology and Evolution of Human Respiratory Syncytial Virus and Human Metapneumovirus

    NARCIS (Netherlands)

    Gaunt, E.R.; Jansen, R.R.; Poovorawan, Y.; Templeton, K.E.; Toms, G.L.; Simmonds, P.

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  20. Application of the physiological and morphological parameters of the brazilian population sample to the mathematical model of the human respiratory tract; Aplicacao dos parametros fisiologicos e morfologicos de uma amostra da populacao brasileira no modelo matematico do trato respiratorio humano

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Arlene Alves dos

    2005-07-01

    The Human Respiratory Tract Model proposed by the ICRP Publication 66 accounts for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. Concerning the respiratory physiological parameters the breathing characteristics influence the volume, the inhalation rate of air and the portion that enters through the nose and the mouth. These characteristics are important to determine the fractional deposition. The model uses morphological and physiological parameters from the Caucasian man to establish deposition fractions in the respiratory tract regions. It is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends, for a reliable evaluation of the regional deposition, the use of parameters from a local population when information is available. The main purpose of this study is to verify the influence in using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of the ICRP Publication 66. The morphological and physiological data were obtained from the literature. The software EXCEL for Windows (version 2000) was used in order to implement the deposition model and also to allow the changes in parameters of interest. Initially, the implemented model was checked using the parameters defined by the ICRP and the results of the fraction deposition in the respiratory tract compartments were compared. Finally, morphological and physiological parameters from Brazilian adult male were applied and the fractional deposition calculated. The results suggest a significant variation in fractional deposition when Brazilian parameters are applied in the model. (author)

  1. 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.

    Science.gov (United States)

    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

    2018-02-15

    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

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

    Science.gov (United States)

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

    2018-01-05

    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 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.

  3. Biophysical Modeling of Respiratory Organ Motion

    Science.gov (United States)

    Werner, René

    Methods to estimate respiratory organ motion can be divided into two groups: biophysical modeling and image registration. In image registration, motion fields are directly extracted from 4D ({D}+{t}) image sequences, often without concerning knowledge about anatomy and physiology in detail. In contrast, biophysical approaches aim at identification of anatomical and physiological aspects of breathing dynamics that are to be modeled. In the context of radiation therapy, biophysical modeling of respiratory organ motion commonly refers to the framework of continuum mechanics and elasticity theory, respectively. Underlying ideas and corresponding boundary value problems of those approaches are described in this chapter, along with a brief comparison to image registration-based motion field estimation.

  4. Human respiratory considerations for civil transport aircraft oxygen system.

    Science.gov (United States)

    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...

  5. Dynamics of human respiratory system mycoflora

    Directory of Open Access Journals (Sweden)

    Anna Biedunkiewicz

    2014-08-01

    Full Text Available The study aimed at determing the prevalence of individual species of fungi in the respiratory systems of women and men, analysis of the dynamics of the fungi in individual sections of the respiratory system as concerns their quantity and identification of phenology of the isolated fungi coupled with an attempt at identifying their possible preferences for appearing during specific seasons of thc year. During 10 years of studies (1989- 1998. 29 species of fungi belonging: Candida, Geolrichum, Saccharomyces, Saccharomycopsis, Schizosaccharomyces, Torulopsis, Trichosporon and Aspergillus were isolated from the ontocenoses of the respiratory systems of patients at the Independent Public Center for Pulmonology and Oncology in Olsztyn. Candida albicans was a clearly dominating fungus. Individual species appeared individually, in twos or threes in a single patient, they were isolated more frequently in the spring and autumn, less frequently during the winter and summer. The largest number of fungi species were isolated from sputum (29 species, bronchoscopic material (23 species and pharyngeal swabs (15 species. Sacchoromycopsis capsularis and Trichosporon beigelii should be treated as new for the respiratory system. Biodiversity of fungi, their numbers and continous fluctuations in frequency indicate that the respiratory system ontocenose offers the optimum conditions for growth and development of the majority of the majority of yeasts - like fungi.

  6. A validated hybrid computational fluid dynamics-physiologically based pharmacokinetic model for respiratory tract vapor absorption in the human and rat and its application to inhalation dosimetry of diacetyl.

    Science.gov (United States)

    Gloede, Eric; Cichocki, Joseph A; Baldino, Joshua B; Morris, John B

    2011-09-01

    Diacetyl vapor is associated with bronchiolar injury in man but primarily large airway injury in the rat. The goal of this study was to develop a physiologically based pharmacokinetic model for inspired vapor dosimetry and to apply the model to diacetyl. The respiratory tract was modeled as a series of airways: nose, trachea, main bronchi, large bronchi, small bronchi, bronchioles, and alveoli with tissue dimensions obtained from the literature. Airborne vapor was allowed to absorb (or desorb) from tissues based on mass transfer coefficients. Transfer of vapor within tissues was based on molecular diffusivity with direct reaction with tissue substrates and/or metabolism being allowed in each tissue compartment. In vitro studies were performed to provide measures of diacetyl metabolism kinetics and direct reaction rates allowing for the development of a model with no unassigned variables. Respiratory tract uptake of halothane, acetone, ethanol and diacetyl was measured in male F344 rat to obtain data for model validation. The human model was validated against published values for inspired vapor uptake. For both the human and rat models, a close concordance of model estimates with experimental measurements was observed, validating the model. The model estimates that limited amounts of inspired diacetyl penetrate to the bronchioles of the rat (<2%), whereas in the lightly exercising human, 24% penetration to the bronchioles is estimated. Bronchiolar tissue concentrations of diacetyl in the human are estimated to exceed those in the rat by 40-fold. These inhalation dosimetric differences may contribute to the human-rat differences in diacetyl-induced airway injury.

  7. Respiratory

    Science.gov (United States)

    The words "respiratory" and "respiration" refer to the lungs and breathing. ... Boron WF. Organization of the respiratory system. In: Boron WF, Boulpaep EL, eds. Medical Physiology . 3rd ed. Philadelphia, PA: Elsevier; 2017:chap 26.

  8. Tetratrichomonads from the oral cavity and respiratory tract of humans

    Czech Academy of Sciences Publication Activity Database

    Kutišová, K.; Kulda, J.; Čepička, I.; Flegr, J.; Koudela, Břetislav; Teras, J.; Tachezy, J.

    2005-01-01

    Roč. 131, č. 1 (2005), s. 1-11 ISSN 0031-1820 Grant - others:Grantová agentura Karlovy univerzity v Praze(CZ) 264/1999 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tetratrichomonas spp. * human respiratory tract * oral cavity Subject RIV: EE - Microbiology, Virology Impact factor: 1.703, year: 2005

  9. Epidemiology and clinical associations of human parechovirus respiratory infections

    NARCIS (Netherlands)

    Harvala, H.; Robertson, I.; Leitch, E. C. McWilliam; Benschop, K.; Wolthers, K. C.; Templeton, K.; Simmonds, P.

    2008-01-01

    Infections with human parechoviruses (HPeVs) are prevalent in young children and have been associated with mild gastroenteritis and, less frequently, with meningitis and neonatal sepsis. To investigate the involvement of these viruses in respiratory disease, a highly sensitive nested PCR was used to

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

    Science.gov (United States)

    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.

  11. Respiratory muscle dysfunction in animal models of hypoxic disease: antioxidant therapy goes from strength to strength

    Directory of Open Access Journals (Sweden)

    O'Halloran KD

    2017-07-01

    Full Text Available Ken D O’Halloran,1 Philip Lewis2 1Department of Physiology, School of Medicine, University College Cork, Cork, Ireland; 2Institute and Policlinic for Occupational Medicine, Environmental Medicine and Preventative Research, University Hospital of Cologne, Germany Abstract: The striated muscles of breathing play a critical role in respiratory homeostasis governing blood oxygenation and pH regulation. Upper airway dilator and thoracic pump muscles retain a remarkable capacity for plasticity throughout life, both in health and disease states. Hypoxia, whatever the cause, is a potent driver of respiratory muscle remodeling with evidence of adaptive and maladaptive outcomes for system performance. The pattern, duration, and intensity of hypoxia are key determinants of respiratory muscle structural-, metabolic-, and functional responses and adaptation. Age and sex also influence respiratory muscle tolerance of hypoxia. Redox stress emerges as the principal protagonist driving respiratory muscle malady in rodent models of hypoxic disease. There is a growing body of evidence demonstrating that antioxidant intervention alleviates hypoxia-induced respiratory muscle dysfunction, and that N-acetyl cysteine, approved for use in humans, is highly effective in preventing hypoxia-induced respiratory muscle weakness and fatigue. We posit that oxygen homeostasis is a key driver of respiratory muscle form and function. Hypoxic stress is likely a major contributor to respiratory muscle malaise in diseases of the lungs and respiratory control network. Animal studies provide an evidence base in strong support of the need to explore adjunctive antioxidant therapies for muscle dysfunction in human respiratory disease. Keywords: respiratory muscle, diaphragm, upper airway, hypoxia, antioxidants, N-acetyl-cysteine, OSA, COPD

  12. Human Parechovirus in Respiratory Specimens from Children in Kansas City, Missouri

    OpenAIRE

    Sharp, Justin; Bell, Jeremiah; Harrison, Christopher J.; Nix, W. Allan; Oberste, M. Steven; Selvarangan, Rangaraj

    2012-01-01

    We detected a 3% prevalence rate for human parechovirus (HPeV) in 720 respiratory specimens collected from 637 children seen in our hospital in 2009. Fifteen of 20 were HPeV-3 and two were HPeV-1. Only nonspecific, modest respiratory symptoms were evident in patients with detectable HPeV in respiratory specimens. Seven patients had concurrent respiratory and central nervous system (CNS) HPeV-3 infection, suggesting a possible respiratory route of acquisition.

  13. Computational Models and Emergent Properties of Respiratory Neural Networks

    Science.gov (United States)

    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

  14. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus.

    Directory of Open Access Journals (Sweden)

    Eleanor R Gaunt

    2011-03-01

    Full Text Available Human respiratory syncytial virus (HRSV and human metapneumovirus (HMPV are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F protein, and the extremely diverse attachment (G glycoprotein. Both viruses comprise two genetic groups, A and B. Circulation frequencies of the two genetic groups fluctuate for both viruses, giving rise to frequently observed switching of the predominantly circulating group. Nucleotide sequence data for the F and G gene regions of HRSV and HMPV variants from the UK, The Netherlands, Bangkok and data available from Genbank were used to identify clades of both viruses. Several contemporary circulating clades of HRSV and HMPV were identified by phylogenetic reconstructions. The molecular epidemiology and evolutionary dynamics of clades were modelled in parallel. Times of origin were determined and positively selected sites were identified. Sustained circulation of contemporary clades of both viruses for decades and their global dissemination demonstrated that switching of the predominant genetic group did not arise through the emergence of novel lineages each respiratory season, but through the fluctuating circulation frequencies of pre-existing lineages which undergo proliferative and eclipse phases. An abundance of sites were identified as positively selected within the G protein but not the F protein of both viruses. For HRSV, these were discordant with previously identified residues under selection, suggesting the virus can evade immune responses by generating diversity at multiple sites within linear epitopes. For both viruses, different sites were identified as positively selected between genetic groups.

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

    Science.gov (United States)

    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}

  16. High-throughput gene expression analysis in pigs as model for respiratory infections

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Brogaard, Louise; Schou, Kirstine Klitgaard

    for disease and inflammation. Pigs are fully susceptible to human influenza, and have been demonstrated to be involved in influenza evolution and ecology. Pigs share many similarities with humans regarding lung physiology and innate immune cell infiltration of the respiratory system and thus seem...... to be an obvious large animal model for respiratory infections. This study aimed at providing a better understanding of the involvement of circulating non-coding RNA and innate immune factors in porcine blood leukocytes during influenza virus infection. By employing the pig as a model we were able to perform...

  17. Biology of human respiratory syncytial virus: a review | Aliyu | Bayero ...

    African Journals Online (AJOL)

    Acute lower respiratory tract infection is one of the major causes of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) is the single most important viral cause of lower respiratory tract infection during infancy and early childhood worldwide. Respiratory syncytial virus belongs to the ...

  18. Reference respiratory waveforms by minimum jerk model analysis

    Energy Technology Data Exchange (ETDEWEB)

    Anetai, Yusuke, E-mail: anetai@radonc.med.osaka-u.ac.jp; Sumida, Iori; Takahashi, Yutaka; Yagi, Masashi; Mizuno, Hirokazu; Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita-shi, Osaka 565-0871 (Japan); Ota, Seiichi [Department of Medical Technology, Osaka University Hospital, Yamadaoka 2-15, Suita-shi, Osaka 565-0871 (Japan)

    2015-09-15

    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 minimum 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 discrepancy

  19. Numerical Simulation of Hemodynamic and Physiological Responses of Human Cardiovascular and Respiratory System under Drugs Administration

    Czech Academy of Sciences Publication Activity Database

    Převorovská, Světlana; Maršík, František

    2004-01-01

    Roč. 4, č. 4 (2004), s. 295-304 ISSN 1567-8822 R&D Projects: GA ČR(CZ) GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z2076919 Keywords : human cardiovascular and respiratory system * baroreflex and chemoreflex control * physiologically based pharmacokinetic model Subject RIV: BK - Fluid Dynamics

  20. Numerical simulation of inhaled aerosol particle deposition within 3D realistic human upper respiratory tract

    Science.gov (United States)

    Lin, J.; Fan, J. R.; Zheng, Y. Q.; Hu, G. L.; Pan, D.

    2010-03-01

    Computational fluid dynamics (CFD) simulations of airflow and particle deposition in the upper respiratory tract (URT) were conducted in this paper. Based on the CT (Computerized Tomography) scanned images of a 19-years-old healthy boy, a realistic geometric model of URT from oral cavity to the upper six-generation bronchial is rebuilt. To investigate airflow and particle deposition in the obtained realistic human upper respiratory tract, RNG k-ɛ turbulence model was used to describe the primary flow and particle deposition under three breathing intensity such as 15 L/min, 30 L/min and 60 L/min. The particle is tracked and analyzed in the Lagrangian frame. The velocity fields of airflow under different airflow rates were computed and discussed. In order to study the characteristics of particles movement and the effect of particles diameter on the deposition pattern, eleven kinds of sphere particles with different diameters are selected as research object. The diameters of selected particles as follows: 0.1 μm, 0.5 μm, 1 μm, 2.5 μm, 3 μm, 3.5 μm, 4 μm, 4.5 μm, 5 μm, 6.5 μm and 8 μm. The variation of inhalable particles deposition in realistic human upper respiratory tract with respiratory intensity and particle size was researched and compared. Furthermore, the more real inhalable particles with Rosin-Rammler mass distribution are used to study the effect of particles size. The deposition rate of particles with the different diameter scope in the different part of upper respiratory tract was summarized. The geometrical model based images technology promises to provide more real results of airflow field and particle deposition in the URT.

  1. Computational Breakthrough of Natural Lead Hits from the Genus ofArisaemaagainst Human Respiratory Syncytial Virus.

    Science.gov (United States)

    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.

  2. Respiratory compensation to a primary metabolic alkalosis in humans.

    Science.gov (United States)

    Feldman, Mark; Alvarez, Naiara M; Trevino, Michael; Weinstein, Gary L

    2012-11-01

    There is limited and disparate information about the extent of the respiratory compensation (hypoventilation) that occurs in response to a primary metabolic alkalosis in humans. Our aim was to examine the influence of the plasma bicarbonate concentration, the plasma base excess, and the arterial pH on the arterial carbon dioxide tension in 52 adult patients with primary metabolic alkalosis, mostly due to diuretic use or vomiting. Linear regression analysis was used to correlate degrees of alkalosis with arterial carbon dioxide tensions. In this alkalotic cohort, whose arterial plasma bicarbonate averaged 31.6 mEq/l, plasma base excess averaged 7.8 mEq/l, and pH averaged 7.48, both plasma bicarbonate and base excess correlated closely with arterial carbon dioxide tensions (r = 0.97 and 0.96, respectively; p metabolic alkalosis than has been reported in prior smaller studies.

  3. A Bidirectional Coupling Procedure Applied to Multiscale Respiratory Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kuprat, Andrew P.; Kabilan, Senthil; Carson, James P.; Corley, Richard A.; Einstein, Daniel R.

    2013-07-01

    In this study, we present a novel multiscale computational framework for efficiently linking multiple lower-dimensional models describing the distal lung mechanics to imaging-based 3D computational fluid dynamics (CFD) models of the upper pulmonary airways in order to incorporate physiologically appropriate outlet boundary conditions. The framework is an extension of the Modified Newton’s Method with nonlinear Krylov accelerator developed by Carlson and Miller [1, 2, 3]. Our extensions include the retention of subspace information over multiple timesteps, and a special correction at the end of a timestep that allows for corrections to be accepted with verified low residual with as little as a single residual evaluation per timestep on average. In the case of a single residual evaluation per timestep, the method has zero additional computational cost compared to uncoupled or unidirectionally coupled simulations. We expect these enhancements to be generally applicable to other multiscale coupling applications where timestepping occurs. In addition we have developed a “pressure-drop” residual which allows for stable coupling of flows between a 3D incompressible CFD application and another (lower-dimensional) fluid system. We expect this residual to also be useful for coupling non-respiratory incompressible fluid applications, such as multiscale simulations involving blood flow. The lower-dimensional models that are considered in this study are sets of simple ordinary differential equations (ODEs) representing the compliant mechanics of symmetric human pulmonary airway trees. To validate the method, we compare the predictions of hybrid CFD-ODE models against an ODE-only model of pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets of ODEs describing the distal lung to an imaging-based human lung geometry. Boundary conditions in these models consist of atmospheric pressure at the mouth and intrapleural pressure applied to the multiple

  4. A bidirectional coupling procedure applied to multiscale respiratory modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kuprat, A.P., E-mail: andrew.kuprat@pnnl.gov [Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA (United States); Kabilan, S., E-mail: senthil.kabilan@pnnl.gov [Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA (United States); Carson, J.P., E-mail: james.carson@pnnl.gov [Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA (United States); Corley, R.A., E-mail: rick.corley@pnnl.gov [Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA (United States); Einstein, D.R., E-mail: daniel.einstein@pnnl.gov [Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA (United States)

    2013-07-01

    In this study, we present a novel multiscale computational framework for efficiently linking multiple lower-dimensional models describing the distal lung mechanics to imaging-based 3D computational fluid dynamics (CFDs) models of the upper pulmonary airways in order to incorporate physiologically appropriate outlet boundary conditions. The framework is an extension of the modified Newton’s method with nonlinear Krylov accelerator developed by Carlson and Miller [1], Miller [2] and Scott and Fenves [3]. Our extensions include the retention of subspace information over multiple timesteps, and a special correction at the end of a timestep that allows for corrections to be accepted with verified low residual with as little as a single residual evaluation per timestep on average. In the case of a single residual evaluation per timestep, the method has zero additional computational cost compared to uncoupled or unidirectionally coupled simulations. We expect these enhancements to be generally applicable to other multiscale coupling applications where timestepping occurs. In addition we have developed a “pressure-drop” residual which allows for stable coupling of flows between a 3D incompressible CFD application and another (lower-dimensional) fluid system. We expect this residual to also be useful for coupling non-respiratory incompressible fluid applications, such as multiscale simulations involving blood flow. The lower-dimensional models that are considered in this study are sets of simple ordinary differential equations (ODEs) representing the compliant mechanics of symmetric human pulmonary airway trees. To validate the method, we compare the predictions of hybrid CFD–ODE models against an ODE-only model of pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets of ODEs describing the distal lung to an imaging-based human lung geometry. Boundary conditions in these models consist of atmospheric pressure at the mouth and intrapleural

  5. A bidirectional coupling procedure applied to multiscale respiratory modeling

    International Nuclear Information System (INIS)

    Kuprat, A.P.; Kabilan, S.; Carson, J.P.; Corley, R.A.; Einstein, D.R.

    2013-01-01

    In this study, we present a novel multiscale computational framework for efficiently linking multiple lower-dimensional models describing the distal lung mechanics to imaging-based 3D computational fluid dynamics (CFDs) models of the upper pulmonary airways in order to incorporate physiologically appropriate outlet boundary conditions. The framework is an extension of the modified Newton’s method with nonlinear Krylov accelerator developed by Carlson and Miller [1], Miller [2] and Scott and Fenves [3]. Our extensions include the retention of subspace information over multiple timesteps, and a special correction at the end of a timestep that allows for corrections to be accepted with verified low residual with as little as a single residual evaluation per timestep on average. In the case of a single residual evaluation per timestep, the method has zero additional computational cost compared to uncoupled or unidirectionally coupled simulations. We expect these enhancements to be generally applicable to other multiscale coupling applications where timestepping occurs. In addition we have developed a “pressure-drop” residual which allows for stable coupling of flows between a 3D incompressible CFD application and another (lower-dimensional) fluid system. We expect this residual to also be useful for coupling non-respiratory incompressible fluid applications, such as multiscale simulations involving blood flow. The lower-dimensional models that are considered in this study are sets of simple ordinary differential equations (ODEs) representing the compliant mechanics of symmetric human pulmonary airway trees. To validate the method, we compare the predictions of hybrid CFD–ODE models against an ODE-only model of pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets of ODEs describing the distal lung to an imaging-based human lung geometry. Boundary conditions in these models consist of atmospheric pressure at the mouth and intrapleural

  6. An Improved Dynamic Model for the Respiratory Response to Exercise

    Directory of Open Access Journals (Sweden)

    Leidy Y. Serna

    2018-02-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  8. Mathematical modeling of respiratory system mechanics in the newborn lamb.

    Science.gov (United States)

    Le Rolle, Virginie; Samson, Nathalie; Praud, Jean-Paul; Hernández, Alfredo I

    2013-03-01

    In this paper, a mathematical model of the respiratory mechanics is used to reproduce experimental signal waveforms acquired from three newborn lambs. As the main challenge is to determine specific lamb parameters, a sensitivity analysis has been realized to find the most influent parameters, which are identified using an evolutionary algorithm. Results show a close match between experimental and simulated pressure and flow waveforms obtained during spontaneous ventilation and pleural pressure variations acquired during the application of positive pressure, since root mean square errors equal to 0.0119, 0.0052 and 0.0094. The identified parameters were discussed in light of previous knowledge of respiratory mechanics in the newborn.

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

    Science.gov (United States)

    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.

  10. Mitochondrial respiratory efficiency is positively correlated with human sperm motility.

    Science.gov (United States)

    Ferramosca, Alessandra; Provenzano, Sara Pinto; Coppola, Lamberto; Zara, Vincenzo

    2012-04-01

    To correlate sperm mitochondrial respiratory efficiency with variations in sperm motility and with sperm morphologic anomalies. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption carried out in hypotonically-treated sperm cells. A possible relationship among sperm mitochondrial respiratory efficiency, sperm motility, and morphologic anomalies was investigated. Mitochondrial respiratory efficiency was positively correlated with sperm motility and negatively correlated with the percentage of immotile spermatozoa. Moreover, midpiece defects impaired mitochondrial functionality. Our data indicate that an increase in sperm motility requires a parallel increase in mitochondrial respiratory capacity, thereby supporting the fundamental role played by mitochondrial oxidative phosphorylation in sperm motility of normozoospermic subjects. These results are of physiopathological relevance because they suggest that disturbances of sperm mitochondrial function and of energy production could be responsible for asthenozoospermia. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. A Wearable Capacitive Sensor for Monitoring Human Respiratory Rate

    Science.gov (United States)

    Kundu, Subrata Kumar; Kumagai, Shinya; Sasaki, Minoru

    2013-04-01

    Realizing an untethered, low-cost, and comfortably wearable respiratory rate sensor for long-term breathing monitoring application still remains a challenge. In this paper, a conductive-textile-based wearable respiratory rate sensing technique based on the capacitive sensing approach is proposed. The sensing unit consists of two conductive textile electrodes that can be easily fabricated, laminated, and integrated in garments. Respiration cycle is detected by measuring the capacitance of two electrodes placed on the inner anterior and posterior sides of a T-shirt at either the abdomen or chest position. A convenient wearable respiratory sensor setup with a capacitance-to-voltage converter has been devised. Respiratory rate as well as breathing mode can be accurately identified using the designed sensor. The sensor output provides significant information on respiratory flow. The effectiveness of the proposed system for different breathing patterns has been evaluated by experiments.

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

    Science.gov (United States)

    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.

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

    LENUS (Irish Health Repository)

    Judge, Eoin P

    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.

  14. Pharmacologic modeling of primary mitochondrial respiratory chain dysfunction in zebrafish.

    Science.gov (United States)

    Byrnes, James; Ganetzky, Rebecca; Lightfoot, Richard; Tzeng, Michael; Nakamaru-Ogiso, Eiko; Seiler, Christoph; Falk, Marni J

    2017-07-18

    Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology. Here, we characterize four pharmacologic inhibitor models of mitochondrial RC dysfunction in early larval zebrafish, including rotenone (complex I inhibitor), azide (complex IV inhibitor), oligomycin (complex V inhibitor), and chloramphenicol (mitochondrial translation inhibitor that leads to multiple RC complex dysfunction). A range of concentrations and exposure times of each RC inhibitor were systematically evaluated on early larval development, animal survival, integrated behaviors (touch and startle responses), organ physiology (brain death, neurologic tone, heart rate), and fluorescence-based analyses of mitochondrial physiology in zebrafish skeletal muscle. Pharmacologic RC inhibitor effects were validated by spectrophotometric analysis of Complex I, II and IV enzyme activities, or relative quantitation of ATP levels in larvae. Outcomes were prioritized that utilize in vivo animal imaging and quantitative behavioral assessments, as may optimally inform the translational potential of pre-clinical drug screens for future clinical study in human mitochondrial disease subjects. The RC complex inhibitors each delayed early embryo development, with short-term exposures of these three agents or chloramphenicol from 5 to 7 days

  15. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J. B. M.; Bos, A. P.; Lutter, R.; Rossen, J. W. A.; Schuurman, R.

    2006-01-01

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  16. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J B M; Bos, A P; Lutter, R; Rossen, J W A; Schuurman, R

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

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

    Science.gov (United States)

    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

  18. Deterministic and stochastic models for middle east respiratory syndrome (MERS)

    Science.gov (United States)

    Suryani, Dessy Rizki; Zevika, Mona; Nuraini, Nuning

    2018-03-01

    World Health Organization (WHO) data stated that since September 2012, there were 1,733 cases of Middle East Respiratory Syndrome (MERS) with 628 death cases that occurred in 27 countries. MERS was first identified in Saudi Arabia in 2012 and the largest cases of MERS outside Saudi Arabia occurred in South Korea in 2015. MERS is a disease that attacks the respiratory system caused by infection of MERS-CoV. MERS-CoV transmission occurs directly through direct contact between infected individual with non-infected individual or indirectly through contaminated object by the free virus. Suspected, MERS can spread quickly because of the free virus in environment. Mathematical modeling is used to illustrate the transmission of MERS disease using deterministic model and stochastic model. Deterministic model is used to investigate the temporal dynamic from the system to analyze the steady state condition. Stochastic model approach using Continuous Time Markov Chain (CTMC) is used to predict the future states by using random variables. From the models that were built, the threshold value for deterministic models and stochastic models obtained in the same form and the probability of disease extinction can be computed by stochastic model. Simulations for both models using several of different parameters are shown, and the probability of disease extinction will be compared with several initial conditions.

  19. ASSISTED MODELLING OF MOBILE MEDICAL TREATMENT EQUIPMENT, UPPER RESPIRATORY AFFECTIONS

    Directory of Open Access Journals (Sweden)

    GOANTA Adrian Mihai

    2012-09-01

    Full Text Available The paper aims to present some aspects of parametric modelling application in medical engineering, specifically in the design of medical instruments for ENT diseases. The work also contains both stages, how to obtain all parts parametrically and related accessories that are part of a mobile aerosol -generating medical equipment intended for the treatment of the upper respiratory diseases. Also photorealistic visualization capabilities are highlighted with NX Software from Siemens as well as how to obtain the corresponding 2D documentation.

  20. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  1. ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence.

    Science.gov (United States)

    Murphy, Timothy F; Brauer, Aimee L; Johnson, Antoinette; Kirkham, Charmaine

    2016-01-01

    Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens. In the present study, we performed a comprehensive assessment of 19 SBPs of 15 ABC transporter systems in the M. catarrhalis genome by engineering knockout mutants and studying their role in assays that assess mechanisms of infection. The capacity of M. catarrhalis to survive and grow in the nutrient-limited and hostile environment of the human respiratory tract, including intracellular growth, account in part for its virulence. The results show that ABC transporters that mediate uptake of peptides, amino acids, cations and anions play important roles in pathogenesis by enabling M. catarrhalis to 1) grow in nutrient-limited conditions, 2) invade and survive in human respiratory epithelial cells and 3) persist in the lungs in a murine pulmonary clearance model. The knockout mutants of SBPs and ABC transporters showed different patterns of activity in the assay systems, supporting the conclusion that different SBPs and ABC transporters function at different stages in the pathogenesis of infection. These results indicate that ABC transporters are nutritional virulence factors, functioning to enable the survival of M catarrhalis in the diverse microenvironments of the respiratory tract. Based on the role of ABC transporters as virulence factors of M. catarrhalis, these molecules represent potential drug targets to eradicate the organism from the human respiratory tract.

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

    Science.gov (United States)

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

    2018-02-28

    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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. High-throughput Gene Expression Analysis In Pigs As Model For Respiratory Infections

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Brogaard, Louise; Schou, Kirstine Klitgaard

    (WHO). Animal models are essential in understanding the mechanisms involved in human infectious disease and for the development of effective prevention and treatment strategies. It is increasingly realized that large animal models like the pig are exceptionally human like and serve as an excellent...... pleuropneumoniae causes pneumonia in pigs, a disease which is associated with high morbidity and mortality, as well as impaired animal welfare. The rapidly evolving pneumonia is characterized by large areas of lung necrosis resulting from the combined effect of tissue damage caused by the bacteria, and a strong...... model for disease and inflammation. Pigs are fully susceptible to human influenza, and have been demonstrated to be involved in influenza evolution and ecology. Pigs share many similarities with humans regarding lung physiology and innate immune cell infiltration of the respiratory system and thus seem...

  4. Interdisciplinary approaches of transcranial magnetic stimulation applied to a respiratory neuronal circuitry model.

    Directory of Open Access Journals (Sweden)

    Stéphane Vinit

    Full Text Available 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.

  5. The Linear Model Research on Tibetan Six-Character Poetry's Respiratory Signal

    Science.gov (United States)

    Yonghong, Li; Yangrui, Yang; Lei, Guo; Hongzhi, Yu

    In this paper, we studied the Tibetan six-character pomes' respiratory signal during reading from the perspective of the physiological. Main contents include: 1) Selected 40 representative Tibetan six-character and four lines pomes from ldquo; The Love-songs of 6th Dalai Lama Tshang•yangGya•tsho ", and recorded speech sounds, voice and respiratory signals; 2) Designed a set of respiratory signal parameters for the study of poetry; 3) Extracted the relevant parameters of poetry respiratory signal by using the well-established respiratory signal processing platform; 4) Studied the type of breathing pattern, established the linear model of poetry respiratory signal.

  6. Control aspects of the human cardiovascular-respiratory system under a nonconstant workload.

    Science.gov (United States)

    Calderon, Pio Gabrielle B; Habib, Mustafa; Kappel, Franz; de Los Reyes, Aurelio A

    2017-07-01

    The human cardiovascular system (CVS) and respiratory system (RS) work together in order to supply oxygen (O 2 ) and other substrates needed for metabolism and to remove carbon dioxide (CO 2 ). Global and local control mechanisms act on the CVS in order to adjust blood flow to the different parts of the body. This, in turn, affects the RS since the amount of O 2 and CO 2 transported, respectively to and away from the tissues depends on the cardiac output and blood flow in both the systemic and pulmonary circuits of the CVS. Local metabolic control is influenced by local concentrations of blood gases affecting systemic resistance, resulting to vasoconstriction/vasodilation. Thus, the exchange of blood gases demands a tight coordination between blood flow and ventilation of the lungs. In this work, a model of the cardiovascular-respiratory system (CVRS) is considered to obtain an optimal control for time-dependent ergometric workloads by using the Euler-Lagrange formulation of the optimal control problem. The essential controls in the CVRS model are variations in the heart rate and alveolar ventilation through which the central nervous system restricts the arterial partial pressure of CO 2 ( [Formula: see text] ) close to 40  mmHg. Further, penalization terms in the cost functional are included to match the metabolic need for O 2 and the metabolic production of CO 2 with O 2 - and CO 2 -transport by blood. Copyright © 2017. Published by Elsevier Inc.

  7. Computational redesign of human respiratory syncytial virus epitope as therapeutic peptide vaccines against pediatric pneumonia.

    Science.gov (United States)

    Shi, Xiangxiang; Zheng, Jun; Yan, Tingting

    2018-03-02

    Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. Here, the RSV fusion (F) glycoprotein epitope FFL was redesigned based on its complex crystal structure with motavizumab, an mAb drug in development for the prevention of RSV infections, aiming to obtain therapeutic peptide vaccines with high affinity to induce RSV-specific neutralizing antibodies. Computational modeling and analysis found that only a small region covering the helix-turn-helix (HTH) motif of FFL can directly interact with motavizumab and confer stability and specificity to the complex system, while the rest of the epitope primarily serves as a structural scaffold that stabilizes the HTH conformation of motavizumab-binding site. Molecular dynamics simulations revealed a large flexibility and intrinsic disorder for the isolated linear HTH peptide, which would incur a considerable entropy penalty upon binding to motavizumab. In this respect, the FFL epitope was redesigned by truncation, mutation, and cyclization to derive a number of small cyclic peptide immunogens. We also employed in vitro fluorescence-based assays to demonstrate that the linear epitope peptide has no observable affinity to motavizumab, whereas redesigned versions of the peptide can bind with a moderate or high potency. Graphical abstract Computationally modeled complex structure of RSV F glycoprotein with motavizumab and zoom up of the complex binding site.

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

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2018-03-01

    Full Text Available 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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  11. The effects of carbon monoxide on respiratory chemoreflexes in humans

    International Nuclear Information System (INIS)

    Vesely, A.E.; Somogyi, R.B.; Sasano, Hiroshi; Sasano, Nobuko; Fisher, J.A.; Duffin, James

    2004-01-01

    As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of ∼1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide

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

    Science.gov (United States)

    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.

  13. COPD management as a model for all chronic respiratory conditions: report of the 4th Consensus Conference in Respiratory Medicine.

    Science.gov (United States)

    Nardini, Stefano; De Benedetto, Fernando; Sanguinetti, Claudio M; Bellofiore, Salvatore; Carlone, Stefano; Privitera, Salvatore; Sagliocca, Luciano; Tupputi, Emmanuele; Baccarani, Claudio; Caiffa, Gennaro; Calabrese, Maria Consiglia; Capuozzo, Antonio; Cauchi, Salvatore; Conio, Valentina; Coratella, Giuseppe; Crismancich, Franco; Dal Negro, Roberto W; Dellarole, Franco; Delucchi, Maurizio; Favaretti, Carlo; Forte, Silvia; Gallo, Franca Matilde; Giuliano, Riccardo; Grandi, Marco; Grillo, Antonino; Gualano, Maria Rosaria; Guffanti, Enrico; Locicero, Salvatore; Lombardo, Francesco Paolo; Mantero, Marco; Marasso, Roberto; Martino, Laura; Mastroberardino, Michele; Mereu, Carlo; Messina, Roberto; Neri, Margherita; Novelletto, Bruno Franco; Parente, Paolo; Pasquinucci, Sergio; Pistolesi, Massimo; Polverino, Mario; Posca, Agnese; Richeldi, Luca; Roccia, Fernando; Giustini, Ettore Saffi; Salemi, Michelangelo; Santacroce, Salvatore; Schisano, Mario; Schisano, Matteo; Selvi, Eleonora; Silenzi, Andrea; Soverina, Patrizio; Taranto, Claudio; Ugolini, Marta; Visaggi, Piero; Zanasi, Alessandro

    2017-01-01

    Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3-4 November 2016. Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role.

  14. Comparison of old and new ICRP models for respiratory tract dosimetry

    International Nuclear Information System (INIS)

    Boecker, B.B.

    1993-01-01

    This paper examines the historical development and application of respiratory tract dosimetry models by the International Commission for Radiological Protection, ICRP, for health protection from inhaled radioactive aerosols. Three different models are discussed, those that were included in ICRP recommendations published in 1960 and 1979, and the new ICRP Publication 66. Basic features of these models are compared and contrasted. These features include model structure, sites and frequencies of particle deposition, processes and rates of clearance of the deposited material from the respiratory tract, and consideration of the parameters involved in these processes and how various factors can influence these parameters. All three models lead to the calculation of absorbed radiation doses with differing degrees of regional and local specificity. These calculations are achieved using different tools ranging from quick hand calculations to sophisticated computerized modeling approaches. A side-by-side review of these models indicates several important trends in respiratory tract dosimetry models, the most obvious of which is the increased complexity of each new model over the past 30+ years. These increases reflect both the increasing size of the knowledge base derived from studies in laboratory animals and in human subjects and the need for models more broadly applicable for both occupational and environmental exposures. It is likely that future research will be directed to those key aspects of the new model having the largest uncertainties. The detailed design of the new model and its associated software provide excellent means of identifying useful research areas and using the resulting new information in organized and productive ways

  15. Respiratory system

    Science.gov (United States)

    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.

  16. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  17. Ocular tropism of respiratory viruses.

    Science.gov (United States)

    Belser, Jessica A; Rota, Paul A; Tumpey, Terrence M

    2013-03-01

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Carlos Polanco

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  1. Bacterial Topography of the Healthy Human Lower Respiratory Tract

    Directory of Open Access Journals (Sweden)

    Robert P. Dickson

    2017-02-01

    Full Text Available Although culture-independent techniques have refuted lung sterility in health, controversy about contamination during bronchoscope passage through the upper respiratory tract (URT has impeded research progress. We sought to establish whether bronchoscopic sampling accurately reflects the lung microbiome in health and to distinguish between two proposed routes of authentic microbial immigration, (i dispersion along contiguous respiratory mucosa and (ii subclinical microaspiration. During bronchoscopy of eight adult volunteers without lung disease, we performed seven protected specimen brushings (PSB and bilateral bronchoalveolar lavages (BALs per subject. We amplified, sequenced, and analyzed the bacterial 16S rRNA gene V4 regions by using the Illumina MiSeq platform. Rigorous attention was paid to eliminate potential sources of error or contamination, including a randomized processing order and the inclusion and analysis of exhaustive procedural and sequencing control specimens. Indices of mouth-lung immigration (mouth-lung community similarity, bacterial burden, and community richness were all significantly greater in airway and alveolar specimens than in bronchoscope contamination control specimens, indicating minimal evidence of pharyngeal contamination. Ecological indices of mouth-lung immigration peaked at or near the carina, as predicted for a primary immigration route of microaspiration. Bacterial burden, diversity, and mouth-lung similarity were greater in BAL than PSB samples, reflecting differences in the sampled surface areas. (This study has been registered at ClinicalTrials.gov under registration no. NCT02392182.

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

    Science.gov (United States)

    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.

  3. Secretory Expression and Purification of Respiratory Syncytial Virus G and F Proteins in Human Cells.

    Science.gov (United States)

    Jadhao, Samadhan J; Anderson, Larry J

    2016-01-01

    Respiratory syncytial virus (RSV) is one of the leading causes of range of symptoms from mild upper to serious lower respiratory virus infections in infants, immunocompromised individuals, and the elderly. Despite many decades of research and development, a licensed RSV vaccine is not available for use in human. Since the RSV F and G proteins induce neutralizing antibodies and confer protection from infection, they are important for understanding disease and for developing vaccines and access to purified, expressed proteins is important to RSV research and diagnostics. We describe methods to produce recombinant RSV F and G proteins in human cells and purify these proteins using Ni Sepharose affinity chromatography.

  4. Application of morphological and physiological parameters representative of a Brazilian population sample in the respiratory tract model

    International Nuclear Information System (INIS)

    Dos Reis, A. A.; Cardoso, J. C. S.; Lourenco, M. C.

    2007-01-01

    The human respiratory tract model (HRTM) adopted by ICRP in its Publication 66 accounts for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. These characteristics are important to determine the fractional deposition. It is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends, for a reliable evaluation of the regional deposition, the use of parameters from a local population wherever such information is available. The main purpose of this study is to verify the influence of using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of the ICRP Publication 66 model. (authors)

  5. The respiratory tract deposition model proposed by the ICRP Task Group

    International Nuclear Information System (INIS)

    James, A.C.; Briant, J.K.; Stahlhofen, W.; Rudolf, G.; Gehr, P.

    1990-11-01

    The Task Group has developed a new model of the deposition of inhaled aerosols in each anatomical region of the respiratory tract. The model is used to evaluate the fraction of airborne activity that is deposited in respiratory regions having distinct retention characteristics and clearance pathways: the anterior nares, the extrathoracic airways of the naso- and oropharynx and larynx, the bronchi, the bronchioles, and the alveolated airways of the lung. Drawn from experimental data on total and regional deposition in human subjects, the model is based on extrapolation of these data by means of a detailed theoretical model of aerosol transport and deposition within the lung. The Task Group model applies to all practical conditions, and for aerosol particles and vapors from atomic size up to very coarse aerosols with an activity median aerodynamic diameter of 100 μm. The model is designed to predict regional deposition in different subjects, including adults of either sex, children of various ages, and infants, and also to account for anatomical differences among Caucasian and non-Caucasian subjects. The Task Group model represents aerosol inhalability and regional deposition in different subjects by algebraic expressions of aerosol size, breathing rates, standard lung volumes, and scaling factors for airway dimensions. 35 refs., 13 figs., 2 tabs

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

    Science.gov (United States)

    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.

  7. Tamoxifen does not inhibit the swell activated chloride channel in human neutrophils during the respiratory burst.

    Science.gov (United States)

    Ahluwalia, Jatinder

    2008-10-31

    Effective functioning of neutrophils relies upon electron translocation through the NADPH oxidase (NOX). The electron current generated (I(e)) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential in activated human neutrophils. Swelling activated chloride channels have been demonstrated in part to counteract the depolarisation generated by the NADPH oxidase I(e). In the present study, the effects of inhibitors of swell activated chloride channels on ROS production and on the swelling activated chloride conductance was investigated in activated human neutrophils. Tamoxifen (10 microM), a specific inhibitor for swell activated chloride channels in neutrophils, completely inhibited both the PMA and FMLP stimulated respiratory burst. This inhibition of the neutrophil respiratory burst was not due to the blocking effect of tamoxifen on the swelling activated chloride conductance in these cells. These results demonstrate that a tamoxifen insensitive swell activated chloride channel has important significance during the neutrophil respiratory burst.

  8. Binding of Haemophilus influenzae to purified mucins from the human respiratory tract

    NARCIS (Netherlands)

    Davies, J.; Carlstedt, I.; Nilsson, A. K.; Håkansson, A.; Sabharwal, H.; van Alphen, L.; van Ham, M.; Svanborg, C.

    1995-01-01

    Mucins are high-molecular-weight glycoproteins and major constituents of the mucus layer which covers the airway surface. We have studied the interactions between bacteria, mucins, and epithelial cells from the human respiratory tract. Nontypeable strains of Haemophilus influenzae were found to bind

  9. Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung

    NARCIS (Netherlands)

    de Bree, Godelieve J.; van Leeuwen, Ester M. M.; Out, Theo A.; Jansen, Henk M.; Jonkers, René E.; van Lier, René A. W.

    2005-01-01

    The lungs are frequently challenged by viruses, and resident CD8(+) T cells likely contribute to the surveillance of these pathogens. To obtain insight into local T cell immunity to respiratory viruses in humans, we determined the specificity, phenotype, and function of lung-residing CD8(+) T cells

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

    Science.gov (United States)

    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

  11. Models of human operators

    International Nuclear Information System (INIS)

    Knee, H.E.; Schryver, J.C.

    1991-01-01

    Models of human behavior and cognition (HB and C) are necessary for understanding the total response of complex systems. Many such models have come available over the past thirty years for various applications. Unfortunately, many potential model users remain skeptical about their practicality, acceptability, and usefulness. Such hesitancy stems in part to disbelief in the ability to model complex cognitive processes, and a belief that relevant human behavior can be adequately accounted for through the use of commonsense heuristics. This paper will highlight several models of HB and C and identify existing and potential applications in attempt to dispel such notions. (author)

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

    Science.gov (United States)

    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.

  13. Reflex influence of carotid baroreceptor inactivation on respiratory resistance in humans

    Directory of Open Access Journals (Sweden)

    Klawe JJ

    2009-12-01

    Full Text Available Abstract Our previous study demonstrated that selective carotid baroreceptors activation decreases airway resistance. The aim of the present study was to evaluate the effect of carotid baroreceptor inactivation on the reflex change of respiratory resistance. Twenty healthy men aged between 20 and 25 were included in the study. Selective inactivation of carotid baroreceptors was induced by generating a positive pressure of 40 mmHg for 5 s in two capsules placed bilaterally on the neck over the bifurcation of the carotid arteries. The oscillatory method (Siregnost FD5, Siemens was used to measure continuously respiratory resistance. Inactivation of carotid baroreceptors produced a short increase in respiratory resistance by 0.39 ± 0.01(SE mbar/l/s, i.e., 21.7% above the resting level. We conclude that in humans, carotid baroreceptors might have a background contribution to bronchodilator tone. This observation seems to be important for clinical situations of impairment of baroreflex function.

  14. Digital anthropomorphic phantoms of non-rigid human respiratory and voluntary body motion for investigating motion correction in emission imaging

    International Nuclear Information System (INIS)

    Könik, Arda; Johnson, Karen L; Dasari, Paul; Pretorius, P H; Dey, Joyoni; King, Michael A; Connolly, Caitlin M; Segars, Paul W; Lindsay, Clifford

    2014-01-01

    The development of methods for correcting patient motion in emission tomography has been receiving increased attention. Often the performance of these methods is evaluated through simulations using digital anthropomorphic phantoms, such as the commonly used extended cardiac torso (XCAT) phantom, which models both respiratory and cardiac motion based on human studies. However, non-rigid body motion, which is frequently seen in clinical studies, is not present in the standard XCAT phantom. In addition, respiratory motion in the standard phantom is limited to a single generic trend. In this work, to obtain a more realistic representation of motion, we developed a series of individual-specific XCAT phantoms, modeling non-rigid respiratory and non-rigid body motions derived from the magnetic resonance imaging (MRI) acquisitions of volunteers. Acquisitions were performed in the sagittal orientation using the Navigator methodology. Baseline (no motion) acquisitions at end-expiration were obtained at the beginning of each imaging session for each volunteer. For the body motion studies, MRI was again acquired only at end-expiration for five body motion poses (shoulder stretch, shoulder twist, lateral bend, side roll, and axial slide). For the respiratory motion studies, an MRI was acquired during free/regular breathing. The magnetic resonance slices were then retrospectively sorted into 14 amplitude-binned respiratory states, end-expiration, end-inspiration, six intermediary states during inspiration, and six during expiration using the recorded Navigator signal. XCAT phantoms were then generated based on these MRI data by interactive alignment of the organ contours of the XCAT with the MRI slices using a graphical user interface. Thus far we have created five body motion and five respiratory motion XCAT phantoms from the MRI acquisitions of six healthy volunteers (three males and three females). Non-rigid motion exhibited by the volunteers was reflected in both respiratory

  15. Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset.

    Science.gov (United States)

    Chen, Zhe; Bao, Linlin; Chen, Cong; Zou, Tingting; Xue, Ying; Li, Fengdi; Lv, Qi; Gu, Songzhi; Gao, Xiaopan; Cui, Sheng; Wang, Jianmin; Qin, Chuan; Jin, Qi

    2017-06-15

    Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings. © Crown copyright 2017.

  16. Mucosal inflammation at the respiratory interface: a zebrafish model

    OpenAIRE

    Progatzky, Fr?nze; Cook, H. Terence; Lamb, Jonathan R.; Bugeon, Laurence; Dallman, Margaret J.

    2015-01-01

    Inflammatory diseases of the respiratory system such as asthma and chronic obstructive pulmonary disease are increasing globally and remain poorly understood conditions. Although attention has long focused on the activation of type 1 and type 2 helper T cells of the adaptive immune system in these diseases, it is becoming increasingly apparent that there is also a need to understand the contributions and interactions between innate immune cells and the epithelial lining of the respiratory sys...

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

    Science.gov (United States)

    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.

  18. Characterizing and Diminishing Autofluorescence in Formalin-fixed Paraffin-embedded Human Respiratory Tissue

    Science.gov (United States)

    Davis, A. Sally; Richter, Anke; Becker, Steven; Moyer, Jenna E.; Sandouk, Aline; Skinner, Jeff

    2014-01-01

    Tissue autofluorescence frequently hampers visualization of immunofluorescent markers in formalin-fixed paraffin-embedded respiratory tissues. We assessed nine treatments reported to have efficacy in reducing autofluorescence in other tissue types. The three most efficacious were Eriochrome black T, Sudan black B and sodium borohydride, as measured using white light laser confocal Λ2 (multi-lambda) analysis. We also assessed the impact of steam antigen retrieval and serum application on human tracheal tissue autofluorescence. Functionally fitting this Λ2 data to 2-dimensional Gaussian surfaces revealed that steam antigen retrieval and serum application contribute minimally to autofluorescence and that the three treatments are disparately efficacious. Together, these studies provide a set of guidelines for diminishing autofluorescence in formalin-fixed paraffin-embedded human respiratory tissue. Additionally, these characterization techniques are transferable to similar questions in other tissue types, as demonstrated on frozen human liver tissue and paraffin-embedded mouse lung tissue fixed in different fixatives. PMID:24722432

  19. Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

    Directory of Open Access Journals (Sweden)

    Tzeng-Jih Lin

    2013-12-01

    Full Text Available Human respiratory syncytial virus (HRSV infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata is a common ingredient of Ge-Gen-Tang (Kakkon-to and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to, which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2 and lower (A549 respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001 against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001 by inhibiting viral attachment (p < 0.0001 and penetration (p < 0.0001. However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

  20. Codetection of Respiratory Syncytial Virus in Habituated Wild Western Lowland Gorillas and Humans During a Respiratory Disease Outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:60077344 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: EE - Microbiology, Virology Impact factor: 2.252, year: 2016

  1. Codetection of respiratory syncytial virus in habituated wild western lowland gorillas and humans during a respiratory disease outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:68081766 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: GJ - Animal Vermins ; Disease s, Veterinary Medicine Impact factor: 2.252, year: 2016

  2. Seasonal behavior of radon decay products in indoor air and resulting radiation dose to human respiratory tract

    Directory of Open Access Journals (Sweden)

    A.M.A. Mostafa

    2015-01-01

    Full Text Available Most of radiation hazard of indoor radon is largely due to the radon progenies, which are inhaled and deposited in the human respiratory tract. It is essential to evaluate aerodynamic characteristics of the radon progenies, which are either attached or unattached to aerosol particles, because the dose is strongly dependent on the location of deposition in respiratory tract and hence on the aerodynamic characteristics of the aerosol particles. This paper presents the seasonal behavior of radon decay products in indoor air under domestic conditions at Nagoya University, Japan. A low pressure cascade impactor as an instrument for classifying aerosol sizes and imaging plate as a radiation detector have been employed to characterize the activity size distribution of short-lived radon decay products. In parallel, radon and its progenies concentrations were measured. Taking into account the progeny characteristics, the inhalation dose in the different seasons was also estimated based on a lung dose model with the structure that is related to the ICRP66 respiratory tract model. The result evident that, the highest dose 0.22 mSvy−1 was observed during the winter where the highest value of equilibrium equivalent concentration of radon (EEC and lowest value of the activity median aerodynamic diameter (AMAD were found in this season; whereas, the dose in spring appeared to be lowest 0.02 mSvy−1.

  3. Distance to human populations influences epidemiology of respiratory disease in desert tortoises

    Science.gov (United States)

    Berry, Kristin H.; Ashley A. Coble (formerly Emerson), no longer USGS; Yee, Julie L.; Mack, Jeremy S.; Perry, William M.; Anderson, Kemp M.; Brown, Mary B.

    2014-01-01

    We explored variables likely to affect health of Agassiz's desert tortoises (Gopherus agassizii) in a 1,183-km2 study area in the central Mojave Desert of California between 2005 and 2008. We evaluated 1,004 tortoises for prevalence and spatial distribution of 2 pathogens, Mycoplasma agassizii and M. testudineum, that cause upper respiratory tract disease. We defined tortoises as test-positive if they were positive by culture and/or DNA identification or positive or suspect for specific antibody for either of the two pathogens. We used covariates of habitat (vegetation, elevation, slope, and aspect), tortoise size and sex, distance from another test-positive tortoise, and anthropogenic variables (distances to roads, agricultural areas, playas, urban areas, and centroids of human-populated census blocks). We used both logistic regression models and regression trees to evaluate the 2 species of Mycoplasma separately. The prevalence of test-positive tortoises was low: 1.49% (15/1,004) for M. agassizii and 2.89% (29/1,004) for M. testudineum. The spatial distributions of test-positive tortoises for the 2 Mycoplasma species showed little overlap; only 2 tortoises were test-positive for both diseases. However, the spatial distributions did not differ statistically between the 2 species. We consistently found higher prevalence of test-positive tortoises with shorter distances to centroids of human-populated census blocks. The relationship between distance to human-populated census blocks and tortoises that are test-positive for M. agassizii and potentially M. testudineum may be related to release or escape of captive tortoises because the prevalence of M. agassizii in captive tortoises is high. Our findings have application to other species of chelonians where both domestic captive and wild populations exist. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  4. Human metapneumovirus found in clinical materials of children with respiratory tract diseases

    Directory of Open Access Journals (Sweden)

    Katarina Logar

    2006-10-01

    Full Text Available Background: Human metapneumovirus (hMPV was first recognized in the Netherlands in 2001. Since then, it has been documented all over the world as a cause of human respiratory infections in all age groups. The objective of this study was to introduce and optimize an assay for detecting hMPV in clinical material of our patients. To date, there has not been a report that describes the detection of this virus in Slovenia.Methods: A total of 58 specimens, randomly collected during 2003/2004 from the patients ≤ 19 years old with respiratory disease and 20 specimens collected in 1997 were tested for hMPV. Extraction of RNA from frozen specimens and subsequent single-step reverse transcription-polymerase chain reaction (RT-PCR were performed. Human metapneumovirus amplicons were determined by electrophoresis in a 2 % (w/v agarose gel.Results: Human metapneumovirus was detected in 13/58 (22 % specimens; 10/40 (25 % specimens were from the upper and 3/18 (17 % from the lower respiratory tract. The mean age of infected patients was 3.2 ± 2.2 years. Out of 13 of the hMPV-positive specimens, 9 were positive also for another respiratory virus. Two of 20 (10 % archival specimens were hMPV-positive.Conclusions: This study is the first report about hMPV in Slovenia. Human metapneumovirus was detected as the second most frequent virus after RSV in children < 3 years of age. The virus was not found in the specimens from the children younger than 2 months. Based on the hMPV-positive results in archival clinical material, it is suggested that hMPV had circulated in Slovenia before the time it was discovered.

  5. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  6. The influence of a fentanyl and dexmedetomidine combination on external respiratory functions in acute hemorrhage model

    Directory of Open Access Journals (Sweden)

    Nikolay G. Vengerovich

    2017-01-01

    Full Text Available Background. The synthetic opioid analgesic fentanyl is widely used for prophylaxis and therapy of traumatic shock associated with massive bleeding. Its side effects – skeletal muscle rigidity and respiratory center depression – are especially pronounced with repeated administration. It is rational to apply fentanyl in diminished doses in combination with non-opioid analgesics in order to reduce respiratory disturbances risk.Aim. The aim of the work is to justify the influence of opioid analgesic fentanyl and α2 -adrenomimetic dexmedetomidine combination on external respiratory functions in acute hemorrhage model.Materials and methods. Acute loss of 35–40% of circulating blood volume was modeled in experiments on 75 white mongrel male rats. The external respiratory functions (respiratory rate, respiratory volume, breath volume per minute were estimated in animals of 5 groups: 1 – rats without analgesic help (controls; 2–3 – rats receiving a single fentanyl intramuscular injection (ED99 98,96 mcg/kg or fentanyl together with dexme detomidine (ED99 of combination 67,94 mcg/kg 15 min after acute blood loss; 4–5 – rats receiving the same drugs 15 min, 30, 45 and 60 min later.Results. In experimental acute loss of 35–40% of circulating blood volume, 15 min later a secondary acute respiratory failure developed with a drop of respiratory rate, respiratory volume and volume of breath per minute by 30%, 21 and 47% (p < 0,05. The external respiratory functions recoverеd after 4 h mainly due to the increase of respiratory volume. A single intramuscular injection of fentanyl caused respiratory depression 15 min after experimental blood loss which resulted in the decrease of breath volume per minute to 30–61% (p < 0,05 for 90 min. Four intramuscular injections of fentanyl 15 min, 30, 45 and 60 min after hemorrhage caused a severe respiratory dysfunction, accompanied by apnea periods and Biot’s respiration. Respiratory rate was reduced

  7. Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells.

    Science.gov (United States)

    Hung, Sandy S C; Van Bergen, Nicole J; Jackson, Stacey; Liang, Helena; Mackey, David A; Hernández, Damián; Lim, Shiang Y; Hewitt, Alex W; Trounce, Ian; Pébay, Alice; Wong, Raymond C B

    2016-05-01

    Reprogramming of somatic cells into a pluripotent state is known to be accompanied by extensive restructuring of mitochondria and switch in metabolic requirements. Here we utilized Leber's hereditary optic neuropathy (LHON) as a mitochondrial disease model to study the effects of homoplasmic mtDNA mutations and subsequent oxidative phosphorylation (OXPHOS) defects in reprogramming. We obtained fibroblasts from a total of 6 LHON patients and control subjects, and showed a significant defect in complex I respiration in LHON fibroblasts by high-resolution respiratory analysis. Using episomal vector reprogramming, our results indicated that human induced pluripotent stem cell (hiPSC) generation is feasible in LHON fibroblasts. In particular, LHON-specific OXPHOS defects in fibroblasts only caused a mild reduction and did not significantly affect reprogramming efficiency, suggesting that hiPSC reprogramming can tolerate a certain degree of OXPHOS defects. Our results highlighted the induction of genes involved in mitochondrial biogenesis (TFAM, NRF1), mitochondrial fusion (MFN1, MFN2) and glycine production (GCAT) during reprogramming. However, LHON-associated OXPHOS defects did not alter the kinetics or expression levels of these genes during reprogramming. Together, our study provides new insights into the effects of mtDNA mutation and OXPHOS defects in reprogramming and genes associated with various aspects of mitochondrial biology.

  8. Ameliorating Effect of Dietary Xylitol on Human Respiratory Syncytial Virus (hRSV) Infection.

    Science.gov (United States)

    Xu, Mei Ling; Wi, Ga Ram; Kim, Hyoung Jin; Kim, Hong-Jin

    2016-01-01

    Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in infants. The lack of proper prophylactics and therapeutics for controlling hRSV infection has been of great concern worldwide. Xylitol is a well-known sugar substitute and its effect against bacteria in the oral cavity is well known. However, little is known of its effect on viral infections. In this study, the effect of dietary xylitol on hRSV infection was investigated in a mouse model for the first time. Mice received xylitol for 14 d prior to virus challenge and for a further 3 d post challenge. Significantly larger reductions in lung virus titers were observed in the mice receiving xylitol than in the controls receiving phosphate-buffered saline (PBS). In addition, fewer CD3(+) and CD3(+)CD8(+) lymphocytes, whose numbers reflect inflammatory status, were recruited in the mice receiving xylitol. These results indicate that dietary xylitol can ameliorate hRSV infections and reduce inflammation-associated immune responses to hRSV infection.

  9. Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative human physiology.

    Science.gov (United States)

    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.

  10. A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition

    OpenAIRE

    Kumar, Abhinav; Terakosolphan, Wachirun; Hassoun, Mireille; Vandera, Kalliopi-Kelli; Novicky, Astrid; Harvey, Richard; Royall, Paul G.; Bicer, Elif Melis; Eriksson, Jonny; Edwards, Katarina; Valkenborg, Dirk; Nelissen, Inge; Hassall, Dave; Mudway, Ian S.; Forbes, Ben

    2017-01-01

    Purpose: To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays. Methods: The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveola...

  11. Evidence for activation of a respiratory burst in the interaction of human neutrophils with Mycobacterium tuberculosis.

    OpenAIRE

    May, M E; Spagnuolo, P J

    1987-01-01

    We examined the capacity of human neutrophils to develop a respiratory burst, as monitored by superoxide release, in response to interaction with Mycobacterium tuberculosis. Serum-opsonized, heat-killed mycobacteria induced significant release of superoxide from neutrophils after 30 min of exposure, with a maximum release of 34 +/- 1.7 nmol/30 min per 5 X 10(6) neutrophils occurring with a mycobacterium/neutrophil ratio of 40:1. Similar levels of superoxide release were induced by live mycoba...

  12. Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

    Science.gov (United States)

    Pancham, Krishna; Sami, Iman; Perez, Geovanny F; Huseni, Shehlanoor; Kurdi, Bassem; Rose, Mary C; Rodriguez-Martinez, Carlos E; Nino, Gustavo

    2016-02-01

    Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity. We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (≤5 years) with and without history of severe prematurity (prematurity. Preschool children with a history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity, and history of asthma. Our study suggests that HMPV infection causes significant disease burden among preschool children with a history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations. Copyright © 2016. Published by Elsevier B.V.

  13. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...... for the induced headache and migraine. Perspectives are discussed....

  14. A Model of Locomotor-Respiratory Coupling in Quadrupeds

    Science.gov (United States)

    Giuliodori,, Mauricio J.; Lujan, Heidi L.; Briggs, Whitney S.; DiCarlo, Stephen E.

    2009-01-01

    Locomotion and respiration are not independent phenomena in running mammals because locomotion and respiration both rely on cyclic movements of the ribs, sternum, and associated musculature. Thus, constraints are imposed on locomotor and respiratory function by virtue of their linkage. Specifically, locomotion imposes mechanical constraints on…

  15. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

    Directory of Open Access Journals (Sweden)

    Eduardo Gómez-Gómez

    Full Text Available Carnitine palmitoyltransferase IB (CPT1B and adrenoceptor beta-3 (ADRB3 are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate and fat oxidation (through the non-protein respiratory quotient. These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.

  16. Novel avian-origin human influenza A(H7N9) can be transmitted between ferrets via respiratory droplets.

    Science.gov (United States)

    Xu, Lili; Bao, Linlin; Deng, Wei; Dong, Libo; Zhu, Hua; Chen, Ting; Lv, Qi; Li, Fengdi; Yuan, Jing; Xiang, Zhiguang; Gao, Kai; Xu, Yanfeng; Huang, Lan; Li, Yanhong; Liu, Jiangning; Yao, Yanfeng; Yu, Pin; Li, Xiyan; Huang, Weijuan; Zhao, Xiang; Lan, Yu; Guo, Junfeng; Yong, Weidong; Wei, Qiang; Chen, Honglin; Zhang, Lianfeng; Qin, Chuan

    2014-02-15

    The outbreak of human infections caused by novel avian-origin influenza A(H7N9) in China since March 2013 underscores the need to better understand the pathogenicity and transmissibility of these viruses in mammals. In a ferret model, the pathogenicity of influenza A(H7N9) was found to be less than that of an influenza A(H5N1) strain but comparable to that of 2009 pandemic influenza A(H1N1), based on the clinical signs, mortality, virus dissemination, and results of histopathologic analyses. Influenza A(H7N9) could replicate in the upper and lower respiratory tract, the heart, the liver, and the olfactory bulb. It is worth noting that influenza A(H7N9) exhibited a low level of transmission between ferrets via respiratory droplets. There were 4 mutations in the virus isolated from the contact ferret: D678Y in the gene encoding PB2, R157K in the gene encoding hemagglutinin (H3 numbering), I109T in the gene encoding nucleoprotein, and T10I in the gene encoding neuraminidase. These data emphasized that avian-origin influenza A(H7N9) can be transmitted between mammals, highlighting its potential for human-to-human transmissibility.

  17. Architecture of Human Mitochondrial Respiratory Megacomplex I2III2IV2.

    Science.gov (United States)

    Guo, Runyu; Zong, Shuai; Wu, Meng; Gu, Jinke; Yang, Maojun

    2017-09-07

    The respiratory megacomplex represents the highest-order assembly of respiratory chain complexes, and it allows mitochondria to respond to energy-requiring conditions. To understand its architecture, we examined the human respiratory chain megacomplex-I 2 III 2 IV 2 (MCI 2 III 2 IV 2 ) with 140 subunits and a subset of associated cofactors using cryo-electron microscopy. The MCI 2 III 2 IV 2 forms a circular structure with the dimeric CIII located in the center, where it is surrounded by two copies each of CI and CIV. Two cytochrome c (Cyt.c) molecules are positioned to accept electrons on the surface of the c 1 state CIII dimer. Analyses indicate that CII could insert into the gaps between CI and CIV to form a closed ring, which we termed the electron transport chain supercomplex. The structure not only reveals the precise assignment of individual subunits of human CI and CIII, but also enables future in-depth analysis of the electron transport chain as a whole. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Antiviral effect of cimicifugin from Cimicifuga foetida against human respiratory syncytial virus.

    Science.gov (United States)

    Wang, Kuo-Chih; Chang, Jung-San; Lin, Liang-Tzung; Chiang, Lien-Chai; Lin, Chun-Ching

    2012-01-01

    Human respiratory syncytial virus (RSV) causes serious infection of the lower respiratory tract in children and an effective antiviral therapy against the viral pathogen remains unavailable. We previously demonstrated that the oriental medicinal plant, Cimicifuga foetida L. (C. foetida), possessed inhibitory activity against RSV. Since cimicifugin is a major constituent of C. foetida, we sought to examine in this study its anti-RSV effect on both the human upper (HEp-2) and lower (A549) respiratory tract cell lines. Results revealed that cimicifugin dose-dependently inhibited RSV-induced plaque formation in both HEp-2 and A549 cells (p < 0.0001), with a superior effect in the latter cell type (p < 0.0001). The antiviral activity of cimicifugin was time-dependent (p < 0.0001) and was most effective when cells were treated with the compound before viral inoculation. Additional experiments demonstrated that cimicifugin could inhibit viral attachment (p < 0.0001) and viral internalization (p < 0.0001). Furthermore, the drug could potentiate heparin's effect against attachment of RSV, particularly in A549 cells. Enzyme-linked immunosorbent assay (ELISA) analysis of antiviral cytokines induction revealed that cimicifugin could also stimulate epithelial cells to secrete IFN-β to counteract viral infection. Taken together, these results indicate that cimicifugin is an efficient antiviral agent against RSV infection. We suggest that cimicifugin might be useful for the management of RSV pathogenesis.

  19. Cimicifuga foetida L. inhibited human respiratory syncytial virus in HEp-2 and A549 cell lines.

    Science.gov (United States)

    Wang, Kuo Chih; Chang, Jung San; Chiang, Lien Chai; Lin, Chun Ching

    2012-01-01

    Human respiratory syncytial virus (HRSV) causes serious pediatric infection of the lower respiratory tract without effective therapeutic modality. Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) has been proven to be effective at inhibiting HRSV-induced plaque formation, and Cimicifuga foetida is the major constituent of SMGGT. We tested the hypothesis that C. foetida effectively inhibited the cytopathic effects of HRSV by a plaque reduction assay in both human upper (HEp2) and lower (A549) respiratory tract cell lines. Its ability to stimulate anti-viral cytokines was evaluated by an enzyme-linked immunosorbent assay (ELISA). C. foetida dose-dependently inhibited HRSV-induced plaque formation (p < 0.0001) before and after viral inoculation, especially in A549 cells (p < 0.0001). C. foetida dose-dependently inhibited viral attachment (p < 0.0001) and could increase heparins effect on viral attachment. In addition, C. foetida time-dependently and dose-dependently (p < 0.0001) inhibited HRSV internalization. C. foetida could stimulate epithelial cells to secrete IFN-β to counteract viral infection. However, C. foetida did not stimulate TNF-α secretion. Therefore, C. foetida could be useful in managing HRSV infection. This is the first evidence to support that C. foetida possesses antiviral activity.

  20. Time-varying respiratory system elastance: a physiological model for patients who are spontaneously breathing.

    Science.gov (United States)

    Chiew, Yeong Shiong; Pretty, Christopher; Docherty, Paul D; Lambermont, Bernard; Shaw, Geoffrey M; Desaive, Thomas; Chase, J Geoffrey

    2015-01-01

    Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no spontaneously breathing efforts. This research presents a time-varying elastance (E(drs)) model that can be used in spontaneously breathing patients to determine their respiratory mechanics. A time-varying respiratory elastance model is developed with a negative elastic component (E(demand)), to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS) and Neurally Adjusted Ventilatory Assist (NAVA) are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. E(drs) of every breathing cycle for each patient at different ventilation modes are presented for comparison. At the start of every breathing cycle initiated by patient, E(drs) is 25 cmH2Os/l and thus can be used as an acute respiratory distress syndrome (ARDS) severity indicator. The E(drs) model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes.

  1. Time-varying respiratory system elastance: a physiological model for patients who are spontaneously breathing.

    Directory of Open Access Journals (Sweden)

    Yeong Shiong Chiew

    Full Text Available BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV, but the applications are limited to fully sedated MV patients who have little or no spontaneously breathing efforts. This research presents a time-varying elastance (E(drs model that can be used in spontaneously breathing patients to determine their respiratory mechanics. METHODS: A time-varying respiratory elastance model is developed with a negative elastic component (E(demand, to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS and Neurally Adjusted Ventilatory Assist (NAVA are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. E(drs of every breathing cycle for each patient at different ventilation modes are presented for comparison. RESULTS: At the start of every breathing cycle initiated by patient, E(drs is 25 cmH2Os/l and thus can be used as an acute respiratory distress syndrome (ARDS severity indicator. CONCLUSION: The E(drs model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes.

  2. Effects of pacifier and taste on swallowing, esophageal motility, transit, and respiratory rhythm in human neonates.

    Science.gov (United States)

    Shubert, T R; Sitaram, S; Jadcherla, S R

    2016-04-01

    Pacifier use is widely prevalent globally despite hygienic concerns and uncertain mechanistic effects on swallowing or airway safety. The effects of pacifier and taste interventions on pharyngo-esophageal motility, bolus transit, and respiratory rhythms were investigated by determining the upper esophageal sphincter (UES), esophageal body, esophagogastric junction (EGJ) motor patterns and deglutition apnea, respiratory rhythm disturbances, and esophageal bolus clearance. Fifteen infants (six males; median gestation 31 weeks and birth weight 1.4 kg) underwent high-resolution impedance manometry at 43 (41-44) weeks postmenstrual age. Manometric, respiratory, and impedance characteristics of spontaneous swallows, pacifier-associated dry swallowing and taste (pacifier dipped in 3% sucrose)-associated swallowing were analyzed. Linear mixed and generalized estimating equation models were used. Data are presented as mean ± SEM, %, or median (IQR). Pharyngo-esophageal motility, respiratory, and impedance characteristics of 209 swallows were analyzed (85 spontaneous swallows, 63 pacifier- swallows, 61 taste- swallows). Basal UES and EGJ pressures decreased upon pacifier (p pacifier or taste interventions decreases UES and EGJ basal pressure, but has no effects on pharyngo-esophageal motility, airway interactions, or esophageal bolus transit. A decrease in central parasympathetic-cholinergic excitatory drive is likely responsible for the basal effects. © 2016 John Wiley & Sons Ltd.

  3. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection.

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    Trevenan Walther

    2013-03-01

    Full Text Available The first step in influenza infection of the human respiratory tract is binding of the virus to sialic (Sia acid terminated receptors. The binding of different strains of virus for the receptor is determined by the α linkage of the sialic acid to galactose and the adjacent glycan structure. In this study the N- and O-glycan composition of the human lung, bronchus and nasopharynx was characterized by mass spectrometry. Analysis showed that there was a wide spectrum of both Sia α2-3 and α2-6 glycans in the lung and bronchus. This glycan structural data was then utilized in combination with binding data from 4 of the published glycan arrays to assess whether these current glycan arrays were able to predict replication of human, avian and swine viruses in human ex vivo respiratory tract tissues. The most comprehensive array from the Consortium for Functional Glycomics contained the greatest diversity of sialylated glycans, but was not predictive of productive replication in the bronchus and lung. Our findings indicate that more comprehensive but focused arrays need to be developed to investigate influenza virus binding in an assessment of newly emerging influenza viruses.

  4. Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

    Directory of Open Access Journals (Sweden)

    Guangyu Zhao

    Full Text Available The Middle East Respiratory Syndrome Coronavirus (MERS-CoV causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4, the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.

  5. Central nervous system alterations caused by infection with the human respiratory syncytial virus.

    Science.gov (United States)

    Bohmwald, Karen; Espinoza, Janyra A; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2014-11-01

    Worldwide, the human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization because of acute respiratory tract infections, including severe bronchiolitis and pneumonia. Despite intense research, to date there is neither vaccine nor treatment available to control hRSV disease burden globally. After infection, an incubation period of 3-5 days is usually followed by symptoms, such as cough and low-grade fever. However, hRSV infection can also produce a larger variety of symptoms, some of which relate to the individual's age at infection. Indeed, infants can display severe symptoms, such as dyspnea and chest wall retractions. Upon examination, crackles and wheezes are also common features that suggest infection by hRSV. Additionally, infection in infants younger than 1 year is associated with several non-specific symptoms, such as failure to thrive, periodic breathing or apnea, and feeding difficulties that usually require hospitalization. Recently, neurological symptoms have also been associated with hRSV respiratory infection and include seizures, central apnea, lethargy, feeding or swallowing difficulties, abnormalities in muscle tone, strabismus, abnormalities in the CSF, and encephalopathy. Here, we discuss recent findings linking the neurological, extrapulmonary effects of hRSV with infection and functional impairment of the CNS. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt

    Science.gov (United States)

    Embarek Mohamed, Mona S.; Jacobsen, Sonja; Thabit, Amany G.; Badary, Mohamed S.; Brune, Wolfram; Schweiger, Brunhilde; Osmann, Ahmed H.

    2014-01-01

    Introduction. Since 2001, when Human metapneumovirus (HMPV) was isolated in the Netherlands, the virus has been detected in several continents. Although reports have confirmed the prevalence of HMPV worldwide, data from Egypt remain limited. HMPV plays an important role in respiratory tract infections in individuals of all ages particularly in children. This study was aimed at estimating the prevalence of HMPV in patients with community-acquired lower respiratory infection in Upper Egypt and characterizing the circulating Egyptian HMPV strains for the first time. Materials and Methods. From 2005 to 2008, respiratory samples from 520 patients were analyzed for the presence of HMPV by real-time RT-PCR. Molecular and phylogenetic analyses were performed on partial fusion gene sequences of HMPV-positive patients. Results. HMPV-positive patients were detected in 2007-2008. The overall infection rate was 4%, while 57% of the patients were children. Sequence analysis demonstrated circulation of subgroup B viruses with predominance of lineage B2. Nucleotide sequence identity within lineage B1 was 98.8%–99.7% and higher than that in lineage B2 (94.3%–100%). Three new amino acid substitutions (T223N, R229K, and D280N) of lineage B2 were observed. Conclusion. HMPV is a major viral pathogen in the Egyptian population especially in children. During 2007-2008, predominantly HMPV B2 circulated in Upper Egypt. PMID:24669221

  7. Human Pharyngeal Microbiome May Play A Protective Role in Respiratory Tract Infections

    Directory of Open Access Journals (Sweden)

    Zhancheng Gao

    2014-06-01

    Full Text Available The human pharyngeal microbiome, which resides at the juncture of digestive and respiratory tracts, may have an active role in the prevention of respiratory tract infections, similar to the actions of the intestinal microbiome against enteric infections. Recent studies have demonstrated that the pharyngeal microbiome comprises an abundance of bacterial species that interacts with the local epithelial and immune cells, and together, they form a unique micro-ecological system. Most of the microbial species in microbiomes are obligate symbionts constantly adapting to their unique surroundings. Indigenous commensal species are capable of both maintaining dominance and evoking host immune responses to eliminate invading species. Temporary damage to the pharyngeal microbiome due to the impaired local epithelia is also considered an important predisposing risk factor for infections. Therefore, reinforcement of microbiome homeostasis to prevent invasion of infection-prone species would provide a novel treatment strategy in addition to antibiotic treatment and vaccination. Hence continued research efforts on evaluating probiotic treatment and developing appropriate procedures are necessary to both prevent and treat respiratory infections.

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

    Science.gov (United States)

    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.

  9. Recombinant subgroup B human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats.

    Science.gov (United States)

    Lemon, Ken; Nguyen, D Tien; Ludlow, Martin; Rennick, Linda J; Yüksel, Selma; van Amerongen, Geert; McQuaid, Stephen; Rima, Bert K; de Swart, Rik L; Duprex, W Paul

    2015-03-01

    Human respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro and in vivo models of HRSV focus almost exclusively on subgroup A viruses. Here, a recombinant (r) subgroup B virus (rHRSV(B05)) was generated based on a consensus genome sequence obtained directly from an unpassaged clinical specimen from a hospitalized infant. An additional transcription unit containing the gene encoding enhanced green fluorescent protein (EGFP) was introduced between the phosphoprotein and matrix genes (position 5) of the genome to generate rHRSV(B05)EGFP(5). The recombinant viruses replicated efficiently in both HEp-2 cells and in well-differentiated normal human bronchial cells grown at air-liquid interface. Intranasal infection of cotton rats (Sigmodon hispidus) resulted in high numbers of EGFP(+) cells in epithelia of the nasal septum and conchae. When administered in a relatively large inoculum volume, the virus also replicated efficiently in bronchiolar epithelial cells and spread extensively in both the upper and lower respiratory tracts. Virus replication was not observed in ciliated epithelial cells of the trachea. This is the first virulent rHRSV strain with the genetic composition of a currently circulating wild-type virus. In vivo tracking of infected cells by means of EGFP fluorescence in the absence of cytopathic changes increases the sensitivity of virus detection in HRSV pathogenesis studies. Virology as a discipline has depended on monitoring cytopathic effects following virus culture in vitro. However, wild-type viruses isolated from patients often do not cause significant changes to infected cells, necessitating blind passage. This can lead to genetic and phenotypic changes and the generation of high-titer, laboratory-adapted viruses with

  10. Molecular epidemiology of human respiratory syncytial virus over three consecutive seasons in Latvia.

    Science.gov (United States)

    Balmaks, Reinis; Ribakova, Irina; Gardovska, Dace; Kazaks, Andris

    2014-11-01

    Lower respiratory tract infections caused by the human respiratory syncytial virus (HRSV) represent an immense burden of the disease, especially in young children. This study aimed to investigate the evolutionary history of HRSV strains isolated in the Children's Clinical University Hospital (Riga, Latvia) over three consecutive HRSV seasons. Of 207 samples from children hospitalized with lower respiratory tract infections, 88 (42.5%) tested positive for HRSV by RT-PCR. The seasonal activity started and peaked later than the average for the Northern hemisphere. Patients with HRSV lower respiratory tract infection were significantly younger than patients not infected with HRSV. HRSV-A viruses predominated for two consecutive seasons and were followed by an HRSV-B dominant season. Phylogenetic analysis based on glycoprotein G gene partial sequences revealed that viruses of both groups belonged to the worldwide dominant genotypes NA1 (HRSV-A) and BA-IV (HRSV-B). High diversity of this gene was driven only partially by selection pressure, as only two positively selected sites were identified in each group. Two of the HRSV-A isolates in this study contained a 72-nt duplication in the C-terminal end of the G gene (genotype ON1) that was first described in Canada in the 2010-2011 season. Initial spatial and temporal dynamics of this novel genotype were reconstructed by discrete phylogeographic analysis. Fifteen years after acquiring comparable 60-nt duplication in the G gene, genotype BA lineages have replaced all other HRSV-B strains. However, the population size of genotype ON1 plateaued soon and even decreased slightly before the beginning of the 2012-2013 season. © 2013 Wiley Periodicals, Inc.

  11. Extracts of Magnoliae flos inhibit inducible nitric oxide synthase via ERK in human respiratory epithelial cells.

    Science.gov (United States)

    Baek, Jin Ah; Lee, Yang Deok; Lee, Chan Bog; Go, Hyeon Kyu; Kim, Jin Pyo; Seo, Jeong Ju; Rhee, Yang Keun; Kim, A Mi; Na, Dong Jib

    2009-03-01

    Nitric oxide (NO) is a marker of pulmonary inflammation. In asthma, the levels of exhaled NO are elevated and the source of this increased NO is inducible nitric oxide synthase (iNOS) within airway epithelial cells. Epimagnolin and fargesin are compounds isolated from the ethanol extract of Magnoliae flos, the seed of the Magnolia plant and are used to treat nasal congestion, headache and sinusitis in Asian countries. This study investigated whether epimagnolin and fargesin inhibit extracellular signal-regulated kinase (ERK) activation and decrease iNOS expression and NO production in stimulated human respiratory epithelial cells. An immortal Type II alveolar cell line of human origin (A549) was stimulated by cytomix (CM), composed of IL-1beta, TNF-alpha and IFN-gamma, with or without concurrent exposure to M. flos extract (epimagnolin or fargesin). CM-induced levels of NO production, iNOS expression and ERK activation were evaluated. A549 cells stimulated with CM showed increases in iNOS mRNA and protein expression, and NO synthesis. However, treatment with epimagnolin or fargesin decreased levels of iNOS mRNA and protein expression, and NO synthesis. CM stimulated a rapid increase in the activity of ERK, whereas epimagnolin and fargesin inhibited ERK phosphorylation. Epimagnolin and fargesin inhibit iNOS expression and decrease production of NO via ERK pathway in cytokine-stimulated human respiratory epithelial cells.

  12. A semi-Markov chain approach to modeling respiratory patterns prior to extubation in preterm infants.

    Science.gov (United States)

    Onu, Charles C; Kanbar, Lara J; Shalish, Wissam; Brown, Karen A; Sant'Anna, Guilherme M; Kearney, Robert E; Precup, Doina

    2017-07-01

    After birth, extremely preterm infants often require specialized respiratory management in the form of invasive mechanical ventilation (IMV). Protracted IMV is associated with detrimental outcomes and morbidities. Premature extubation, on the other hand, would necessitate reintubation which is risky, technically challenging and could further lead to lung injury or disease. We present an approach to modeling respiratory patterns of infants who succeeded extubation and those who required reintubation which relies on Markov models. We compare the use of traditional Markov chains to semi-Markov models which emphasize cross-pattern transitions and timing information, and to multi-chain Markov models which can concisely represent non-stationarity in respiratory behavior over time. The models we developed expose specific, unique similarities as well as vital differences between the two populations.

  13. A closed-loop model of the respiratory system: focus on hypercapnia and active expiration.

    Science.gov (United States)

    Molkov, Yaroslav I; Shevtsova, Natalia A; Park, Choongseok; Ben-Tal, Alona; Smith, Jeffrey C; Rubin, Jonathan E; Rybak, Ilya A

    2014-01-01

    Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal "expiratory" muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model

  14. A closed-loop model of the respiratory system: focus on hypercapnia and active expiration.

    Directory of Open Access Journals (Sweden)

    Yaroslav I Molkov

    Full Text Available Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal "expiratory" muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2 exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient

  15. A finite state model for respiratory motion analysis in image guided radiation therapy

    International Nuclear Information System (INIS)

    Wu Huanmei; Sharp, Gregory C; Salzberg, Betty; Kaeli, David; Shirato, Hiroki; Jiang, Steve B

    2004-01-01

    Effective image guided radiation treatment of a moving tumour requires adequate information on respiratory motion characteristics. For margin expansion, beam tracking and respiratory gating, the tumour motion must be quantified for pretreatment planning and monitored on-line. We propose a finite state model for respiratory motion analysis that captures our natural understanding of breathing stages. In this model, a regular breathing cycle is represented by three line segments, exhale, end-of-exhale and inhale, while abnormal breathing is represented by an irregular breathing state. In addition, we describe an on-line implementation of this model in one dimension. We found this model can accurately characterize a wide variety of patient breathing patterns. This model was used to describe the respiratory motion for 23 patients with peak-to-peak motion greater than 7 mm. The average root mean square error over all patients was less than 1 mm and no patient has an error worse than 1.5 mm. Our model provides a convenient tool to quantify respiratory motion characteristics, such as patterns of frequency changes and amplitude changes, and can be applied to internal or external motion, including internal tumour position, abdominal surface, diaphragm, spirometry and other surrogates

  16. A finite state model for respiratory motion analysis in image guided radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu Huanmei [College of Computer and Information Science, Northeastern University, Boston, MA 02115 (United States); Sharp, Gregory C [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 (United States); Salzberg, Betty [College of Computer and Information Science, Northeastern University, Boston, MA 02115 (United States); Kaeli, David [Department of Electrical and Computer Engineering, Northeastern University, Boston, MA 02115 (United States); Shirato, Hiroki [Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo (Japan); Jiang, Steve B [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 (United States)

    2004-12-07

    Effective image guided radiation treatment of a moving tumour requires adequate information on respiratory motion characteristics. For margin expansion, beam tracking and respiratory gating, the tumour motion must be quantified for pretreatment planning and monitored on-line. We propose a finite state model for respiratory motion analysis that captures our natural understanding of breathing stages. In this model, a regular breathing cycle is represented by three line segments, exhale, end-of-exhale and inhale, while abnormal breathing is represented by an irregular breathing state. In addition, we describe an on-line implementation of this model in one dimension. We found this model can accurately characterize a wide variety of patient breathing patterns. This model was used to describe the respiratory motion for 23 patients with peak-to-peak motion greater than 7 mm. The average root mean square error over all patients was less than 1 mm and no patient has an error worse than 1.5 mm. Our model provides a convenient tool to quantify respiratory motion characteristics, such as patterns of frequency changes and amplitude changes, and can be applied to internal or external motion, including internal tumour position, abdominal surface, diaphragm, spirometry and other surrogates.

  17. Modeling of respiratory system dysfunction among nuclear workers: a preliminary study.

    Science.gov (United States)

    Belyaeva, Z D; Osovets, S V; Scott, B R; Zhuntova, G V; Grigoryeva, E S

    2008-01-01

    Numerous studies have reported on cancers among Mayak Production Association (PA) nuclear workers. Other studies have reported on serious deterministic effects of large radiation doses for the same population. This study relates to deterministic effects (respiratory system dysfunction) in Mayak workers after relatively small chronic radiation doses (alpha plus gamma). Because cigarette smoke is a confounding factor, we also account for smoking effects. Here we present a new empirical mathematical model that was introduced for simultaneous assessment of radiation and cigarette-smoking-related damage to the respiratory system. The model incorporates absolute thresholds for smoking- and radiation-induced respiratory system dysfunction. As the alpha radiation dose to the lung increased from 0 to 4.36 Gy, respiratory function indices studied decreased, although remaining in the normal range. The data were consistent with the view that alpha radiation doses to the lung above a relatively small threshold (0.15 to 0.39 Gy) cause some respiratory system dysfunction. Respiratory function indices were not found to be influenced by total-body gamma radiation doses in the range 0-3.8 Gy when delivered at low rates over years. However, significant decreases in airway conductance were found to be associated with cigarette smoking. Whether the indicated cigarette smoking and alpha radiation associated dysfunction is debilitating is unclear.

  18. Patient specific respiratory motion modeling using a limited number of 3D lung CT images.

    Science.gov (United States)

    Cui, Xueli; Gao, Xin; Xia, Wei; Liu, Yangchuan; Liang, Zhiyuan

    2014-01-01

    To build a patient specific respiratory motion model with a low dose, a novel method was proposed that uses a limited number of 3D lung CT volumes with an external respiratory signal. 4D lung CT volumes were acquired for patients with in vitro labeling on the upper abdominal surface. Meanwhile, 3D coordinates of in vitro labeling were measured as external respiratory signals. A sequential correspondence between the 4D lung CT and the external respiratory signal was built using the distance correlation method, and a 3D displacement for every registration control point in the CT volumes with respect to time can be obtained by the 4D lung CT deformable registration. A temporal fitting was performed for every registration control point displacements and an external respiratory signal in the anterior-posterior direction respectively to draw their fitting curves. Finally, a linear regression was used to fit the corresponding samples of the control point displacement fitting curves and the external respiratory signal fitting curve to finish the pulmonary respiration modeling. Compared to a B-spline-based method using the respiratory signal phase, the proposed method is highly advantageous as it offers comparable modeling accuracy and target modeling error (TME); while at the same time, the proposed method requires 70% less 3D lung CTs. When using a similar amount of 3D lung CT data, the mean of the proposed method's TME is smaller than the mean of the PCA (principle component analysis)-based methods' TMEs. The results indicate that the proposed method is successful in striking a balance between modeling accuracy and number of 3D lung CT volumes.

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

    Science.gov (United States)

    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.

  20. A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Chang-Sei eKim

    2016-02-01

    Full Text Available The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions.

  1. Prevalence and phylogenetic characterization of human enterovirus D68 among children with respiratory infection in Hong Kong.

    Science.gov (United States)

    Lam, Ho-Yin; Wong, Anthony Tsz-Chun; Tsao, Yen-Chow; Tang, Bone Siu-Fai

    2016-06-01

    This is the first report on the prevalence of human enterovirus D68 (EV-D68) among children with respiratory infection in Hong Kong. Among 1461 respiratory samples taken in 2014, EV-D68 was identified in 24 (1.64%) of them with a unusual seasonal pattern. Phylogenetic analysis indicated that all EV-D68 detected in this study belong to clade B. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Validation of statistical models for estimating hospitalization associated with influenza and other respiratory viruses.

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    Lin Yang

    Full Text Available BACKGROUND: Reliable estimates of disease burden associated with respiratory viruses are keys to deployment of preventive strategies such as vaccination and resource allocation. Such estimates are particularly needed in tropical and subtropical regions where some methods commonly used in temperate regions are not applicable. While a number of alternative approaches to assess the influenza associated disease burden have been recently reported, none of these models have been validated with virologically confirmed data. Even fewer methods have been developed for other common respiratory viruses such as respiratory syncytial virus (RSV, parainfluenza and adenovirus. METHODS AND FINDINGS: We had recently conducted a prospective population-based study of virologically confirmed hospitalization for acute respiratory illnesses in persons <18 years residing in Hong Kong Island. Here we used this dataset to validate two commonly used models for estimation of influenza disease burden, namely the rate difference model and Poisson regression model, and also explored the applicability of these models to estimate the disease burden of other respiratory viruses. The Poisson regression models with different link functions all yielded estimates well correlated with the virologically confirmed influenza associated hospitalization, especially in children older than two years. The disease burden estimates for RSV, parainfluenza and adenovirus were less reliable with wide confidence intervals. The rate difference model was not applicable to RSV, parainfluenza and adenovirus and grossly underestimated the true burden of influenza associated hospitalization. CONCLUSION: The Poisson regression model generally produced satisfactory estimates in calculating the disease burden of respiratory viruses in a subtropical region such as Hong Kong.

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

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    Ahmed A. Abdulhaq

    2017-01-01

    Full Text Available 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.

  4. Changes in relative fit of human heat stress indices to cardiovascular, respiratory, and renal hospitalizations across five Australian urban populations

    Science.gov (United States)

    Goldie, James; Alexander, Lisa; Lewis, Sophie C.; Sherwood, Steven C.; Bambrick, Hilary

    2018-03-01

    Various human heat stress indices have been developed to relate atmospheric measures of extreme heat to human health impacts, but the usefulness of different indices across various health impacts and in different populations is poorly understood. This paper determines which heat stress indices best fit hospital admissions for sets of cardiovascular, respiratory, and renal diseases across five Australian cities. We hypothesized that the best indices would be largely dependent on location. We fit parent models to these counts in the summers (November-March) between 2001 and 2013 using negative binomial regression. We then added 15 heat stress indices to these models, ranking their goodness of fit using the Akaike information criterion. Admissions for each health outcome were nearly always higher in hot or humid conditions. Contrary to our hypothesis that location would determine the best-fitting heat stress index, we found that the best indices were related largely by health outcome of interest, rather than location as hypothesized. In particular, heatwave and temperature indices had the best fit to cardiovascular admissions, humidity indices had the best fit to respiratory admissions, and combined heat-humidity indices had the best fit to renal admissions. With a few exceptions, the results were similar across all five cities. The best-fitting heat stress indices appear to be useful across several Australian cities with differing climates, but they may have varying usefulness depending on the outcome of interest. These findings suggest that future research on heat and health impacts, and in particular hospital demand modeling, could better reflect reality if it avoided "all-cause" health outcomes and used heat stress indices appropriate to specific diseases and disease groups.

  5. Changes in relative fit of human heat stress indices to cardiovascular, respiratory, and renal hospitalizations across five Australian urban populations

    Science.gov (United States)

    Goldie, James; Alexander, Lisa; Lewis, Sophie C.; Sherwood, Steven C.; Bambrick, Hilary

    2017-09-01

    Various human heat stress indices have been developed to relate atmospheric measures of extreme heat to human health impacts, but the usefulness of different indices across various health impacts and in different populations is poorly understood. This paper determines which heat stress indices best fit hospital admissions for sets of cardiovascular, respiratory, and renal diseases across five Australian cities. We hypothesized that the best indices would be largely dependent on location. We fit parent models to these counts in the summers (November-March) between 2001 and 2013 using negative binomial regression. We then added 15 heat stress indices to these models, ranking their goodness of fit using the Akaike information criterion. Admissions for each health outcome were nearly always higher in hot or humid conditions. Contrary to our hypothesis that location would determine the best-fitting heat stress index, we found that the best indices were related largely by health outcome of interest, rather than location as hypothesized. In particular, heatwave and temperature indices had the best fit to cardiovascular admissions, humidity indices had the best fit to respiratory admissions, and combined heat-humidity indices had the best fit to renal admissions. With a few exceptions, the results were similar across all five cities. The best-fitting heat stress indices appear to be useful across several Australian cities with differing climates, but they may have varying usefulness depending on the outcome of interest. These findings suggest that future research on heat and health impacts, and in particular hospital demand modeling, could better reflect reality if it avoided "all-cause" health outcomes and used heat stress indices appropriate to specific diseases and disease groups.

  6. Cytotoxicity of carbon nanohorns in different human cells of the respiratory system.

    Science.gov (United States)

    Schramm, Franziska; Lange, Martina; Hoppmann, Pia; Heutelbeck, Astrid

    2016-01-01

    One of the new synthetic carbon-based nanomaterials is carbon nanohorns (CNH). A potential risk for employees of production processes is an unintentional intake of these nanomaterials via inhalation. Once taken up, nanoparticles might interact with cells of different tissues as well as with intercellular substances. These interactions may have far-reaching consequences for human health. Currently, many gaps in available information on the CNH toxicological profile remain. The aim of this study was to determine the cytotoxicity of CNH particles on human epithelial cells of the respiratory system with special consideration given to different particle sizes. In all cell lines, cell viability was reduced after 24 h of exposure up to 60% and metabolic activity as evidenced by mitochondrial activity was lowered to 9% at a concentration of 1 g/L. The three respiratory cell lines differed in their sensitivity. The most robust cells were the bronchial epithelial cells. Further, particle size fractions induced different adverse effect strength, whereby no correlation between particle size fraction and toxicity was found. These findings demonstrate the need for further information regarding the behavior and effect strength of nanomaterial. To avoid the production of new harmful materials, a more comprehensive integration of results from toxicity studies in the development processes of engineered nanomaterials is recommended not only from an occupational viewpoint but also from an environmental perspective.

  7. Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema

    Science.gov (United States)

    Ford, N. L.; Martin, E. L.; Lewis, J. F.; Veldhuizen, R. A. W.; Holdsworth, D. W.; Drangova, M.

    2009-04-01

    Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

  8. Visualisation of time-varying respiratory system elastance in experimental ARDS animal models.

    Science.gov (United States)

    van Drunen, Erwin J; Chiew, Yeong Shiong; Pretty, Christopher; Shaw, Geoffrey M; Lambermont, Bernard; Janssen, Nathalie; Chase, J Geoffrey; Desaive, Thomas

    2014-03-02

    Patients with acute respiratory distress syndrome (ARDS) risk lung collapse, severely altering the breath-to-breath respiratory mechanics. Model-based estimation of respiratory mechanics characterising patient-specific condition and response to treatment may be used to guide mechanical ventilation (MV). This study presents a model-based approach to monitor time-varying patient-ventilator interaction to guide positive end expiratory pressure (PEEP) selection. The single compartment lung model was extended to monitor dynamic time-varying respiratory system elastance, Edrs, within each breathing cycle. Two separate animal models were considered, each consisting of three fully sedated pure pietrain piglets (oleic acid ARDS and lavage ARDS). A staircase recruitment manoeuvre was performed on all six subjects after ARDS was induced. The Edrs was mapped across each breathing cycle for each subject. Six time-varying, breath-specific Edrs maps were generated, one for each subject. Each Edrs map shows the subject-specific response to mechanical ventilation (MV), indicating the need for a model-based approach to guide MV. This method of visualisation provides high resolution insight into the time-varying respiratory mechanics to aid clinical decision making. Using the Edrs maps, minimal time-varying elastance was identified, which can be used to select optimal PEEP. Real-time continuous monitoring of in-breath mechanics provides further insight into lung physiology. Therefore, there is potential for this new monitoring method to aid clinicians in guiding MV treatment. These are the first such maps generated and they thus show unique results in high resolution. The model is limited to a constant respiratory resistance throughout inspiration which may not be valid in some cases. However, trends match clinical expectation and the results highlight both the subject-specificity of the model, as well as significant inter-subject variability.

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

    Science.gov (United States)

    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

  10. Variability in respiratory rhythm generation: In vitro and in silico models

    Science.gov (United States)

    Fietkiewicz, Christopher; Shafer, Geoffrey O.; Platt, Ethan A.; Wilson, Christopher G.

    2016-03-01

    The variability inherent in physiological rhythms is disruptive in extremis (too great or too little) but may also serve a functional and important role in homeostatic systems. Here we focus on the neural control of respiration which is critical for survival in many animals. The overall respiratory control system is comprised of multiple nuclei, each of which may have different contributions to rhythm variability. We focused on the pre-Bötzinger complex (preBötC) which is unique in that it can be studied in vitro as an isolated nucleus with autorhythmic behavior. The in vitro results show a bounded range of variability in which the upper and lower limits are functions of the respiratory rate. In addition, the correlation between variability and respiratory rate changes during development. We observed a weaker correlation in younger animals (0-3 days old) as compared to older animals (4-5 days old). Based on experimental observations, we developed a computational model that can be embedded in more comprehensive models of respiratory and cardiovascular autonomic control. Our simulation results successfully reproduce the variability we observed experimentally. The in silico model suggests that age-dependent variability may be due to a developmental increase in mean synaptic conductance between preBötC neurons. We also used simulations to explore the effects of stochastic spiking in sensory relay neurons. Our results suggest that stochastic spiking may actually stabilize modulation of both respiratory rate and its variability when the rate changes due to physiological demand.

  11. Noninvasive evaluation of respiratory muscles in pre-clinical model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Daniela M. Oliveira

    2016-04-01

    Full Text Available Abstract Since respiratory insufficiency is the main cause of death in patients affected by Duchenne Muscular Dystrophy (DMD, the present study aims at establishing a new non-invasive method to evaluate the clinical parameters of respiratory conditions of experimental models affected by DMD. With this purpose in mind, we evaluated the cardiorespiratory clinical conditions, the changes in the intercostal muscles, the diaphragmatic mobility, and the respiratory cycles in Golden Retriever Muscular Dystrophy (GRMD employing ultrasonography (US. A control group consisting of dogs of the same race, but not affected by muscular dystrophy, were used in this study. The results showed that inspiration, expiration and plateau movements (diaphragm mobility were lower in the affected group. Plateau phase in the affected group was practically non-existent and showed that the diaphragm remained in constant motion. Respiratory rate reached 15.5 per minute for affected group and 26.93 per minute for the control group. Expiration and inspiration movements of intercostal muscles reached 8.99mm and 8.79mm, respectively, for control group and 7.42mm and 7.40mm, respectively, for affected group. Methodology used in the present analysis proved to be viable for the follow-up and evaluation of the respiratory model in GRMD and may be adapted to other muscular dystrophy experimental models.

  12. Impact loading and locomotor-respiratory coordination significantly influence breathing dynamics in running humans.

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    Monica A Daley

    Full Text Available Locomotor-respiratory coupling (LRC, phase-locking between breathing and stepping rhythms, occurs in many vertebrates. When quadrupedal mammals gallop, 1∶1 stride per breath coupling is necessitated by pronounced mechanical interactions between locomotion and ventilation. Humans show more flexibility in breathing patterns during locomotion, using LRC ratios of 2∶1, 2.5∶1, 3∶1, or 4∶1 and sometimes no coupling. Previous studies provide conflicting evidence on the mechanical significance of LRC in running humans. Some studies suggest LRC improves breathing efficiency, but others suggest LRC is mechanically insignificant because 'step-driven flows' (ventilatory flows attributable to step-induced forces contribute a negligible fraction of tidal volume. Yet, although step-driven flows are brief, they cause large fluctuations in ventilatory flow. Here we test the hypothesis that running humans use LRC to minimize antagonistic effects of step-driven flows on breathing. We measured locomotor-ventilatory dynamics in 14 subjects running at a self-selected speed (2.6±0.1 ms(-1 and compared breathing dynamics in their naturally 'preferred' and 'avoided' entrainment patterns. Step-driven flows occurred at 1-2X step frequency with peak magnitudes of 0.97±0.45 Ls(-1 (mean ±S.D. Step-driven flows varied depending on ventilatory state (high versus low lung volume, suggesting state-dependent changes in compliance and damping of thoraco-abdominal tissues. Subjects naturally preferred LRC patterns that minimized antagonistic interactions and aligned ventilatory transitions with assistive phases of the step. Ventilatory transitions initiated in 'preferred' phases within the step cycle occurred 2x faster than those in 'avoided' phases. We hypothesize that humans coordinate breathing and locomotion to minimize antagonistic loading of respiratory muscles, reduce work of breathing and minimize rate of fatigue. Future work could address the potential

  13. Human airway xenograft models of epithelial cell regeneration

    Directory of Open Access Journals (Sweden)

    Puchelle Edith

    2000-10-01

    Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

  14. The Respiratory Impedance in an Asymmetric Model of the Lung Structure

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    Robin De Keyser

    2011-01-01

    Full Text Available This paper presents a model of the respiratory tree as a recurrent, but asymmetric, structure. The intrinsic properties posed by such a system lead to a multi-fractal structure, i.e. a non-integer order model of the total impedance. The fractional order behavior of the asymmetric tree simulated as a dynamic system is assessed by means of Bode plots, on a wide range of frequencies. The results indicate than in a specific frequency range, both the symmetric
    and asymmetric representation of the respiratory tree lead to similar values in the impedance.

  15. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013.

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    Rungnapa Malasao

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR. Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%, of which 305 (72.1% and 118 (27.9% were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05 and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines.

  16. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013.

    Science.gov (United States)

    Malasao, Rungnapa; Okamoto, Michiko; Chaimongkol, Natthawan; Imamura, Tadatsugu; Tohma, Kentaro; Dapat, Isolde; Dapat, Clyde; Suzuki, Akira; Saito, Mayuko; Saito, Mariko; Tamaki, Raita; Pedrera-Rico, Gay Anne Granada; Aniceto, Rapunzel; Quicho, Reynaldo Frederick Negosa; Segubre-Mercado, Edelwisa; Lupisan, Socorro; Oshitani, Hitoshi

    2015-01-01

    Human respiratory syncytial virus (HRSV) is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR). Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR) of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%), of which 305 (72.1%) and 118 (27.9%) were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (pPhilippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines.

  17. Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants.

    Science.gov (United States)

    Sacco, Randy E; McGill, Jodi L; Palmer, Mitchell V; Lippolis, John D; Reinhardt, Timothy A; Nonnecke, Brian J

    2012-12-01

    Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of calves with bovine RSV shares features in common with RSV infection in children, such as an age-dependent susceptibility. In addition, comparable microscopic lesions consisting of bronchiolar neutrophilic infiltrates, epithelial cell necrosis, and syncytial cell formation are observed. Further, our studies have shown an upregulation of pro-inflammatory mediators in RSV-infected calves, including IL-12p40 and CXCL8 (IL-8). This finding is consistent with increased levels of IL-8 observed in children with RSV bronchiolitis. Since rodents lack IL-8, neonatal calves can be useful for studies of IL-8 regulation in response to RSV infection. We have recently found that vitamin D in milk replacer diets can be manipulated to produce calves differing in circulating 25-hydroxyvitamin D3. The results to date indicate that although the vitamin D intracrine pathway is activated during RSV infection, pro-inflammatory mediators frequently inhibited by the vitamin D intacrine pathway in vitro are, in fact, upregulated or unaffected in lungs of infected calves. This review will summarize available data that provide parallels between bovine RSV infection in neonatal calves and human RSV in infants.

  18. Neonatal Calf Infection with Respiratory Syncytial Virus: Drawing Parallels to the Disease in Human Infants

    Directory of Open Access Journals (Sweden)

    Timothy A. Reinhardt

    2012-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of calves with bovine RSV shares features in common with RSV infection in children, such as an age-dependent susceptibility. In addition, comparable microscopic lesions consisting of bronchiolar neutrophilic infiltrates, epithelial cell necrosis, and syncytial cell formation are observed. Further, our studies have shown an upregulation of pro-inflammatory mediators in RSV-infected calves, including IL-12p40 and CXCL8 (IL-8. This finding is consistent with increased levels of IL-8 observed in children with RSV bronchiolitis. Since rodents lack IL-8, neonatal calves can be useful for studies of IL-8 regulation in response to RSV infection. We have recently found that vitamin D in milk replacer diets can be manipulated to produce calves differing in circulating 25-hydroxyvitamin D3. The results to date indicate that although the vitamin D intracrine pathway is activated during RSV infection, pro-inflammatory mediators frequently inhibited by the vitamin D intacrine pathway in vitro are, in fact, upregulated or unaffected in lungs of infected calves. This review will summarize available data that provide parallels between bovine RSV infection in neonatal calves and human RSV in infants.

  19. Inverse Modeling of Respiratory System during Noninvasive Ventilation by Maximum Likelihood Estimation

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    Esra Saatci

    2010-01-01

    Full Text Available We propose a procedure to estimate the model parameters of presented nonlinear Resistance-Capacitance (RC and the widely used linear Resistance-Inductance-Capacitance (RIC models of the respiratory system by Maximum Likelihood Estimator (MLE. The measurement noise is assumed to be Generalized Gaussian Distributed (GGD, and the variance and the shape factor of the measurement noise are estimated by MLE and Kurtosis method, respectively. The performance of the MLE algorithm is also demonstrated by the Cramer-Rao Lower Bound (CRLB with artificially produced respiratory signals. Airway flow, mask pressure, and lung volume are measured from patients with Chronic Obstructive Pulmonary Disease (COPD under the noninvasive ventilation and from healthy subjects. Simulations show that respiratory signals from healthy subjects are better represented by the RIC model compared to the nonlinear RC model. On the other hand, the Patient group respiratory signals are fitted to the nonlinear RC model with lower measurement noise variance, better converged measurement noise shape factor, and model parameter tracks. Also, it is observed that for the Patient group the shape factor of the measurement noise converges to values between 1 and 2 whereas for the Control group shape factor values are estimated in the super-Gaussian area.

  20. Novel treatment with neuroprotective and antiviral properties against a neuroinvasive human respiratory virus.

    Science.gov (United States)

    Brison, Elodie; Jacomy, Hélène; Desforges, Marc; Talbot, Pierre J

    2014-02-01

    Human coronaviruses (HCoVs) are recognized respiratory pathogens with neuroinvasive and neurotropic properties in mice and humans. HCoV strain OC43 (HCoV-OC43) can infect and persist in human neural cells and activate neuroinflammatory and neurodegenerative mechanisms, suggesting that it could be involved in neurological disease of unknown etiology in humans. Moreover, we have shown that HCoV-OC43 is neurovirulent in susceptible mice, causing encephalitis, and that a viral mutant with a single point mutation in the viral surface spike (S) protein induces a paralytic disease that involves glutamate excitotoxicity in susceptible mice. Herein, we show that glutamate recycling via the glial transporter 1 protein transporter and glutamine synthetase are central to the dysregulation of glutamate homeostasis and development of motor dysfunctions and paralytic disease in HCoV-OC43-infected mice. Moreover, memantine, an N-methyl-d-aspartate receptor antagonist widely used in the treatment of neurological diseases in humans, improved clinical scores related to paralytic disease and motor disabilities by partially restoring the physiological neurofilament phosphorylation state in virus-infected mice. Interestingly, memantine attenuated mortality rates and body weight loss and reduced HCoV-OC43 replication in the central nervous system in a dose-dependent manner. This novel action of memantine on viral replication strongly suggests that it could be used as an antiviral agent to directly limit viral replication while improving neurological symptoms in various neurological diseases with a viral involvement. Mutations in the surface spike (S) protein of human respiratory coronavirus OC43 appear after persistent infection of human cells of the central nervous system, a possible viral adaptation to this environment. Furthermore, a single amino acid change in the viral S protein modulated virus-induced neuropathology in mice from an encephalitis to a neuropathology characterized by

  1. Comparative study of erythromycin, amoxicillin and ampicillin antimicrobial activity against human respiratory tract pathogens.

    Science.gov (United States)

    Liss, R H; Norman, J C; Goldmann, D A

    1979-01-01

    An in vitro test system was used to compare the antimicrobial activity of erythromycin, amoxicillin and ampicillin against respiratory tract pathogens isolated from man. The minimum inhibitory concentrations (MICs) of fresh clinical isolates of Streptoccus pyogenes, Streptocuccus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to the macrolide and penicillins ranged between 0.01 and 0.9 microgram/ml. The microbes were exposed to each antibiotic for approximately 3 h at 1x,2x and 5x the relevant MIC. Irreversible surface defects and intracellular lesions were resolved by scanning and transmission electron microscopy in all antibiotic-treated bacterial species, irrespective of the antimicrobial used. In each case, inhibition of growth was recorded by turbometric assay; no significant difference was observed among the declining slopes of post-dosing growth curves for either erythromycin-, amoxicillin- or ampicillin-treated pathogens. The experimental observations show that the onset of antimicrobial activity and the bactericidal effectiveness of equipotent concentrations of erythromycin, amoxicillin and ampicillin were comparable in this study. The results complement previous clinical, bacteriologic and ultrastructure studies in vivo and demonstrate the contribution of the combined in vivo/in vitro study design for better understanding of antimicrobial activity in human respiratory tract infections.

  2. Effects of respiratory alkalosis on human skeletal muscle metabolism at the onset of submaximal exercise

    Science.gov (United States)

    LeBlanc, P J; Parolin, M L; Jones, N L; Heigenhauser, G J F

    2002-01-01

    The purpose of this study was to examine the effects of respiratory alkalosis on human skeletal muscle metabolism at rest and during submaximal exercise. Subjects exercised on two occasions for 15 min at 55 % of their maximal oxygen uptake while either hyperventilating (R-Alk) or breathing normally (Con). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to R-Alk. In the first minute of exercise, there was a delayed activation of pyruvate dehydrogenase (PDH) in R-Alk compared with Con, resulting in a reduced rate of pyruvate oxidation. Also, glycogenolysis was higher in R-Alk compared with Con, which was attributed to a higher availability of the monoprotonated form of inorganic phosphate (Pi), resulting in an elevated rate of pyruvate production. The mismatch between pyruvate production and its oxidation resulted in net lactate accumulation. These effects were not seen after 15 min of exercise, with no further differences in muscle metabolism between conditions. The results from the present study suggest that respiratory alkalosis may play an important role in lactate accumulation during the transition from rest to exercise in acute hypoxic conditions, but that other factors mediate lactate accumulation during steady-state exercise. PMID:12356901

  3. Human adenovirus detection among immunocompetent and immunocompromised patients presenting acute respiratory infection

    Directory of Open Access Journals (Sweden)

    Aripuana Watanabe

    2013-04-01

    Full Text Available INTRODUCTION: Human adenoviruses (HAdV play an important role in the etiology of severe acute lower respiratory infection, especially in immunocompromised individuals. The aim of the present study was detect the HAdV through different methods: direct fluorescence assay (DFA and nested-polymerase chain reaction (PCR-nested from patients with acute respiratory infection (ARI up to 7 days of symptoms onset. METHODS: Samples (n=643 were collected from different risk groups during from 2001 to 2010: 139 adults attended in an Emergency Room Patients (ERP; 205 health care workers (HCW; 69 from Renal Transplant Outpatients (RTO; 230 patients in hematopoietic stem cell transplantation (HSCT program. RESULTS: Among all patients (n=643 adenovirus was detected on 13.2% by DFA and/or PCR: 6/139 (4.3% adults from ERP, 7/205 (3.4% from HCW samples, 4/69 (5.8% from RTO and 68/230 (29.5% from HSCT patients. Nested PCR showed higher detection (10% compared to DFA test (3.8% (p < 0.001. HSCT patients presented significantly higher prevalence of HAdV infection. CONCLUSIONS: Adenovirus detection through nested-PCR assay was higher. However the inclusion of molecular method in laboratorial routine diagnostic should be evaluated considering the reality of each specific health service.

  4. Effects of surface material, ventilation, and human behavior on indirect contact transmission risk of respiratory infection.

    Science.gov (United States)

    Sze-To, Gin Nam; Yang, Yang; Kwan, Joseph K C; Yu, Samuel C T; Chao, Christopher Y H

    2014-05-01

    Infectious particles can be deposited on surfaces. Susceptible persons who contacted these contaminated surfaces may transfer the pathogens to their mucous membranes via hands, leading to a risk of respiratory infection. The exposure and infection risk contributed by this transmission route depend on indoor surface material, ventilation, and human behavior. In this study, quantitative infection risk assessments were used to compare the significances of these factors. The risks of three pathogens, influenza A virus, respiratory syncytial virus (RSV), and rhinovirus, in an aircraft cabin and in a hospital ward were assessed. Results showed that reducing the contact rate is relatively more effective than increasing the ventilation rate to lower the infection risk. Nonfabric surface materials were found to be much more favorable in the indirect contact transmission for RSV and rhinovirus than fabric surface materials. In the cases considered in this study, halving the ventilation rate and doubling the hand contact rate to surfaces and the hand contact rate to mucous membranes would increase the risk by 3.7-16.2%, 34.4-94.2%, and 24.1-117.7%, respectively. Contacting contaminated nonfabric surfaces may pose an indirect contact risk up to three orders of magnitude higher than that of contacting contaminated fabric surfaces. These findings provide more consideration for infection control and building environmental design. © 2013 Society for Risk Analysis.

  5. Testing Human Skin and Respiratory Sensitizers—What Is Good Enough?

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    Anki Malmborg

    2017-01-01

    Full Text Available Alternative methods for accurate in vitro assessment of skin and respiratory sensitizers are urgently needed. Sensitization is a complex biological process that cannot be evaluated accurately using single events or biomarkers, since the information content is too restricted in these measurements. On the contrary, if the tremendous information content harbored in DNA/mRNA could be mined, most complex biological processes could be elucidated. Genomic technologies available today, including transcriptional profiling and next generation sequencing, have the power to decipher sensitization, when used in the right context. Thus, a genomic test platform has been developed, denoted the Genomic Allergen Rapid Detection (GARD assay. Due to the high informational content of the GARD test, accurate predictions of both the skin and respiratory sensitizing capacity of chemicals, have been demonstrated. Based on a matured dendritic cell line, acting as a human-like reporter system, information about potency has also been acquired. Consequently, multiparametric diagnostic technologies are disruptive test principles that can change the way in which the next generation of alternative methods are designed.

  6. 4D motion models over the respiratory cycle for use in lung cancer radiotherapy planning

    Science.gov (United States)

    McClelland, J. R.; Chandler, A. G.; Blackall, J. M.; Ahmad, S.; Landau, D. B.; Hawkes, D. J.

    2005-04-01

    Respiratory motion causes problems of tumour localisation in radiotherapy treatment planning for lung cancer patients. We have developed a novel method of building patient specific motion models, which model the movement and non-rigid deformation of a lung tumour and surrounding lung tissue over the respiratory cycle. Free-breathing (FB) CT scans are acquired in cine mode, using 3 couch positions to acquire contiguous 'slabs' of 16 slices covering the region of interest. For each slab, 20 FB volumes are acquired over approx 20s. A reference volume acquired at Breath Hold (BH) and covering the whole lung, is non-rigidly registered to each of the FB volumes. The FB volumes are assigned a position in the respiratory cycle (PRC) calculated from the displacement of the chest wall. A motion model is then constructed for each slab, by fitting functions that temporally interpolate the registration results over the respiratory cycle. This can produce a prediction of the lung and tumour within the slab at any arbitrary PRC. The predictions for each of the slabs are then combined to produce a volume covering the whole region of interest. Results indicate that the motion modelling method shows considerable promise, offering significant improvement over current clinical practice, and potential advantages over alternative 4D CT imaging techniques. Using this framework, we examined and evaluated several different functions for performing the temporal interpolation. We believe the results of these comparisons will aid future model building for this and other applications.

  7. Development of an anesthetized rat model of exercise hyperpnoea: An integrative model of respiratory control using an equilibrium diagram.

    Science.gov (United States)

    Miyamoto, Tadayoshi; Manabe, Kou; Ueda, Shinya; Nakahara, Hidehiro

    2018-03-06

    What is the central question of this study? The lack of useful small animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise-induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anesthetized rat model for studying exercise hyperpnoea, using respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. Exercise-induced ventilatory abnormalities in various disease states seem to arise from pathological changes of the respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiologic basis in various disease models, the lack of integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anesthetized rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath-by-breath respiratory gas analysis data, and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end-tidal CO 2 pressure (P ETCO2 ) and minute ventilation (V E ), and the plant by the hyperbolic relationship between V E and P ETCO2 . During exercise, the controller curve shifted upward without change in controller gain, accompanying

  8. A novel swine model of ricin-induced acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Shahaf Katalan

    2017-02-01

    Full Text Available 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.

  9. Ferret respiratory system: clinical anatomy, physiology, and disease.

    Science.gov (United States)

    Johnson-Delaney, Cathy A; Orosz, Susan E

    2011-05-01

    The upper and lower respiratory tracts of ferrets have several similarities to humans, and therefore have been used as a research model for respiratory function. This article describes the clinical anatomy and physiology, and common respiratory diseases of the ferret. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Population pharmacodynamic modeling and simulation of the respiratory effect of acetazolamide in decompensated COPD patients.

    Directory of Open Access Journals (Sweden)

    Nicholas Heming

    Full Text Available Chronic obstructive pulmonary disease (COPD patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis.619 time-respiratory (minute ventilation, tidal volume and respiratory rate and 207 time-PaCO2 observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug.The effect of acetazolamide on minute ventilation and PaCO2 levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO2 levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily was required to significantly increase minute ventilation (P0.75 L min(-1 in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day.Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.

  11. Biological effects of desert dust in respiratory epithelial cells and a murine model.

    Science.gov (United States)

    Abstract As a result of the challenge of recent dust storms to public health, we tested the postulate that desert dust collected in the southwestern United States could impact a biological effect in respiratory epithelial cells and an animal model. Two samples of surface sedime...

  12. Respiratory mechanics

    CERN Document Server

    Wilson, Theodore A

    2016-01-01

    This book thoroughly covers each subfield of respiratory mechanics: pulmonary mechanics, the respiratory pump, and flow. It presents the current understanding of the field and serves as a guide to the scientific literature from the golden age of respiratory mechanics, 1960 - 2010. Specific topics covered include the contributions of surface tension and tissue forces to lung recoil, the gravitational deformation of the lung, and the interdependence forces that act on pulmonary airways and blood vessels. The geometry and kinematics of the ribs is also covered in detail, as well as the respiratory action of the external and internal intercostal muscles, the mechanics of the diaphragm, and the quantitative compartmental models of the chest wall is also described. Additionally, flow in the airways is covered thoroughly, including the wave-speed and viscous expiratory flow-limiting mechanisms; convection, diffusion and the stationary front; and the distribution of ventilation. This is an ideal book for respiratory ...

  13. Evaluating humidity recovery efficiency of currently available heat and moisture exchangers: a respiratory system model study

    Directory of Open Access Journals (Sweden)

    Jeanette Janaina Jaber Lucato

    2009-06-01

    Full Text Available OBJECTIVES: To evaluate and compare the efficiency of humidification in available heat and moisture exchanger models under conditions of varying tidal volume, respiratory rate, and flow rate. INTRODUCTION: Inspired gases are routinely preconditioned by heat and moisture exchangers to provide a heat and water content similar to that provided normally by the nose and upper airways. The absolute humidity of air retrieved from and returned to the ventilated patient is an important measurable outcome of the heat and moisture exchangers' humidifying performance. METHODS: Eight different heat and moisture exchangers were studied using a respiratory system analog. The system included a heated chamber (acrylic glass, maintained at 37°C, a preserved swine lung, a hygrometer, circuitry and a ventilator. Humidity and temperature levels were measured using eight distinct interposed heat and moisture exchangers given different tidal volumes, respiratory frequencies and flow-rate conditions. Recovery of absolute humidity (%RAH was calculated for each setting. RESULTS: Increasing tidal volumes led to a reduction in %RAH for all heat and moisture exchangers while no significant effect was demonstrated in the context of varying respiratory rate or inspiratory flow. CONCLUSIONS: Our data indicate that heat and moisture exchangers are more efficient when used with low tidal volume ventilation. The roles of flow and respiratory rate were of lesser importance, suggesting that their adjustment has a less significant effect on the performance of heat and moisture exchangers.

  14. Evaluating humidity recovery efficiency of currently available heat and moisture exchangers: a respiratory system model study.

    Science.gov (United States)

    Lucato, Jeanette Janaina Jaber; Adams, Alexander Bernard; Souza, Rogério; Torquato, Jamili Anbar; Carvalho, Carlos Roberto Ribeiro; Marini, John J

    2009-01-01

    To evaluate and compare the efficiency of humidification in available heat and moisture exchanger models under conditions of varying tidal volume, respiratory rate, and flow rate. Inspired gases are routinely preconditioned by heat and moisture exchangers to provide a heat and water content similar to that provided normally by the nose and upper airways. The absolute humidity of air retrieved from and returned to the ventilated patient is an important measurable outcome of the heat and moisture exchangers' humidifying performance. Eight different heat and moisture exchangers were studied using a respiratory system analog. The system included a heated chamber (acrylic glass, maintained at 37 degrees C), a preserved swine lung, a hygrometer, circuitry and a ventilator. Humidity and temperature levels were measured using eight distinct interposed heat and moisture exchangers given different tidal volumes, respiratory frequencies and flow-rate conditions. Recovery of absolute humidity (%RAH) was calculated for each setting. Increasing tidal volumes led to a reduction in %RAH for all heat and moisture exchangers while no significant effect was demonstrated in the context of varying respiratory rate or inspiratory flow. Our data indicate that heat and moisture exchangers are more efficient when used with low tidal volume ventilation. The roles of flow and respiratory rate were of lesser importance, suggesting that their adjustment has a less significant effect on the performance of heat and moisture exchangers.

  15. A novel modelling approach to energy transport in a respiratory system.

    Science.gov (United States)

    Nithiarasu, Perumal; Sazonov, Igor

    2017-10-01

    In this paper, energy transport in a respiratory tract is modelled using the finite element method for the first time. The upper and lower respiratory tracts are approximated as a 1-dimensional domain with varying cross-sectional and surface areas, and the radial heat conduction in the tissue is approximated using the 1-dimensional cylindrical coordinate system. The governing equations are solved using 1-dimensional linear finite elements with convective and evaporative boundary conditions on the wall. The results obtained for the exhalation temperature of the respiratory system have been compared with the available animal experiments. The study of a full breathing cycle indicates that evaporation is the main mode of heat transfer, and convection plays almost negligible role in the energy transport. This is in-line with the results obtained from animal experiments. Copyright © 2016 John Wiley & Sons, Ltd.

  16. A dynamic population-based model for the development of work-related respiratory health effects among bakery workers.

    NARCIS (Netherlands)

    Warren, N.; Meijster, T.; Heederik, D.; Tielemans, E.

    2009-01-01

    OBJECTIVES: This paper presents a dynamic population-based model for the development of sensitisation and respiratory symptoms in bakery workers. The model simulates a population of individual workers longitudinally and tracks the development of work-related sensitisation and respiratory symptoms in

  17. A dynamic population-based model for the development of work-related respiratory health effects among bakery workers

    NARCIS (Netherlands)

    Warren, N.; Meijster, T.; Heederik, D.; Tielemans, E.

    2009-01-01

    Objectives: This paper presents a dynamic population-based model for the development of sensitisation and respiratory symptoms in bakery workers. The model simulates a population of individual workers longitudinally and tracks the development of work-related sensitisation and respiratory symptoms in

  18. Investigating fractal property and respiratory modulation of human heartbeat time series using empirical mode decomposition.

    Science.gov (United States)

    Yeh, Jia-Rong; Sun, Wei-Zen; Shieh, Jiann-Shing; Huang, Norden E

    2010-06-01

    The human heartbeat interval reflects a complicated composition with different underlying modulations and the reactions against environmental inputs. As a result, the human heartbeat interval is a complex time series and its complexity can be scaled using various physical quantifications, such as the property of long-term correlation in detrended fluctuation analysis (DFA). Recently, empirical mode decomposition (EMD) has been shown to be a dyadic filter bank resembling those involved in wavelet decomposition. Moreover, the hierarchy of the extracted modes may be exploited for getting access to the Hurst exponent, which also reflects the property of long-term correlation for a stochastic time series. In this paper, we present significant findings for the dynamic properties of human heartbeat time series by EMD. According to our results, EMD provides a more accurate access to long-term correlation than Hurst exponent does. Moreover, the first intrinsic mode function (IMF 1) is an indicator of orderliness, which reflects the modulation of respiratory sinus arrhythmia (RSA) for healthy subjects or performs a characteristic component similar to that decomposed from a stochastic time series for subjects with congestive heart failure (CHF) and atrial fibrillation (AF). In addition, the averaged amplitude of IMF 1 acts as a parameter of RSA modulation, which reflects significantly negative correlation with aging. These findings lead us to a better understanding of the cardiac system. Copyright 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  19. Aerosol deposition doses in the human respiratory tree of electronic cigarette smokers.

    Science.gov (United States)

    Manigrasso, Maurizio; Buonanno, Giorgio; Fuoco, Fernanda Carmen; Stabile, Luca; Avino, Pasquale

    2015-01-01

    Aerosols from eight e-cigarettes at different nicotine levels and flavoring were characterized as particle number size distributions in the range 5.6-560 nm by FMPS and CPC. Results were used to provided osimetry estimates applying the MMPD model.Particle number concentrations varied between 3.26 x 10(9) and 4.09 x 10(9) part cm(-3) for e-liquids without nicotine and between 5.08 x 10(9) and 5.29 x 10(9) part cm(-3) for e-liquids with nicotine. No flavor effects were detected on particle concentration data. Particle size distributions were unimodal with modes between 107-165 nm and 165-255 nm, for number and volume metrics, respectively. Averagely, 6.25 x 10(10) particles were deposited in respiratory tree after a single puff. Highest deposition densities and mean layer thickness of e-cigarette liquid on the lung epithelium were estimated at lobar bronchi. Our study shows that e-cigarette aerosol is source of high particle dose in respiratory system, from 23%to 35% of the daily dose of a no-smoking individual.

  20. Mathematical models of human retina.

    Science.gov (United States)

    Tălu, Stefan

    2011-01-01

    To describe the human retina, due the absence of complete topographical data, mathematical models are required. The mathematical formula permits a relatively simple representation to explore the physical and optical characteristics of the retina, with particular parameters. Advanced mathematical models are applied for human vision studies, solid modelling and biomechanical behavior of the retina. The accurate modelling of the retina is important in the development of visual prostheses. The objective of this paper is to present an overview of researches for human retina modelling using mathematical models.

  1. Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study.

    Directory of Open Access Journals (Sweden)

    María Luz García-García

    Full Text Available 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

  2. Microbial volatile communication in human organotypic lung models.

    Science.gov (United States)

    Barkal, Layla J; Procknow, Clare L; Álvarez-García, Yasmín R; Niu, Mengyao; Jiménez-Torres, José A; Brockman-Schneider, Rebecca A; Gern, James E; Denlinger, Loren C; Theberge, Ashleigh B; Keller, Nancy P; Berthier, Erwin; Beebe, David J

    2017-11-24

    We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques, the model is designed to approximate the structure of the human bronchiole, containing airway, vascular, and extracellular matrix compartments. To complement direct infection of the organotypic bronchiole, we present a clickable extension that facilitates volatile compound communication between microbial populations and the host model. Using Aspergillus fumigatus, a respiratory pathogen, we characterize the inflammatory response of the organotypic bronchiole to infection. Finally, we demonstrate multikingdom, volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.

  3. Efficient solvers for coupled models in respiratory mechanics.

    Science.gov (United States)

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

    2017-02-01

    We present efficient preconditioners for one of the most physiologically relevant pulmonary models currently available. Our underlying motivation is to enable the efficient simulation of such a lung model on high-performance computing platforms in order to assess mechanical ventilation strategies and contributing to design more protective patient-specific ventilation treatments. The system of linear equations to be solved using the proposed preconditioners is essentially the monolithic system arising in fluid-structure interaction (FSI) extended by additional algebraic constraints. The introduction of these constraints leads to a saddle point problem that cannot be solved with usual FSI preconditioners available in the literature. The key ingredient in this work is to use the idea of the semi-implicit method for pressure-linked equations (SIMPLE) for getting rid of the saddle point structure, resulting in a standard FSI problem that can be treated with available techniques. The numerical examples show that the resulting preconditioners approach the optimal performance of multigrid methods, even though the lung model is a complex multiphysics problem. Moreover, the preconditioners are robust enough to deal with physiologically relevant simulations involving complex real-world patient-specific lung geometries. The same approach is applicable to other challenging biomedical applications where coupling between flow and tissue deformations is modeled with additional algebraic constraints. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Identification of a novel human papillomavirus by metagenomic analysis of samples from patients with febrile respiratory illness

    NARCIS (Netherlands)

    Mokili, J.L.; Dutilh, B.E.; Lim, Y.W.; Schneider, B.S.; Taylor, T.; Haynes, M.R.; Metzgar, D.; Myers, C.A.; Blair, P.J.; Nosrat, B.; Wolfe, N.D.; Rohwer, F.

    2013-01-01

    As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and

  5. The relation between air pollution and respiratory deaths in Tehran, Iran- using generalized additive models.

    Science.gov (United States)

    Dehghan, Azizallah; Khanjani, Narges; Bahrampour, Abbas; Goudarzi, Gholamreza; Yunesian, Masoud

    2018-03-20

    Some epidemiological evidence has shown a relation between ambient air pollution and adverse health outcomes. The aim of this study was to investigate the effect of air pollution on mortality from respiratory diseases in Tehran, Iran. In this ecological study, air pollution data was inquired from the Tehran Province Environmental Protection Agency and the Tehran Air Quality Control Company. Meteorological data was collected from the Tehran Meteorology Organization and mortality data from the Tehran Cemetery Mortality Registration. Generalized Additive Models (GAM) was used for data analysis with different lags, up to 15 days. A 10-unit increase in all pollutants except CO (1-unit) was used to compute the Relative Risk of deaths. During 2005 until 2014, 37,967 respiratory deaths occurred in Tehran in which 21,913 (57.7%) were male. The strongest relationship between NO 2 and PM 10 and respiratory death was seen on the same day (lag 0), and was respectively (RR = 1.04, 95% CI: 1.02-1.07) and (RR = 1.03, 95% CI: 1.02-1.04). O 3 and PM 2.5 had the strongest relationship with respiratory deaths on lag 2 and 1 respectively, and the RR was equal to 1.03, 95% CI: 1.01-1.05 and 1.06, 95% CI: 1.02-1.10 respectively. NO 2 , O 3 , PM 10 and PM 2.5 also showed significant relations with respiratory deaths in the older age groups. The findings of this study showed that O 3 , NO 2 , PM 10 and PM 2.5 air pollutants were related to respiratory deaths in Tehran. Reducing ambient air pollution can save lives in Tehran.

  6. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  7. Mycobacterium talmoniae sp. nov., a slowly growing mycobacterium isolated from human respiratory samples.

    Science.gov (United States)

    Davidson, Rebecca M; DeGroote, Mary Ann; Marola, Jamie L; Buss, Sarah; Jones, Victoria; McNeil, Michael R; Freifeld, Alison G; Elaine Epperson, L; Hasan, Nabeeh A; Jackson, Mary; Iwen, Peter C; Salfinger, Max; Strong, Michael

    2017-08-01

    A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a human respiratory sample in Nebraska, USA, in 2012. Analysis of the internal transcribed spacer sequence supported placement into the genus Mycobacterium with high sequence similarity to a previously undescribed strain isolated from a patient respiratory sample from Oregon, USA, held in a collection in Colorado, USA, in 2000. The two isolates were subjected to phenotypic testing and whole genome sequencing and found to be indistinguishable. The bacteria were acid-fast stain-positive, rod-shaped and exhibited growth after 7-10 days on solid media at temperatures ranging from 25 to 42°C. Colonies were non-pigmented, rough and slightly raised. Analyses of matrix-assisted laser desorption ionization time-of-flight profiles showed no matches against a reference library of 130 mycobacterial species. Full-length 16S rRNA gene sequences were identical for the two isolates, the average nucleotide identity (ANI) between their genomes was 99.7 % and phylogenetic comparisons classified the novel mycobacteria as the basal most species in the slowly growing Mycobacterium clade. Mycobacterium avium is the most closely related species based on rpoB gene sequence similarity (92 %), but the ANI between the genomes was 81.5 %, below the suggested cut-off for differentiating two species (95 %). Mycolic acid profiles were more similar to M. avium than to Mycobacterium simiae or Mycobacterium abscessus. The phenotypic and genomic data support the conclusion that the two related isolates represent a novel Mycobacterium species for which the name Mycobacterium talmoniae sp. nov. is proposed. The type strain is NE-TNMC-100812T (=ATCC BAA-2683T=DSM 46873T).

  8. Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils.

    Directory of Open Access Journals (Sweden)

    Giselle A Funchal

    Full Text Available Acute viral bronchiolitis by Respiratory Syncytial Virus (RSV is the most common respiratory illness in children in the first year of life. RSV bronchiolitis generates large numbers of hospitalizations and an important burden to health systems. Neutrophils and their products are present in the airways of RSV-infected patients who developed increased lung disease. Neutrophil Extracellular Traps (NETs are formed by the release of granular and nuclear contents of neutrophils in the extracellular space in response to different stimuli and recent studies have proposed a role for NETs in viral infections. In this study, we show that RSV particles and RSV Fusion protein were both capable of inducing NET formation by human neutrophils. Moreover, we analyzed the mechanisms involved in RSV Fusion protein-induced NET formation. RSV F protein was able to induce NET release in a concentration-dependent fashion with both neutrophil elastase and myeloperoxidase expressed on DNA fibers and F protein-induced NETs was dismantled by DNase treatment, confirming that their backbone is chromatin. This viral protein caused the release of extracellular DNA dependent on TLR-4 activation, NADPH Oxidase-derived ROS production and ERK and p38 MAPK phosphorylation. Together, these results demonstrate a coordinated signaling pathway activated by F protein that led to NET production. The massive production of NETs in RSV infection could aggravate the inflammatory symptoms of the infection in young children and babies. We propose that targeting the binding of TLR-4 by F protein could potentially lead to novel therapeutic approaches to help control RSV-induced inflammatory consequences and pathology of viral bronchiolitis.

  9. Prospective Evaluation of Rapid Antigen Tests for Diagnosis of Respiratory Syncytial Virus and Human Metapneumovirus Infections▿

    Science.gov (United States)

    Aslanzadeh, Jaber; Zheng, Xiaotian; Li, Haijing; Tetreault, Janice; Ratkiewicz, Irene; Meng, Shufang; Hamilton, Pamela; Tang, Yi-Wei

    2008-01-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two important viral pathogens that cause respiratory tract infections in the pediatric population. The rapid detection of these agents allows the prompt isolation and treatment of infected patients. In the present prospective study, we evaluated the performances of four rapid antigen detection assays, including a rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke, Hampshire, United Kingdom). The clinical specimens tested comprised 515 nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at Hartford Hospital from 1 November 2006 to 21 April 2007. Compared to the results of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of 79.8% and a specificity of 89.5%. The RSV DFA with Bartels reagents showed a sensitivity of 94.1% and a specificity of 96.8%. For hMPV, the sensitivity and specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and 100%, respectively, for the Imagen DFA. The hands-on and test turnaround times for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively. We conclude that while the RSV CIA is user-friendly, it lacks sensitivity and specificity, especially during off-peak months. In contrast, the RSV DFA is more sensitive and specific, but interpretation of its results is subjective and it demands technical time and expertise. Similarly, both hMPV DFAs are highly specific in comparison to the results of RT-PCR, but their sensitivities await further improvements. PMID:18337386

  10. Prospective evaluation of rapid antigen tests for diagnosis of respiratory syncytial virus and human metapneumovirus infections.

    Science.gov (United States)

    Aslanzadeh, Jaber; Zheng, Xiaotian; Li, Haijing; Tetreault, Janice; Ratkiewicz, Irene; Meng, Shufang; Hamilton, Pamela; Tang, Yi-Wei

    2008-05-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two important viral pathogens that cause respiratory tract infections in the pediatric population. The rapid detection of these agents allows the prompt isolation and treatment of infected patients. In the present prospective study, we evaluated the performances of four rapid antigen detection assays, including a rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke, Hampshire, United Kingdom). The clinical specimens tested comprised 515 nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at Hartford Hospital from 1 November 2006 to 21 April 2007. Compared to the results of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of 79.8% and a specificity of 89.5%. The RSV DFA with Bartels reagents showed a sensitivity of 94.1% and a specificity of 96.8%. For hMPV, the sensitivity and specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and 100%, respectively, for the Imagen DFA. The hands-on and test turnaround times for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively. We conclude that while the RSV CIA is user-friendly, it lacks sensitivity and specificity, especially during off-peak months. In contrast, the RSV DFA is more sensitive and specific, but interpretation of its results is subjective and it demands technical time and expertise. Similarly, both hMPV DFAs are highly specific in comparison to the results of RT-PCR, but their sensitivities await further improvements.

  11. El Bocavirus humano: un nuevo virus respiratorio Human bocavirus: a new respiratory virus

    Directory of Open Access Journals (Sweden)

    Carlos Aguirre Muñoz

    2006-01-01

    Full Text Available Las infecciones respiratorias agudas son una causa muy importante de morbilidad y mortalidad, especialmente en los niños y en los países en desarrollo. Con los métodos de laboratorio actuales, aproximadamente una tercera parte de estas infecciones se queda sin diagnóstico etiológico. Se acepta que los virus juegan un papel cardinal y que más de 200 virus, pertenecientes a seis familias virales están implicados en la génesis de este problema. La familia Parvoviridae se conoce desde mediados del siglo XX. El Parvovirus humano B19, identificado en 1980 y causante de enfermedades febriles y exantemáticas, fue considerado por muchos años como el único miembro de esta familia capaz de afectar a la especie humana. Sin embargo, un grupo de investigadores suecos comandado por Tobías Allander informó en agosto de 2005 el hallazgo de un nuevo Parvovirus, denominado provisionalmente Bocavirus humano, relacionado con infección respiratoria aguda en niños. En este artículo se resumen las características de este nuevo agente, se resalta la importancia de su hallazgo y de la técnica de investigación empleada. Respiratory tract infections are a leading cause of morbidity and mortality, mainly in children and also in developing countries. The aethiology of approximately 30% of these infections remains obscure, using current laboratory methods. It has been accepted that viruses play an important role and more than 200 viruses, belonging to 6 viral families are implied in the pathogenesis of this problem. Parvoviridae family has been known since the middle of the XX century. Human Parvovirus B19 was identified in 1980; it causes rashes and febrile diseases and it was considered for many years as the only member of this family able to affect humans. However, Dr. Tobias Allander and colleagues, at Karolinska Institut, have discovered a previously unknown parvovirus, called Human Bocavirus, that has been found to affect children, causing lower

  12. Identification of Burkholderia mallei and Burkholderia pseudomallei adhesins for human respiratory epithelial cells

    Directory of Open Access Journals (Sweden)

    Hogan Robert J

    2010-09-01

    Full Text Available Abstract Background Burkholderia pseudomallei and Burkholderia mallei cause the diseases melioidosis and glanders, respectively. A well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. In contrast, the means by which B. pseudomallei and B. mallei adhere to cells are poorly defined. The purpose of this study was to identify adherence factors expressed by these organisms. Results Comparative sequence analyses identified a gene product in the published genome of B. mallei strain ATCC23344 (locus # BMAA0649 that resembles the well-characterized Yersinia enterocolitica autotransporter adhesin YadA. The gene encoding this B. mallei protein, designated boaA, was expressed in Escherichia coli and shown to significantly increase adherence to human epithelial cell lines, specifically HEp2 (laryngeal cells and A549 (type II pneumocytes, as well as to cultures of normal human bronchial epithelium (NHBE. Consistent with these findings, disruption of the boaA gene in B. mallei ATCC23344 reduced adherence to all three cell types by ~50%. The genomes of the B. pseudomallei strains K96243 and DD503 were also found to contain boaA and inactivation of the gene in DD503 considerably decreased binding to monolayers of HEp2 and A549 cells and to NHBE cultures. A second YadA-like gene product highly similar to BoaA (65% identity was identified in the published genomic sequence of B. pseudomallei strain K96243 (locus # BPSL1705. The gene specifying this protein, termed boaB, appears to be B. pseudomallei-specific. Quantitative attachment assays demonstrated that recombinant E. coli expressing BoaB displayed greater binding to A549 pneumocytes, HEp2 cells and NHBE cultures. Moreover, a boaB mutant of B. pseudomallei DD503 showed decreased adherence to these respiratory cells. Additionally, a B. pseudomallei strain lacking expression of both boaA and boaB was impaired in its ability to

  13. Stochastic Models of Human Errors

    Science.gov (United States)

    Elshamy, Maged; Elliott, Dawn M. (Technical Monitor)

    2002-01-01

    Humans play an important role in the overall reliability of engineering systems. More often accidents and systems failure are traced to human errors. Therefore, in order to have meaningful system risk analysis, the reliability of the human element must be taken into consideration. Describing the human error process by mathematical models is a key to analyzing contributing factors. Therefore, the objective of this research effort is to establish stochastic models substantiated by sound theoretic foundation to address the occurrence of human errors in the processing of the space shuttle.

  14. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    International Nuclear Information System (INIS)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet; Quistgaard, Esben M.; Nordlund, Par; Thanabalu, Thirumaran; Torres, Jaume

    2015-01-01

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target

  15. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating

    International Nuclear Information System (INIS)

    Asenjo, Ana; Gonzalez-Armas, Juan C.; Villanueva, Nieves

    2008-01-01

    The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) β and protein phosphatase 2A (PP2A). Inhibition of lithium-sensitive kinase, soon after infection, blocks the viral growth cycle by inhibiting synthesis and/or accumulation of viral RNAs, proteins and extracellular particles. P protein phosphorylation at S54 is required to liberate viral ribonucleoproteins (RNPs) from M protein, during the uncoating process. Kinase inhibition, late in infection, produces a decrease in genomic RNA and infectious viral particles. LiCl, intranasally applied to mice infected with HRSV A2 strain, reduces the number of mice with virus in their lungs and the virus titre. Administration of LiCl to humans via aerosol should prevent HRSV infection, without secondary effects

  16. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Quistgaard, Esben M. [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Nordlund, Par [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Thanabalu, Thirumaran [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Torres, Jaume, E-mail: jtorres@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore)

    2015-08-15

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target.

  17. Influence of a Gas Exchange Correction Procedure on Resting Metabolic Rate and Respiratory Quotient in Humans.

    Science.gov (United States)

    Galgani, Jose E; Castro-Sepulveda, Mauricio A

    2017-11-01

    The aim of this study was to determine the influence of a gas exchange correction protocol on resting metabolic rate (RMR) and respiratory quotient (RQ), assessed by a Vmax Encore 29n metabolic cart (SensorMedics Co., Yorba Linda, California) in overnight fasted and fed humans, and to assess the predictive power of body size for corrected and uncorrected RMR. Healthy participants (23 M/29 F; 34 ± 9 years old; 26.3 ± 3.7 kg/m 2 ) ingested two 3-hour-apart glucose loads (75 g). Indirect calorimetry was conducted before and hourly over a 6-hour period. Immediately after indirect calorimetry assessment, gas exchange was simulated through high-precision mass-flow regulators, which permitted the correction of RMR and RQ values. Uncorrected and corrected RMR and RQ were directly related at each time over the 6-hour period. However, uncorrected versus corrected RMR was 6.9% ± 0.5% higher (128 ± 7 kcal/d; P exchange in humans over a 6-hour period is feasible and provides information of improved accuracy. © 2017 The Obesity Society.

  18. Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kailang; Li, Weikai; Peng, Guiqing; Li, Fang; (Harvard-Med); (UMM-MED)

    2010-03-04

    NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel {beta}-sandwich core structure consisting of 2 layers of {beta}-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a 'virus-binding hotspot' on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.

  19. Neonatal Calf Infection with Respiratory Syncytial Virus: Drawing Parallels to the Disease in Human Infants

    OpenAIRE

    Sacco, Randy E.; McGill, Jodi L.; Palmer, Mitchell V.; Lippolis, John D.; Reinhardt, Timothy A.; Nonnecke, Brian J.

    2012-01-01

    Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of ...

  20. Integrated Environmental Modelling: Human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  1. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  2. A dynamic model of human physiology

    Science.gov (United States)

    Green, Melissa; Kaplan, Carolyn; Oran, Elaine; Boris, Jay

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  3. Diaphragm remodeling and compensatory respiratory mechanics in a canine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Mead, A F; Petrov, M; Malik, A S; Mitchell, M A; Childers, M K; Bogan, J R; Seidner, G; Kornegay, J N; Stedman, H H

    2014-04-01

    Ventilatory insufficiency remains the leading cause of death and late stage morbidity in Duchenne muscular dystrophy (DMD). To address critical gaps in our knowledge of the pathobiology of respiratory functional decline, we used an integrative approach to study respiratory mechanics in a translational model of DMD. In studies of individual dogs with the Golden Retriever muscular dystrophy (GRMD) mutation, we found evidence of rapidly progressive loss of ventilatory capacity in association with dramatic morphometric remodeling of the diaphragm. Within the first year of life, the mechanics of breathing at rest, and especially during pharmacological stimulation of respiratory control pathways in the carotid bodies, shift such that the primary role of the diaphragm becomes the passive elastic storage of energy transferred from abdominal wall muscles, thereby permitting the expiratory musculature to share in the generation of inspiratory pressure and flow. In the diaphragm, this physiological shift is associated with the loss of sarcomeres in series (∼ 60%) and an increase in muscle stiffness (∼ 900%) compared with those of the nondystrophic diaphragm, as studied during perfusion ex vivo. In addition to providing much needed endpoint measures for assessing the efficacy of therapeutics, we expect these findings to be a starting point for a more precise understanding of respiratory failure in DMD.

  4. Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Yip, Ming Shum; Leung, Nancy Hiu Lan; Cheung, Chung Yan; Li, Ping Hung; Lee, Horace Hok Yeung; Daëron, Marc; Peiris, Joseph Sriyal Malik; Bruzzone, Roberto; Jaume, Martial

    2014-05-06

    Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages. We have used primary human immune cells to evaluate their susceptibility to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence microscopy and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were utilized to assess occurrence and consequences of infection. To gain insight into the underlying molecular mechanism, we performed mutational analysis with a series of truncated and chimeric constructs of fragment crystallizable γ receptors (FcγR), which bind antibody-coated pathogens. We show here that anti-Spike immune serum increased infection of human monocyte-derived macrophages by replication-competent SARS-CoV as well as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with SARS-CoV, however, did not support productive replication of the virus. Purified anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse immune serum, were sufficient to enhance infection. Antibody-mediated infection was dependent on signaling-competent members of the human FcγRII family, which were shown to confer susceptibility to otherwise naïve ST486 cells, as binding of immune complexes to cell surface FcγRII was necessary but not sufficient to trigger antibody-dependent enhancement (ADE) of infection. Furthermore, only FcγRII with intact cytoplasmic signaling domains were competent to sustain ADE of SARS-CoVpp infection, thus providing additional

  5. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

    Science.gov (United States)

    Iuliano, A Danielle; Roguski, Katherine M; Chang, Howard H; Muscatello, David J; Palekar, Rakhee; Tempia, Stefano; Cohen, Cheryl; Gran, Jon Michael; Schanzer, Dena; Cowling, Benjamin J; Wu, Peng; Kyncl, Jan; Ang, Li Wei; Park, Minah; Redlberger-Fritz, Monika; Yu, Hongjie; Espenhain, Laura; Krishnan, Anand; Emukule, Gideon; van Asten, Liselotte; Pereira da Silva, Susana; Aungkulanon, Suchunya; Buchholz, Udo; Widdowson, Marc-Alain; Bresee, Joseph S

    2017-12-14

    Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal

  6. Measurement of fractional order model parameters of respiratory mechanical impedance in total liquid ventilation.

    Science.gov (United States)

    Beaulieu, Alexandre; Bossé, Dominick; Micheau, Philippe; Avoine, Olivier; Praud, Jean-Paul; Walti, Hervé

    2012-02-01

    This study presents a methodology for applying the forced-oscillation technique in total liquid ventilation. It mainly consists of applying sinusoidal volumetric excitation to the respiratory system, and determining the transfer function between the delivered flow rate and resulting airway pressure. The investigated frequency range was f ∈ [0.05, 4] Hz at a constant flow amplitude of 7.5 mL/s. The five parameters of a fractional order lung model, the existing "5-parameter constant-phase model," were identified based on measured impedance spectra. The identification method was validated in silico on computer-generated datasets and the overall process was validated in vitro on a simplified single-compartment mechanical lung model. In vivo data on ten newborn lambs suggested the appropriateness of a fractional-order compliance term to the mechanical impedance to describe the low-frequency behavior of the lung, but did not demonstrate the relevance of a fractional-order inertance term. Typical respiratory system frequency response is presented together with statistical data of the measured in vivo impedance model parameters. This information will be useful for both the design of a robust pressure controller for total liquid ventilators and the monitoring of the patient's respiratory parameters during total liquid ventilation treatment. © 2011 IEEE

  7. Modeling Respiratory Gas Dynamics in the Aviator’s Breathing System. Volume 1

    Science.gov (United States)

    1994-05-01

    tricuspid valve which is presumed to track intrathoracic pressure. The pressures and flows in the various segments are coupled by their spatial connections...function in clinically significant pulmonary disease or for teaching respiratory physiology.’Ŗ’,13,14,15,16.17 Unfortunately, these were developed for...inspiratory valve model relates the flow and pressures between the mask supply hose and the oronasal cavity during inspiration. The expiratory valve

  8. Mathematical modeling and validation in physiology applications to the cardiovascular and respiratory systems

    CERN Document Server

    Bachar, Mostafa; Kappel, Franz

    2013-01-01

    This volume synthesizes theoretical and practical aspects of both the mathematical and life science viewpoints needed for modeling of the cardiovascular-respiratory system specifically and physiological systems generally.  Theoretical points include model design, model complexity and validation in the light of available data, as well as control theory approaches to feedback delay and Kalman filter applications to parameter identification. State of the art approaches using parameter sensitivity are discussed for enhancing model identifiability through joint analysis of model structure and data. Practical examples illustrate model development at various levels of complexity based on given physiological information. The sensitivity-based approaches for examining model identifiability are illustrated by means of specific modeling  examples. The themes presented address the current problem of patient-specific model adaptation in the clinical setting, where data is typically limited.

  9. A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition.

    Science.gov (United States)

    Kumar, Abhinav; Terakosolphan, Wachirun; Hassoun, Mireille; Vandera, Kalliopi-Kelli; Novicky, Astrid; Harvey, Richard; Royall, Paul G; Bicer, Elif Melis; Eriksson, Jonny; Edwards, Katarina; Valkenborg, Dirk; Nelissen, Inge; Hassall, Dave; Mudway, Ian S; Forbes, Ben

    2017-12-01

    To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays. The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF. SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution. The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.

  10. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

    Science.gov (United States)

    Cantin, A M; Fells, G A; Hubbard, R C; Crystal, R G

    1990-09-01

    We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-soluble fraction in the 100-300-kD range. Plasma proteins with anti-H2O2 properties were in insufficient concentrations to provide the antioxidant protection observed. However, catalase, a normal intracellular antioxidant, was present in sufficient concentration to account for most of the observed anti-H2O2 properties of ELF. Depletion of ELF with an anticatalase antibody abolished the anti-H2O2 macromolecular defenses of ELF. Since catalase is not normally released by cells, a likely explanation for its presence in high concentrations in normal ELF is that it is released by lung inflammatory and parenchymal cells onto the epithelial surface of the lower respiratory tract during their normal turnover and collects there due to the slow turnover of ELF. It is likely that catalase in the ELF of normal individuals plays a role in protecting lung parenchymal cells against oxidants present in the extracellular milieu.

  11. Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis

    Science.gov (United States)

    Measso do Bonfim, Caroline; Simão Sobrinho, João; Lacerda Nogueira, Rodrigo; Salgado Kupper, Daniel; Cardoso Pereira Valera, Fabiana; Lacerda Nogueira, Maurício; Villa, Luisa Lina; Rahal, Paula; Sichero, Laura

    2015-01-01

    A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied. PMID:26151558

  12. Endocytosis is required for exocytosis and priming of respiratory burst activity in human neutrophils.

    Science.gov (United States)

    Creed, T Michael; Tandon, Shweta; Ward, Richard A; McLeish, Kenneth R

    2017-10-01

    Neutrophil generation of reactive oxygen species (ROS) is enhanced by exposure to pro-inflammatory agents in a process termed priming. Priming is depending on exocytosis of neutrophil granules and p47 phox phosphorylation-dependent translocation of cytosolic NADPH oxidase components. Clathrin-mediated endocytosis was recently reported to be necessary for priming, but the mechanism linking endocytosis to priming was not identified. The present study examined the hypothesis that endocytosis regulates neutrophil priming by controlling granule exocytosis. Clathrin-mediated endocytosis by isolated human neutrophils was inhibited by chlorpromazine, monodansylcadaverine, and sucrose. Exocytosis of granule subsets was measured as release of granule components by ELISA or chemiluminescence. ROS generation was measured as extracellular release of superoxide as reduction of ferrocytochrome c. p38 MAPK activation and p47 phox phosphorylation were measured by immunoblot analysis. Statistical analysis was performed using a one-way ANOVA with the Tukey-Kramer multiple-comparison test. Inhibition of endocytosis prevented priming of superoxide release by TNFα and inhibited TNFα stimulation and priming of exocytosis of all four granule subsets. Inhibition of endocytosis did not reduce TNFα-stimulated p38 MAPK activation or p47 phox phosphorylation. Inhibition of NADPH oxidase activity blocked TNFα stimulation of secretory vesicle and gelatinase granule exocytosis. Endocytosis is linked to priming of respiratory burst activity through ROS-mediated control of granule exocytosis.

  13. Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

    Directory of Open Access Journals (Sweden)

    James V Lawler

    2006-05-01

    Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

  14. Influence of age on respiratory modulation of muscle sympathetic nerve activity, blood pressure and baroreflex function in humans.

    Science.gov (United States)

    Shantsila, Alena; McIntyre, David B; Lip, Gregory Y H; Fadel, Paul J; Paton, Julian F R; Pickering, Anthony E; Fisher, James P

    2015-09-01

    What is the central question of this study? Does ageing influence the respiratory-related bursting of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure (Traube-Hering waves) that occur with respiration? What is the main finding and its importance? Despite the age-related elevation in MSNA, the cyclical inhibition of MSNA during respiration is similar between young and older individuals. Furthermore, central respiratory-sympathetic coupling plays a role in the generation of Traube-Hering waves in both young and older humans. Healthy ageing and alterations in respiratory-sympathetic coupling have been independently linked with heightened sympathetic neural vasoconstrictor activity. We investigated how age influences the respiratory-related modulation of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure that occur with respiration (Traube-Hering waves; THW). Ten young (22 ± 2 years; mean ± SD) and 10 older healthy men (58 ± 6 years) were studied while resting supine and breathing spontaneously. MSNA, blood pressure and respiration were recorded simultaneously. Resting values were ascertained and respiratory cycle-triggered averaging of MSNA and blood pressure measurements performed. The MSNA burst incidence was higher in older individuals [22.7 ± 9.2 versus 42.2 ± 13.7 bursts (100 heart beats)(-1), P respiratory-related MSNA and the magnitude of Traube-Hering waves was observed in all young (100%) and most older subjects (80%). These data suggest that the strength of the cyclical inhibition of MSNA during respiration is similar between young and older individuals; thus, alterations in respiratory-sympathetic coupling appear not to contribute to the age-related elevation in MSNA. Furthermore, central respiratory-sympathetic coupling plays a role in the generation of Traube-Hering waves in both healthy young and older

  15. Human nasal turbinates as a viable source of respiratory epithelial cells using co-culture system versus dispase-dissociation technique.

    Science.gov (United States)

    Noruddin, Nur Adelina Ahmad; Saim, Aminuddin B; Chua, Kien Hui; Idrus, Ruszymah

    2007-12-01

    To compare a co-culture system with a conventional dispase-dissociation method for obtaining functional human respiratory epithelial cells from the nasal turbinates for tissue engineering application. Human respiratory epithelial cells were serially passaged using a co-culture system and a conventional dispase-dissociation technique. The growth kinetics and gene expression levels of the cultured respiratory epithelial cells were compared. Four genes were investigated, namely cytokeratin-18, a marker for ciliated and secretory epithelial cells; cytokeratin-14, a marker for basal epithelial cells; MKI67, a proliferation marker; and MUC5B, a marker for mucin secretion. Immunocytochemical analysis was performed using monoclonal antibodies against the high molecular-weight cytokeratin 34 beta E12, cytokeratin 18, and MUC5A to investigate the protein expression from cultured respiratory epithelial cells. Respiratory epithelial cells cultured using both methods maintained polygonal morphology throughout the passages. At passage 1, co-cultured respiratory epithelial showed a 2.6-times higher growth rate compared to conventional dispase dissociation technique, and 7.8 times higher at passage 2. Better basal gene expression was observed by co-cultured respiratory epithelial cells compared to dispase dissociated cells. Immunocytochemical analyses were positive for the respiratory epithelial cells cultured using both techniques. Co-culture system produced superior quality of cultured human respiratory epithelial cells from the nasal turbinates as compared to dispase dissociation technique.

  16. Respiratory flows during early childhood: Computational models to examine therapeutic aerosols in the developing airways

    Science.gov (United States)

    Tenenbaum-Katan, Janna; Hofemeier, Philipp; Sznitman, Josué; Janna Tenenbaum-Katan Team

    2015-11-01

    Inhalation therapy is the cornerstone of early-childhood respiratory treatments, as well as a rising potential for systemic drug delivery and pulmonary vaccination. As such, indispensable understanding of respiratory flow phenomena, coupled with particle transport at the deep regions of children's lungs is necessary to attain efficient targeting of aerosol therapy. However, fundamental research of pulmonary transport is overwhelmingly focused on adults. In our study, we have developed an anatomically-inspired computational model of representing pulmonary acinar regions at several age points during a child's development. Our numerical simulations examine respiratory flows and particle deposition maps within the acinar model, accounting for varying age dependant anatomical considerations and ventilation patterns. Resulting deposition maps of aerosols alter with age, such findings might suggest that medication protocols of inhalation therapy in young children should be considered to be accordingly amended with the child's development. Additionally to understanding basic scientific concepts of age effects on aerosol deposition, our research can potentially contribute practical guidelines to therapy protocols, and its' necessary modifications with age. We acknowledge the support of the ISF and the Israeli ministry of Science.

  17. 4D modeling and estimation of respiratory motion for radiation therapy

    CERN Document Server

    Lorenz, Cristian

    2013-01-01

    Respiratory motion causes an important uncertainty in radiotherapy planning of the thorax and upper abdomen. The main objective of radiation therapy is to eradicate or shrink tumor cells without damaging the surrounding tissue by delivering a high radiation dose to the tumor region and a dose as low as possible to healthy organ tissues. Meeting this demand remains a challenge especially in case of lung tumors due to breathing-induced tumor and organ motion where motion amplitudes can measure up to several centimeters. Therefore, modeling of respiratory motion has become increasingly important in radiation therapy. With 4D imaging techniques spatiotemporal image sequences can be acquired to investigate dynamic processes in the patient’s body. Furthermore, image registration enables the estimation of the breathing-induced motion and the description of the temporal change in position and shape of the structures of interest by establishing the correspondence between images acquired at different phases of the br...

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

    Science.gov (United States)

    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.

  19. Identification and genetic characterization of a novel circular single-stranded DNA virus in a human upper respiratory tract sample.

    Science.gov (United States)

    Cui, Lunbiao; Wu, Binyao; Zhu, Xiaojuan; Guo, Xiling; Ge, Yiyue; Zhao, Kangchen; Qi, Xian; Shi, Zhiyang; Zhu, Fengcai; Sun, Lixin; Zhou, Minghao

    2017-11-01

    Metagenomic analysis through high-throughput sequencing is a tool for detecting both known and novel viruses. Using this technique, a novel circular single-stranded DNA (ssDNA) virus genome was discovered in respiratory secretions from a febrile traveler. The virus, named human respiratory-associated PSCV-5-like virus (HRAPLV), has a genome comprising 3,018 bases, with two major putative ORFs inversely encoding capsid (Cap) and replicase (Rep) protein and separated by two intergenic regions. One stem-loop structure was predicted in the larger intergenic region (LIR). The predicted amino acid sequences of the Cap and Rep proteins of HRAPLV showed highest identity to those of porcine stool-associated circular virus 5 isolate CP3 (PoSCV 5) (53.0% and 48.9%, respectively). The host tropism of the virus is unknown, and further study is warranted to determine whether this novel virus is associated with human disease.

  20. Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy

    Directory of Open Access Journals (Sweden)

    Petrica-Adrian Panaite

    2013-05-01

    Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1. Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding

  1. Prevalence of Human Papillomavirus (HPV in upper respiratory tract mucosa in a group of pre-school children

    Directory of Open Access Journals (Sweden)

    Jaroslaw Szydłowski

    2014-11-01

    Full Text Available [b]introduction[/b]. Human Papillomavirus (HPV is a group of DNA viruses which is an etiological factor of many benign and malignant diseases of the upper respiratory tract mucosa, female genital tract and the skin. HPV infection is considered a sexually-transmitted infection, but can also be transmitted by non-sexual routes, including perinatal vertical transmission, physical contact, iatrogenic infection and autoinoculation. Recurrent Respiratory Papillomatosis (RRP in children is connected with HPV infection transmitted vertically from mother to child during the passage of the foetus through an infected birth canal. [b]objective. [/b]The aim of this study was to establish the level of Human Papillomaviruses carrier state in upper respiratory tract mucosa in healthy pre-school children, and to identify potential risk factors for HPV infection. [b]materials and method[/b]. After obtaining consent from their parents, 97 pre-school children were examined – 51 girls and 46 boys between the ages of 3 – 5 years; average age – 4 years and 5 months. 68 children were urban dwellers and 29 came from a rural environment. A questionnaire with detailed history was taken including parents’ and child`s personal data, as well as perinatal risk factors in pregnancy. Socio-demographic information was also obtained, including the standard of living, and chosen environmental factors. Routine ENT examination was performed. Exfoliated oral squamous cells were collected from swabs and analysed for the presence of DNA papillomaviruses by polymerase chain reaction. [b]results.[/b] The presence of HPV in the respiratory tract in children was detected in 19.6% cases. ‘High oncogenic potential’ HPVs, such as HPV-16 and HPV-18, were not observed in squamous cell mucosa of the respiratory tract in the children. No significant differences were observed between the HPV carrier state in urban and rural inhabitants.

  2. Blood flow index using near-infrared spectroscopy and indocyanine green as a minimally invasive tool to assess respiratory muscle blood flow in humans

    DEFF Research Database (Denmark)

    Guenette, Jordan A; Henderson, William R; Dominelli, Paolo B

    2011-01-01

    Near-infrared spectroscopy (NIRS) in combination with indocyanine green (ICG) dye has recently been used to measure respiratory muscle blood flow (RMBF) in humans. This method is based on the Fick principle and is determined by measuring ICG in the respiratory muscles using transcutaneous NIRS in...

  3. Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from Vietnamese children identifies distinct patterns of inter- and intra-host evolution

    NARCIS (Netherlands)

    Do, Lien Anh Ha; Wilm, Andreas; van Doorn, H. Rogier; Lam, Ha Minh; Sim, Shuzhen; Sukumaran, Rashmi; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; Chen, Swaine; Nagarajan, Niranjan; Bryant, Juliet E.; Hibberd, Martin Lloyd

    2015-01-01

    Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children under two years of age. Little is known about RSV intra-host genetic diversity over the course of infection, or about the immune pressures that drive RSV molecular evolution. We performed

  4. Analysis of Cigarette Smoke Deposition Within an In Vitro Exposure System for Simulating Exposure in the Human Respiratory Tract

    OpenAIRE

    Ishikawa Shinkichi; Nagata Yasufumi; Suzuki Takuya

    2016-01-01

    For the risk assessment of airborne chemicals, a variety of in vitro direct exposure systems have been developed to replicate airborne chemical exposure in vivo. Since cells at the air-liquid interface are exposed to cigarette smoke as an aerosol in direct exposure systems, it is possible to reproduce the situation of cigarette smoke exposure in the human respiratory system using this device. However it is difficult to know whether the exposed cigarette smoke in this system is consistent with...

  5. Micronutrient concentrations in respiratory syncytial virus and human metapneumovirus in Yemeni children

    NARCIS (Netherlands)

    Al-Sonboli, N.; Al-Aghbari, N.; Al-Aryani, A.; Atef, Z.; Brabin, B.; Shenkin, A.; Roberts, E.; Harper, G.; Hart, C. A.; Cuevas, L. E.

    2009-01-01

    BACKGROUND: Acute respiratory infections (ARI) cause significant childhood mortality. Nutritional homeostasis, particularly micronutrient levels, is important in modulating response to infection. More information is required regarding micronutrient levels in ARI viral infections, especially newly

  6. Human mobility: Models and applications

    Science.gov (United States)

    Barbosa, Hugo; Barthelemy, Marc; Ghoshal, Gourab; James, Charlotte R.; Lenormand, Maxime; Louail, Thomas; Menezes, Ronaldo; Ramasco, José J.; Simini, Filippo; Tomasini, Marcello

    2018-03-01

    Recent years have witnessed an explosion of extensive geolocated datasets related to human movement, enabling scientists to quantitatively study individual and collective mobility patterns, and to generate models that can capture and reproduce the spatiotemporal structures and regularities in human trajectories. The study of human mobility is especially important for applications such as estimating migratory flows, traffic forecasting, urban planning, and epidemic modeling. In this survey, we review the approaches developed to reproduce various mobility patterns, with the main focus on recent developments. This review can be used both as an introduction to the fundamental modeling principles of human mobility, and as a collection of technical methods applicable to specific mobility-related problems. The review organizes the subject by differentiating between individual and population mobility and also between short-range and long-range mobility. Throughout the text the description of the theory is intertwined with real-world applications.

  7. External Validation of Prediction Models for Pneumonia in Primary Care Patients with Lower Respiratory Tract Infection

    DEFF Research Database (Denmark)

    Schierenberg, Alwin; Minnaard, Margaretha C; Hopstaken, Rogier M

    2016-01-01

    BACKGROUND: Pneumonia remains difficult to diagnose in primary care. Prediction models based on signs and symptoms (S&S) serve to minimize the diagnostic uncertainty. External validation of these models is essential before implementation into routine practice. In this study all published S&S models...... for prediction of pneumonia in primary care were externally validated in the individual patient data (IPD) of previously performed diagnostic studies. METHODS AND FINDINGS: S&S models for diagnosing pneumonia in adults presenting to primary care with lower respiratory tract infection and IPD for validation were...... identified through a systematical search. Six prediction models and IPD of eight diagnostic studies (N total = 5308, prevalence pneumonia 12%) were included. Models were assessed on discrimination and calibration. Discrimination was measured using the pooled Area Under the Curve (AUC) and delta AUC...

  8. Sin-quadratic model for chest tomosynthesis respiratory signal analysis and its application in four dimensional chest tomosynthesis reconstruction.

    Science.gov (United States)

    Tao, Xi; Zhang, Hua; Qin, Genggeng; Ma, Jianhua; Feng, Qianjin; Chen, Wufan

    2018-02-01

    Chest tomosynthesis (CTS) is a newly developed imaging technique which provides pseudo-3D volume anatomical information of thorax from limited-angle projections and contains much less of superimposed anatomy than the chest X-ray radiography. One of the relatively common problems in CTS is the patient respiratory motion during image acquisition, which negatively impacts the detectability. In this work, we propose a sin-quadratic model to analyze the respiratory motion during CTS scan, which is a real time method where the respiratory signal is generated by extracting the motion of diaphragm from projection radiographs. According to the estimated respiratory signal, the CTS projections were then amplitude-based sorted into four to eight phases, and an iterative reconstruction strategy with total variation regularization was adopted to reconstruct the CTS images at each phase. Simulated digital XCAT phantom data and three sets of patient data were adopted for the experiments to validate the performance of the sin-quadratic model and its application in four dimensional (4D) CTS reconstruction. Results of the XCAT phantom simulation study show that the correlation coefficient between the extracted respiratory signal and the originally designed respiratory signal is 0.9964, which suggests that the proposed model could exactly extract the respiratory signal from CTS projections. The 4D CTS reconstructions of both the phantom data and the patient data show clear reduction of motion-induced blur. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

  9. Human papilloma virus vaccination in patients with an aggressive course of recurrent respiratory papillomatosis.

    Science.gov (United States)

    Hočevar-Boltežar, Irena; Matičič, Mojca; Sereg-Bahar, Maja; Gale, Nina; Poljak, Mario; Kocjan, Boštjan; Zargi, Miha

    2014-12-01

    In the case of an aggressive course of recurrent respiratory papillomatosis (RRP), adjuvant therapy can be used besides surgery. The aim of the study was to investigate the influence of vaccination with a quadrivalent vaccine against human papilloma viruses (HPV) types 6, 11, 16 and 18 on the course of RRP. Eleven subjects aged 13-46 years with a rapid growth of laryngeal papillomas were included in the study. They were vaccinated with three doses of the quadrivalent prophylactic HPV vaccine (Silgard(®), MSD) and followed up for 12-52 months. The intervals between the successive surgical procedures, the extension of the disease (Derkay score) at each surgery, and the number of surgical procedures per year before vaccination and after its completion were compared. The mean interval between the surgical procedures was 271.2 days before the vaccination and 537.4 days after it (p = 0.034). The mean number of surgeries per year was 2.16 before the vaccination and 0.93 after it (p = 0.022). The Derkay score did not change significantly after vaccination. Complete remission of the disease was observed in one patient, partial response to the vaccination was observed in seven patients and no response was observed in three patients. In conclusion, vaccination with the quadrivalent HPV vaccine can favorably influence the course of RRP in patients with the rapid growth of the papillomas. It significantly prolongs the intervals between the surgical procedures and reduces the number of procedures needed in the majority of patients. The present investigation can serve as a pilot study for further research. For a final conclusion a longer follow-up and studies on more patients are necessary.

  10. Respiratory acidosis

    Science.gov (United States)

    Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as ...

  11. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on

  12. Respiratory explants as a model to investigate early events of contagious bovine pleuropneumonia infection.

    Science.gov (United States)

    Di Teodoro, Giovanni; Marruchella, Giuseppe; Di Provvido, Andrea; Orsini, Gianluca; Ronchi, Gaetano Federico; D'Angelo, Anna Rita; D'Alterio, Nicola; Sacchini, Flavio; Scacchia, Massimo

    2018-01-12

    Contagious bovine pleuropneumonia (CBPP) is a severe disease caused by Mycoplasma mycoides subsp. mycoides (Mmm). Knowledge on CBPP pathogenesis is fragmented and hampered by the limited availability of laboratory animal and in vitro models of investigation. The purpose of the present study is to assess respiratory explants as useful tools to study the early stages of CBPP. Explants were obtained from trachea, bronchi and lungs of slaughtered cattle, tested negative for Mycoplasma spp. and for the major bacterial and viral respiratory pathogens. The interaction of Mmm with explant cells was studied by immunohistochemistry (IHC), double-labelling indirect immunofluorescence (DLIIF) and laser scanning confocal microscopy (LSCM). Mmm capability to survive and proliferate within the explants was evaluated by standard microbiological procedures. Finally, the putative cellular internalization of Mmm was further investigated by the gentamicin invasion assay. IHC and DLIIF indicated that Mmm can colonize explants, showing a marked tropism for lower airways. Specifically, Mmm was detected on/inside the bronchiolar and alveolar epithelial cells, the alveolar macrophages and the endothelial cells. The interaction between Mmm and explant cells was abolished by the pre-incubation of the pathogen with bovine anti-Mmm immune sera. Mmm was able to survive and proliferate in all tracheal, bronchial and lung explants, during the entire time course of the experiments. LSCM and gentamicin invasion assay both confirmed that Mmm can enter non-phagocytic host cells. Taken together, our data supports bovine respiratory explants as a promising tool to investigate CBPP, alternative to cattle experimental infection.

  13. Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

    Directory of Open Access Journals (Sweden)

    Nava Pat

    2011-03-01

    Full Text Available Abstract Background Is Impulse Oscillometry System (IOS a valuable tool to measure respiratory system function in Children? Asthma (A is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation. IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC and augmented RIC (aRIC models have emerged, which offer advantages over earlier models. Methods IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B and post- bronchodilation (post-B conditions over a period of 2 years. Results and Discussion Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress? Children were classified into two main categories: Healthy (H and Small Airway-Impaired (SAI. The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children. The two model parameters: peripheral compliance (Cp and peripheral resistance (Rp tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle" showed good correlations. Conclusions What are the most useful IOS and model parameters? In

  14. The new ICRP respiratory model for radiation protection (ICRP 66) : applications and comparative evaluations

    International Nuclear Information System (INIS)

    Castellani, C.M.; Luciani, A.

    1996-02-01

    The aim of this report is to present the New ICRP Respiratory Model Tract for Radiological Protection. The model allows considering anatomical and physiological characteristics, giving reference values for children aged 3 months, 1, 5,10, and 15 years for adults; it also takes into account aerosol and gas characteristics. After a general description of the model structure, deposition, clearance and dosimetric models are presented. To compare the new and previous model (ICRP 30), dose coefficients (committed effective dose for unit intake) foe inhalation of radionuclides by workers are calculated considering aerosol granulometries with activity median aerodynamic of 1 and 5 μm, reference values for the respective publications. Dose coefficients and annual limits of intakes concerning respective dose limits (50 and 20 mSv respectively for ICRP 26 and 60) for workers and for members of population in case of dispersion of fission products aerosols, are finally calculated

  15. Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, D.A.; Nikula, K.J.; Avila, K. [and others

    1995-12-01

    The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models to human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.

  16. Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

    Science.gov (United States)

    Yanagi, S; Ashitani, J; Imai, K; Kyoraku, Y; Sano, A; Matsumoto, N; Nakazato, M

    2007-01-01

    Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

  17. Identification of common biological pathways and drug targets across multiple respiratory viruses based on human host gene expression analysis.

    Directory of Open Access Journals (Sweden)

    Steven B Smith

    Full Text Available Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning.In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease.Our study suggests that

  18. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...... studies have considered data sets with just one behavioral variable such as email communication. The Social Fabric interdisciplinary research project is an attempt to collect a more complete data set on human behavior by providing 1000 smartphones with pre-installed data collection software to students...... data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived...

  19. Frequency of human bocavirus (HBoV) infection among children with febrile respiratory symptoms in Argentina, Nicaragua and Peru

    Science.gov (United States)

    Salmón‐Mulanovich, Gabriela; Sovero, Merly; Laguna‐Torres, V. Alberto; Kochel, Tadeusz J.; Lescano, Andres G.; Chauca, Gloria; Sanchez, J. Felix; Rodriguez, Francisco; Parrales, Eduardo; Ocaña, Victor; Barrantes, Melvin; Blazes, David L.; Montgomery, Joel M.

    2010-01-01

    Please cite this paper as: Salmón‐Mulanovich et al. (2010) Frequency of human bocavirus (HBoV) infection among children with febrile respiratory symptoms in Argentina, Nicaragua and Peru. Influenza and Other Respiratory Viruses 5(1), 1–5. Background  Globally, respiratory infections are the primary cause of illness in developing countries, specifically among children; however, an etiological agent for many of these illnesses is rarely identified. Objectives  Our study aimed to estimate the frequency of human bocavirus (HBoV) infection among pediatric populations in Argentina, Nicaragua and Peru. Methods  We conducted a cross‐sectional study using stored samples of an influenza‐like illness surveillance program. Irrespective of previous diagnosis, nasopharyngeal or nasal swab specimens were randomly selected and tested using real‐time PCR from three sites during 2007 from patients younger than 6 years old. Results  A total of 568 specimens from Argentina (185), Nicaragua (192) and Peru (191) were tested. The prevalence of HBoV was 10·8% (95% CI: 6·3; 15·3) in Argentina, 33·3% in Nicaragua (95% CI: 26·6; 40·1) and 25·1% in Peru (95% CI: 18·9; 31·3). Conclusions  These findings demonstrate circulation of HBoV in Argentina, Nicaragua and Peru among children with influenza‐like symptoms enrolled in a sentinel surveillance program. PMID:21138534

  20. Simulation of The ICRP-30 Dosimetric Model for the Respiratory Tract

    International Nuclear Information System (INIS)

    Giaddui, T.; Atia, M. A.

    2004-01-01

    Matlab was used to write a simulation program (ACID1) to simulate the ICRP-30 dosimetric model for the respiratory tract. The program (a new version of the one presented at the sixth Arab conference held in Cairo 2002) calculates a series of dosimetric quantities for the reference man as a result of the inhalation of any radionuclide. The program also plots the variation of activity with time for all organs and provided with a graphical user interface to make it friendly user. The results obtained by this program was compared with similar results obtained by other source and found to be very close. (Authors)

  1. Respiratory compensation in projection imaging using a magnification and displacement model

    International Nuclear Information System (INIS)

    Crawford, C.R.; King, K.F.; Ritchie, C.J.; Godwin, J.D.

    1996-01-01

    Respiratory motion during the collection of computed tomography (CT) projections generates structured artifacts and a loss of resolution that can render the scans unusable. This motion is problematic in scans of those patients who cannot suspend respiration, such as the very young or incubated patients. In this paper, the authors present an algorithm that can be used to reduce motion artifacts in CT scans caused by respiration. An approximate model for the effect of respiration is that the object cross section under interrogation experiences time-varying magnification and displacement along two axes. Using this model an exact filtered backprojection algorithm is derived for the case of parallel projections. The result is extended to generate an approximate reconstruction formula for fan-beam projections. Computer simulations and scans of phantoms on a commercial CT scanner validate the new reconstruction algorithms for parallel and fan-beam projections. Significant reduction in respiratory artifacts is demonstrated clinically when the motion model is satisfied. The method can be applied to projection data used in CT single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI)

  2. Human Modeling For Ground Processing Human Factors Engineering Analysis

    Science.gov (United States)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over that last few years using human modeling for human factors engineering analysis for design of spacecraft and launch vehicles. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the different types of human modeling used currently and in the past at Kennedy Space Center (KSC) currently, and to explain the future plans for human modeling for future spacecraft designs.

  3. Cardio-respiratory development in bird embryos: new insights from a venerable animal model

    Directory of Open Access Journals (Sweden)

    Warren W. Burggren

    Full Text Available ABSTRACT The avian embryo is a time-honored animal model for understanding vertebrate development. A key area of extensive study using bird embryos centers on developmental phenotypic plasticity of the cardio-respiratory system and how its normal development can be affected by abiotic factors such as temperature and oxygen availability. Through the investigation of the plasticity of development, we gain a better understanding of both the regulation of the developmental process and the embryo's capacity for self-repair. Additionally, experiments with abiotic and biotic stressors during development have helped delineate not just critical windows for avian cardio-respiratory development, but the general characteristics (e.g., timing and dose-dependence of critical windows in all developing vertebrates. Avian embryos are useful in exploring fetal programming, in which early developmental experiences have implications (usually negative later in life. The ability to experimentally manipulate the avian embryo without the interference of maternal behavior or physiology makes it particularly useful in future studies of fetal programming. The bird embryo is also a key participant in studies of transgenerational epigenetics, whether by egg provisioning or effects on the germline that are transmitted to the F1 generation (or beyond. Finally, the avian embryo is heavily exploited in toxicology, in which both toxicological testing of potential consumer products as well as the consequences of exposure to anthropogenic pollutants are routinely carried out in the avian embryo. The avian embryo thus proves useful on numerous experimental fronts as an animal model that is concurrently both of adequate complexity and sufficient simplicity for probing vertebrate cardio-respiratory development.

  4. A Simulink model for the human circulatory system.

    Science.gov (United States)

    Wabel, P; Leonhardt, S

    1998-01-01

    This paper presents the mathematical simulation of the human circulatory system. The model is based on the former work of Coleman and co-workers and has been redesigned for simulation with the Matlab toolbox "Simulink". It includes the heart and the peripheral circulation, the respiratory system, the kidneys and the major neural and hormonal control mechanisms, which are necessary for maintaining homeostasis. The model contains more than 30 blocks with over 200 physiological variables, which can be accessed and plotted during the simulation.

  5. Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.

    Science.gov (United States)

    Munday, Diane C; Howell, Gareth; Barr, John N; Hiscox, Julian A

    2015-03-01

    The aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (HRSV), a major cause of paediatric illness. Quantitative proteomics, underpinned by stable isotope labelling with amino acids in cell culture, coupled to LC-MS/MS, was applied to mitochondrial fractions prepared from HRSV-infected and mock-infected cells 12 and 24 h post-infection. Datasets were analysed using ingenuity pathway analysis, and the results were validated and characterised using bioimaging, targeted inhibition and gene depletion. The data quantitatively indicated that antiviral signalling proteins converged on mitochondria during HRSV infection. The mitochondrial receptor protein Tom70 was found to act in an antiviral manner, while its chaperone, Hsp90, was confirmed to be a positive viral factor. Proteins associated with different organelles were also co-enriched in the mitochondrial fractions from HRSV-infected cells, suggesting that alterations in organelle dynamics and membrane associations occur during virus infection. Protein and pathway-specific alterations occur to the mitochondrial proteome in a spatial and temporal manner during HRSV infection, suggesting that this organelle may have altered functions. These could be targeted as part of potential therapeutic strategies to disrupt virus biology. © 2014 Royal Pharmaceutical Society.

  6. The effects of human serum to the morphology, proliferation and gene expression level of the respiratory epithelium in vitro.

    Science.gov (United States)

    Yunus, Mohd Heikal Mohd; Siang, Kan Chan; Hashim, Nurul Izzati; Zhi, Ng Pei; Zamani, Nur Fathurah; Sabri, Primuharsa Putra; Busra, Mohd Fauzi; Chowdhury, Shiplu Roy; Idrus, Ruszymah Binti Haji

    2014-08-01

    The culture of human airway epithelial cells has played an important role in advancing our understanding of the metabolic and molecular mechanisms underlying normal function and disease pathology of airway epithelial cells. The present study focused on investigating the effects of human serum (HS) on the qualitative and quantitative properties of the human respiratory epithelium compared to the fetal bovine serum (FBS), as a supplement in culture. Respiratory epithelial (RE) cells derived from human nasal turbinate were co-cultured with fibroblasts, subsequently separated at 80-90% confluency by differential trypsinization. RE cells were then sub-cultured into 2 different plates containing 5% allogenic HS and FBS supplemented media respectively up to passage 1 (P1). Cell morphology, growth rate, cell viability and population doubling time were assessed under light microscope, and levels of gene expression were measured via real time reverse transcriptase-polymerase chain reaction (qRT-PCR). RE cells appeared as polygonal shape and expanded when cultured in HS whereas RE cells in FBS were observed to be easily matured thus limit the RE cells expansion. Proliferation rate of RE cells in HS supplemented media (7673.18 ± 1207.15) was 3 times higher compared to RE in FBS supplemented media (2357.68 ± 186.85). Furthermore, RE cells cultured in HS-supplemented media required fewer days (9.15 ± 1.10) to double in numbers compared to cells cultured in FBS-supplemented media (13.66 ± 0.81). Both the differences were significant (p0.05). In conclusion, HS is a comparatively better choice of media supplement in accelerating growth kinetics of RE cells in vitro thus producing a better quality of respiratory epithelium for future tracheal reconstruction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Flexible Bayesian Human Fecundity Models.

    Science.gov (United States)

    Kim, Sungduk; Sundaram, Rajeshwari; Buck Louis, Germaine M; Pyper, Cecilia

    2012-12-01

    Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis.

  8. Modelling biased human trust dynamics

    NARCIS (Netherlands)

    Hoogendoorn, M.; Jaffry, S.W.; Maanen, P.P. van; Treur, J.

    2013-01-01

    Abstract. Within human trust related behaviour, according to the literature from the domains of Psychology and Social Sciences often non-rational behaviour can be observed. Current trust models that have been developed typically do not incorporate non-rational elements in the trust formation

  9. Human Resource Models: An Overview.

    Science.gov (United States)

    1982-11-01

    simulation models in which human performance plays an important part see, A.I. Siegel and J.J. Wolf , "Digital Behavioral Simulation--State-of-the-Art...atford and Petersen, Charles C., ’Mfaritine 421-439 Factors Adfecting Iberian Security," (Factores hbritimos Que "Northwestern University, Evanston

  10. Changes in respiratory activity induced by mastication during oral breathing in humans.

    Science.gov (United States)

    Daimon, Shigeru; Yamaguchi, Kazunori

    2014-06-01

    We examined the effect of oral breathing on respiratory movements, including the number of respirations and the movement of the thoracic wall at rest and while chewing gum. Forty normal nose breathers were selected by detecting expiratory airflow from the mouth using a CO2 sensor. Chest measurements were recorded using a Piezo respiratory belt transducer, and electromyographic (EMG) activity of the masseter and trapezius muscles were recorded at rest and while chewing gum during nasal or oral breathing. Oral breathing was introduced by completely occluding the nostrils with a nose clip. During oral breathing, the respiration rate was significantly lower while chewing gum than while at rest (P oral breathing than during nasal breathing (P oral breathing, thoracic movement was significantly higher while chewing gum than while at rest (P oral breathing than during nasal breathing (P oral breathing. The activity of the trapezius muscle coincided with increased movement of the thoracic wall. Chewing food while breathing through the mouth interferes with and decreases the respiratory cycle and promotes unusual respiratory movement of the thoracic wall, which is directed by the activity of accessory muscles of respiration. Copyright © 2014 the American Physiological Society.

  11. Experimentally determined human respiratory tract deposition of airborne particles at a busy street

    DEFF Research Database (Denmark)

    Löndahl, Jakob; Massling, Andreas; Swietlicki, Erik

    2009-01-01

    was measured with a novel setup in 9 healthy subjects breathing by mouth on the windward side of a busy street in Copenhagen, Denmark. The aerosol was characterized both at the curbside and, to obtain the background concentration, at rooftop level. Particle hygroscopicity, a key parameter affecting respiratory...

  12. Animal models for human diseases.

    Science.gov (United States)

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  13. Respiratory Health – Exposure Measurements and Modeling in the Fragrance and Flavour Industry

    Science.gov (United States)

    Angelini, Eric; Camerini, Gerard; Diop, Malick; Roche, Patrice; Rodi, Thomas; Schippa, Christine; Thomas, Thierry

    2016-01-01

    Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH) identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring), 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to various exposure

  14. Respiratory Health - Exposure Measurements and Modeling in the Fragrance and Flavour Industry.

    Directory of Open Access Journals (Sweden)

    Eric Angelini

    Full Text Available Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring, 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to

  15. Reversion of somatic mutations of the respiratory syncytial virus-specific human monoclonal antibody Fab19 reveal a direct relationship between association rate and neutralizing potency.

    Science.gov (United States)

    Bates, John T; Keefer, Christopher J; Utley, Thomas J; Correia, Bruno E; Schief, William R; Crowe, James E

    2013-04-01

    The role of affinity in determining neutralizing potency of mAbs directed against viruses is not well understood. We investigated the kinetic, structural, and functional advantage conferred by individual naturally occurring somatic mutations in the Ab H chain V region of Fab19, a well-described neutralizing human mAb directed to respiratory syncytial virus. Comparison of the affinity-matured Ab Fab19 with recombinant Fab19 Abs that were variants containing reverted amino acids from the inferred unmutated ancestor sequence revealed the molecular basis for affinity maturation of this Ab. Enhanced binding was achieved through mutations in the third H chain CDR (HCDR3) that conferred a markedly faster on-rate and a desirable increase in antiviral neutralizing activity. In contrast, most somatic mutations in the HCDR1 and HCDR2 regions did not significantly enhance Ag binding or antiviral activity. We observed a direct relationship between the measured association rate (Kon) for F protein and antiviral activity. Modeling studies of the structure of the Ag-Ab complex suggested the HCDR3 loop interacts with the antigenic site A surface loop of the respiratory syncytial virus F protein, previously shown to contain the epitope for this Ab by experimentation. These studies define a direct relationship of affinity and neutralizing activity for a viral glycoprotein-specific human mAb.

  16. Replication and clearance of respiratory syncytial virus - Apoptosis is an important pathway of virus clearance after experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Viuff, B.; Tjørnehøj, Kirsten; Larsen, Lars Erik

    2002-01-01

    and the infections with human respiratory syncytial. virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication...... and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared...

  17. Comparisons of calculated respiratory tract deposition of particles based on the NCRP/ITRI model and the new ICRP66 model

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Hsu-Chi; Phalen, R.F. [Univ. of California, Irvine, CA (United States); Chang, I. [Lovelace Inst., Albuquerque, NM (United States)] [and others

    1995-12-01

    The National Council on Radiation Protection and Measurements (NCRP) in the United States and the International Commission on Radiological Protection (ICRP) have been independently reviewing and revising respiratory tract dosimetry models for inhaled radioactive aerosols. The newly proposed NCRP respiratory tract dosimetry model represents a significant change in philosophy from the old ICRP Task Group model. The proposed NCRP model describes respiratory tract deposition, clearance, and dosimetry for radioactive substances inhaled by workers and the general public and is expected to be published soon. In support of the NCRP proposed model, ITRI staff members have been developing computer software. Although this software is still incomplete, the deposition portion has been completed and can be used to calculate inhaled particle deposition within the respiratory tract for particle sizes as small as radon and radon progeny ({approximately} 1 nm) to particles larger than 100 {mu}m. Recently, ICRP published their new dosimetric model for the respiratory tract, ICRP66. Based on ICRP66, the National Radiological Protection Board of the UK developed PC-based software, LUDEP, for calculating particle deposition and internal doses. The purpose of this report is to compare the calculated respiratory tract deposition of particles using the NCRP/ITRI model and the ICRP66 model, under the same particle size distribution and breathing conditions. In summary, the general trends of the deposition curves for the two models were similar.

  18. Reassessment of the cardio-respiratory stress response, using the king penguin as a model.

    Science.gov (United States)

    Willener, Astrid S T; Halsey, Lewis G; Strike, Siobhán; Enstipp, Manfred R; Georges, Jean-Yves; Handrich, Yves

    2015-01-01

    Research in to short-term cardio-respiratory changes in animals in reaction to a psychological stressor typically describes increases in rate of oxygen consumption (V̇(O2)) and heart rate. Consequently, the broad consensus is that they represent a fundamental stressor response generalizable across adult species. However, movement levels can also change in the presence of a stressor, yet studies have not accounted for this possible confound on heart rate. Thus the direct effects of psychological stressors on the cardio-respiratory system are not resolved. We used an innovative experimental design employing accelerometers attached to king penguins (Aptenodytes patagonicus) to measure and thus account for movement levels in a sedentary yet free-to-move animal model during a repeated measures stress experiment. As with previous studies on other species, incubating king penguins (N = 6) exhibited significant increases in both V̇(O2) and heart rate when exposed to the stressor. However, movement levels, while still low, also increased in response to the stressor. Once this was accounted for by comparing periods of time during the control and stress conditions when movement levels were similar as recorded by the accelerometers, only V̇(O2) significantly increased; there was no change in heart rate. These findings offer evidence that changing movement levels have an important effect on the measured stress response and that the cardio-respiratory response per se to a psychological stressor (i.e. the response as a result of physiological changes directly attributable to the stressor) is an increase in V̇(O2) without an increase in heart rate.

  19. Effect of environmental exposure to hydrogen sulfide on central nervous system and respiratory function: a systematic review of human studies.

    Science.gov (United States)

    Lim, Eunjung; Mbowe, Omar; Lee, Angela S W; Davis, James

    2016-01-01

    Assessment of the health effects of low-level exposure to hydrogen sulfide (H2S) on humans through experiments, industrial, and community studies has shown inconsistent results. To critically appraise available studies investigating the effect of H2S on the central nervous system (CNS) and on respiratory function. A search was conducted in 16 databases for articles published between January 1980 and July 2014. Two researchers independently evaluated potentially relevant papers based on a set of inclusion/exclusion criteria. Twenty-seven articles met the inclusion criteria: 6 experimental, 12 industry-based studies, and 10 community-based studies (one article included both experimental and industry-based studies). The results of the systematic review varied by study setting and quality. Several community-based studies reported associations between day-to-day variations in H2S levels and health outcomes among patients with chronic respiratory conditions. However, evidence from the largest and better-designed community-based studies did not support that chronic, ambient H2S exposure has health effects on the CNS or respiratory function. Results from industry-based studies varied, reflecting the diversity of settings and the broad range of H2S exposures. Most studies did not have individual measurements of H2S exposure. The results across studies were inconsistent, justifying the need for further research.

  20. Non-typeable Haemophilus influenzae protects human airway epithelial cells from a subsequent respiratory syncytial virus challenge.

    Science.gov (United States)

    Hartwig, Stacey M; Ketterer, Margaret; Apicella, Michael A; Varga, Steven M

    2016-11-01

    Respiratory syncytial virus (RSV) and the common commensal and opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) both serve as a frequent cause of respiratory infection in children. Although it is well established that some respiratory viruses can increase host susceptibility to secondary bacterial infections, few studies have examined how commensal bacteria could influence a secondary viral response. Here, we examined the impact of NTHi exposure on a subsequent RSV infection of human bronchial epithelial cells (16HBE14o-). Co-culture of 16HBE14o- cells with NTHi resulted in inhibition of viral gene expression following RSV infection. 16HBE14o- cells co-cultured with heat-killed NTHi failed to protect against an RSV infection, indicating that protection requires live bacteria. However, NTHi did not inhibit influenza A virus replication, indicating that NTHi-mediated protection was RSV-specific. Our data demonstrates that prior exposure to a commensal bacterium such as NTHi can elicit protection against a subsequent RSV infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Reduction of irregular breathing artifacts in respiration-correlated CT images using a respiratory motion model.

    Science.gov (United States)

    Hertanto, Agung; Zhang, Qinghui; Hu, Yu-Chi; Dzyubak, Oleksandr; Rimner, Andreas; Mageras, Gig S

    2012-06-01

    Respiration-correlated CT (RCCT) images produced with commonly used phase-based sorting of CT slices often exhibit discontinuity artifacts between CT slices, caused by cycle-to-cycle amplitude variations in respiration. Sorting based on the displacement of the respiratory signal yields slices at more consistent respiratory motion states and hence reduces artifacts, but missing image data (gaps) may occur. The authors report on the application of a respiratory motion model to produce an RCCT image set with reduced artifacts and without missing data. Input data consist of CT slices from a cine CT scan acquired while recording respiration by monitoring abdominal displacement. The model-based generation of RCCT images consists of four processing steps: (1) displacement-based sorting of CT slices to form volume images at 10 motion states over the cycle; (2) selection of a reference image without gaps and deformable registration between the reference image and each of the remaining images; (3) generation of the motion model by applying a principal component analysis to establish a relationship between displacement field and respiration signal at each motion state; (4) application of the motion model to deform the reference image into images at the 9 other motion states. Deformable image registration uses a modified fast free-form algorithm that excludes zero-intensity voxels, caused by missing data, from the image similarity term in the minimization function. In each iteration of the minimization, the displacement field in the gap regions is linearly interpolated from nearest neighbor nonzero intensity slices. Evaluation of the model-based RCCT examines three types of image sets: cine scans of a physical phantom programmed to move according to a patient respiratory signal, NURBS-based cardiac torso (NCAT) software phantom, and patient thoracic scans. Comparison in physical motion phantom shows that object distortion caused by variable motion amplitude in phase

  2. Replication of avian, human and swine influenza viruses in porcine respiratory explants and association with sialic acid distribution

    Directory of Open Access Journals (Sweden)

    Nauwynck Hans J

    2010-02-01

    Full Text Available Abstract Background Throughout the history of human influenza pandemics, pigs have been considered the most likely "mixing vessel" for reassortment between human and avian influenza viruses (AIVs. However, the replication efficiencies of influenza viruses from various hosts, as well as the expression of sialic acid (Sia receptor variants in the entire porcine respiratory tract have never been studied in detail. Therefore, we established porcine nasal, tracheal, bronchial and lung explants, which cover the entire porcine respiratory tract with maximal similarity to the in vivo situation. Subsequently, we assessed virus yields of three porcine, two human and six AIVs in these explants. Since our results on virus replication were in disagreement with the previously reported presence of putative avian virus receptors in the trachea, we additionally studied the distribution of sialic acid receptors by means of lectin histochemistry. Human (Siaα2-6Gal and avian virus receptors (Siaα2-3Gal were identified with Sambucus Nigra and Maackia amurensis lectins respectively. Results Compared to swine and human influenza viruses, replication of the AIVs was limited in all cultures but most strikingly in nasal and tracheal explants. Results of virus titrations were confirmed by quantification of infected cells using immunohistochemistry. By lectin histochemistry we found moderate to abundant expression of the human-like virus receptors in all explant systems but minimal binding of the lectins that identify avian-like receptors, especially in the nasal, tracheal and bronchial epithelium. Conclusions The species barrier that restricts the transmission of influenza viruses from one host to another remains preserved in our porcine respiratory explants. Therefore this system offers a valuable alternative to study virus and/or host properties required for adaptation or reassortment of influenza viruses. Our results indicate that, based on the expression of Sia

  3. Flipped classroom model improves graduate student performance in cardiovascular, respiratory, and renal physiology.

    Science.gov (United States)

    Tune, Johnathan D; Sturek, Michael; Basile, David P

    2013-12-01

    The purpose of this study was to assess the effectiveness of a traditional lecture-based curriculum versus a modified "flipped classroom" curriculum of cardiovascular, respiratory, and renal physiology delivered to first-year graduate students. Students in both courses were provided the same notes and recorded lectures. Students in the modified flipped classroom were required to watch the prerecorded lectures before class and then attend class, where they received a quiz or homework covering material in each lecture (valued at 25% of the final grade) followed by a question and answer/problem-solving period. In the traditional curriculum, attending lectures was optional and there were no quizzes. Evaluation of effectiveness and student performance was achieved by having students in both courses take the same multiple-choice exams. Within a comparable group of graduate students, participants in the flipped course scored significantly higher (P ≤ 0.05) on the cardiovascular, respiratory, and weighted cumulative sections by an average of >12 percentage points. Exam averages for students in the flipped course also tended to be higher on the renal section by ∼11 percentage points (P = 0.06). Based on our experience and responses obtained in blinded student surveys, we propose that the use of homework and in-class quizzes were critical motivating factors that likely contributed to the increase in student exam performance. Taken together, our findings support that the flipped classroom model is a highly effective means in which to disseminate key physiological concepts to graduate students.

  4. The Evaluation of a Pulmonary Display to Detect Adverse Respiratory Events Using High Resolution Human Simulator

    Science.gov (United States)

    Wachter, S. Blake; Johnson, Ken; Albert, Robert; Syroid, Noah; Drews, Frank; Westenskow, Dwayne

    2006-01-01

    Objective Authors developed a picture-graphics display for pulmonary function to present typical respiratory data used in perioperative and intensive care environments. The display utilizes color, shape and emergent alerting to highlight abnormal pulmonary physiology. The display serves as an adjunct to traditional operating room displays and monitors. Design To evaluate the prototype, nineteen clinician volunteers each managed four adverse respiratory events and one normal event using a high-resolution patient simulator which included the new displays (intervention subjects) and traditional displays (control subjects). Between-group comparisons included (i) time to diagnosis and treatment for each adverse respiratory event; (ii) the number of unnecessary treatments during the normal scenario; and (iii) self-reported workload estimates while managing study events. Measurements Two expert anesthesiologists reviewed video-taped transcriptions of the volunteers to determine time to treat and time to diagnosis. Time values were then compared between groups using a Mann-Whitney-U Test. Estimated workload for both groups was assessed using the NASA-TLX and compared between groups using an ANOVA. P-values < 0.05 were considered significant. Results Clinician volunteers detected and treated obstructed endotracheal tubes and intrinsic PEEP problems faster with graphical rather than conventional displays (p < 0.05). During the normal scenario simulation, 3 clinicians using the graphical display, and 5 clinicians using the conventional display gave unnecessary treatments. Clinician-volunteers reported significantly lower subjective workloads using the graphical display for the obstructed endotracheal tube scenario (p < 0.001) and the intrinsic PEEP scenario (p < 0.03). Conclusion Authors conclude that the graphical pulmonary display may serve as a useful adjunct to traditional displays in identifying adverse respiratory events. PMID:16929038

  5. Haemophilus haemolyticus: A Human Respiratory Tract Commensal to Be Distinguished from Haemophilus influenzae

    DEFF Research Database (Denmark)

    Murphy, T.F.; Brauer, A.L.; Sethi, S.

    2007-01-01

    Background. Haemophilus influenzae is a common pathogen in adults with chronic obstructive pulmonary disease (COPD). In a prospective study, selected isolates of apparent H. influenzae had an altered phenotype. We tested the hypothesis that these variant strains were genetically different from ty...... distinguish H. haemolyticus from H. influenzae. H. haemolyticus is a respiratory tract commensal. The recognition that some strains of apparent H. influenzae are H. haemolyticus substantially strengthens the association of true H. influenzae with clinical infection....

  6. Within-breath arterial PO2 oscillations in an experimental model of acute respiratory distress syndrome.

    Science.gov (United States)

    Williams, E M; Viale, J P; Hamilton, R M; McPeak, H; Sutton, L; Hahn, C E

    2000-09-01

    Tidal ventilation causes within-breath oscillations in alveolar oxygen concentration, with an amplitude which depends on the prevailing ventilator settings. These alveolar oxygen oscillations are transmitted to arterial oxygen tension, PaO2, but with an amplitude which now depends upon the magnitude of venous admixture or true shunt, QS/QT. We investigated the effect of positive end-expiratory pressure (PEEP) on the amplitude of the PaO2 oscillations, using an atelectasis model of shunt. Blood PaO2 was measured on-line with an intravascular PaO2 sensor, which had a 2-4 s response time (10-90%). The magnitude of the time-varying PaO2 oscillation was titrated against applied PEEP while tidal volume, respiratory rate and inspired oxygen concentration were kept constant. The amplitude of the PaO2 oscillation, delta PaO2, and the mean PaO2 value varied with the level of PEEP applied. At zero PEEP, both the amplitude and the mean were at their lowest values. As PEEP was increased to 1.5 kPa, both delta PaO2 and the mean PaO2 increased to a maximum. Thereafter, the mean PaO2 increased but delta PaO2 decreased. Clear oscillations of PaO2 were seen even at the lowest mean PaO2, 9.5 kPa. Conventional respiratory models of venous admixture predict that these PaO2 oscillations will be reduced by the steep part of the oxyhaemoglobin dissociation curve if a constant pulmonary shunt exists throughout the whole respiratory cycle. The facts that the PaO2 oscillations occurred at all mean PaO2 values and that their amplitude increased with increasing PEEP suggest that QS/QT, in the atelectasis model, varies between end-expiration and end-inspiration, having a much lower value during inspiration than during expiration.

  7. Model-based setting of inspiratory pressure and respiratory rate in pressure-controlled ventilation

    International Nuclear Information System (INIS)

    Schranz, C; Möller, K; Becher, T; Schädler, D; Weiler, N

    2014-01-01

    Mechanical ventilation carries the risk of ventilator-induced-lung-injury (VILI). To minimize the risk of VILI, ventilator settings should be adapted to the individual patient properties. Mathematical models of respiratory mechanics are able to capture the individual physiological condition and can be used to derive personalized ventilator settings. This paper presents model-based calculations of inspiration pressure (p I ), inspiration and expiration time (t I , t E ) in pressure-controlled ventilation (PCV) and a retrospective evaluation of its results in a group of mechanically ventilated patients. Incorporating the identified first order model of respiratory mechanics in the basic equation of alveolar ventilation yielded a nonlinear relation between ventilation parameters during PCV. Given this patient-specific relation, optimized settings in terms of minimal p I and adequate t E can be obtained. We then retrospectively analyzed data from 16 ICU patients with mixed pathologies, whose ventilation had been previously optimized by ICU physicians with the goal of minimization of inspiration pressure, and compared the algorithm's ‘optimized’ settings to the settings that had been chosen by the physicians. The presented algorithm visualizes the patient-specific relations between inspiration pressure and inspiration time. The algorithm's calculated results highly correlate to the physician's ventilation settings with r = 0.975 for the inspiration pressure, and r = 0.902 for the inspiration time. The nonlinear patient-specific relations of ventilation parameters become transparent and support the determination of individualized ventilator settings according to therapeutic goals. Thus, the algorithm is feasible for a variety of ventilated ICU patients and has the potential of improving lung-protective ventilation by minimizing inspiratory pressures and by helping to avoid the build-up of clinically significant intrinsic positive end

  8. Online model checking for monitoring surrogate-based respiratory motion tracking in radiation therapy.

    Science.gov (United States)

    Antoni, Sven-Thomas; Rinast, Jonas; Ma, Xintao; Schupp, Sibylle; Schlaefer, Alexander

    2016-11-01

    Correlation between internal and external motion is critical for respiratory motion compensation in radiosurgery. Artifacts like coughing, sneezing or yawning or changes in the breathing pattern can lead to misalignment between beam and tumor and need to be detected to interrupt the treatment. We propose online model checking (OMC), a model-based verification approach from the field of formal methods, to verify that the breathing motion is regular and the correlation holds. We demonstrate that OMC may be more suitable for artifact detection than the prediction error. We established a sinusoidal model to apply OMC to the verification of respiratory motion. The method was parameterized to detect deviations from typical breathing motion. We analyzed the performance on synthetic data and on clinical episodes showing large correlation error. In comparison, we considered the prediction error of different state-of-the-art methods based on least mean squares (LMS; normalized LMS, nLMS; wavelet-based multiscale autoregression, wLMS), recursive least squares (RLSpred) and support vector regression (SVRpred). On synthetic data, OMC outperformed wLMS by at least 30 % and SVRpred by at least 141 %, detecting 70 % of transitions. No artifacts were detected by nLMS and RLSpred. On patient data, OMC detected 23-49 % of the episodes correctly, outperforming nLMS, wLMS, RLSpred and SVRpred by up to 544, 491, 408 and 258 %, respectively. On selected episodes, OMC detected up to 94 % of all events. OMC is able to detect changes in breathing as well as artifacts which previously would have gone undetected, outperforming prediction error-based detection. Synthetic data analysis supports the assumption that prediction is very insensitive to specific changes in breathing. We suggest using OMC as an additional safety measure ensuring reliable and fast stopping of irradiation.

  9. Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Mukae Hiroshi

    2005-11-01

    Full Text Available Abstract Background Human β-defensin-4 (hBD-4, a new member of the β-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF. Methods The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA. Localization of hBD-4 was studied through immunohistochemical analysis (IHC. We investigated the effects of lipopolysaccharide (LPS on hBD-4 expression and its release from small airway epithelial cells (SAEC. We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA. Results hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level. Conclusion This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.

  10. Zebrafish models for human cancer.

    Science.gov (United States)

    Shive, H R

    2013-05-01

    For decades, the advancement of cancer research has relied on in vivo models for examining key processes in cancer pathogenesis, including neoplastic transformation, progression, and response to therapy. These studies, which have traditionally relied on rodent models, have engendered a vast body of scientific literature. Recently, experimental cancer researchers have embraced many new and alternative model systems, including the zebrafish (Danio rerio). The general benefits of the zebrafish model for laboratory investigation, such as cost, size, fecundity, and generation time, were quickly superseded by the discovery that zebrafish are amenable to a wide range of investigative techniques, many of which are difficult or impossible to perform in mammalian models. These advantages, coupled with the finding that many aspects of carcinogenesis are conserved in zebrafish as compared with humans, have firmly established a unique niche for the zebrafish model in comparative cancer research. This article introduces methods for generating cancer models in zebrafish and reviews a range of models that have been developed for specific cancer types.

  11. Coupled and reduced dimensional modeling of respiratory mechanics during spontaneous breathing.

    Science.gov (United States)

    Ismail, M; Comerford, A; Wall, W A

    2013-11-01

    In this paper, we develop a total lung model based on a tree of 0D airway and acinar models for studying respiratory mechanics during spontaneous breathing. This model utilizes both computer tomography-based geometries and artificially generated lobe-filling airway trees to model the entire conducting region of the lung. Beyond the conducting airways, we develop an acinar model, which takes into account the alveolar tissue resistance, compliance, and the intrapleural pressure. With this methodology, we compare four different 0D models of airway mechanics and determine the best model based on a comparison with a 3D-0D coupled model of the conducting airways; this methodology is possible because the majority of airway resistance is confined to the lower generations, that is, the trachea and the first few bronchial generations. As an example application of the model, we simulate the flow and pressure dynamics under spontaneous breathing conditions, that is, at flow conditions driven purely by pleural space pressure. The results show good agreement, both qualitatively and quantitatively, with reported physiological values. One of the key advantages of this model is the ability to provide insight into lung ventilation in the peripheral regions. This is often crucial because this is where information, specifically for studying diseases and gas exchange, is needed. Thus, the model can be used as a tool for better understanding local peripheral lung mechanics without excluding the upper portions of the lung. This tool will be also useful for in vitro investigations of lung mechanics in both health and disease. Copyright © 2013 John Wiley & Sons, Ltd.

  12. beta. -Endorphin and related peptides suppress phorbol myristate acetate-induced respiratory burst in human polymorphonuclear leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Diamant, M.; Henricks, P.A.J.; Nijkamp, F.P.; de Wied, D. (Univ. of Utrecht (Netherlands))

    1989-01-01

    In the present study, the immunomodulatory effect of {beta}-endorphin ({beta}-E) and shorter pro-opiomelancortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity and their non-opioid derivatives were tested. With the exception of {alpha}-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10{sup {minus}17}M and higher than 10{sup {minus}8}M were without effect. {beta}-E and dT{beta}E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations. {gamma}-E and dT{gamma}E proved to be less potent inhibitors, reaching maximal effect at higher concentrations. DE{gamma}E exerted an even less pronounced but still significant suppressive effect at the concentration of 10{sup {minus}10}M. None of the endorphins tested was shown to affect resting oxidative metabolism in the PMN. The modulatory effects of the opioid peptides could not be blocked by the opioid antagonist naloxone.

  13. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Viviane F Botosso

    2009-01-01

    Full Text Available Human respiratory syncytial virus (HRSV is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  14. IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells

    Science.gov (United States)

    Laoukili, Jamila; Perret, Eric; Willems, Tom; Minty, Adrian; Parthoens, Eef; Houcine, Odile; Coste, Andre; Jorissen, Mark; Marano, Francelyne; Caput, Daniel; Tournier, Frédéric

    2001-01-01

    In animal models of asthma, interleukin-13 (IL-13) induces goblet cell metaplasia, eosinophil infiltration of the bronchial mucosa, and bronchial hyperreactivity, but the basis of its effects on airway epithelia remain unknown. Lesions of the epithelial barrier, frequently observed in asthma and other chronic lung inflammatory diseases, are repaired through proliferation, migration, and differentiation of epithelial cells. An inflammatory process may then, therefore, influence epithelial regeneration. We have thus investigated the effect of IL-13 on mucociliary differentiation of human nasal epithelial cells in primary culture. We show that IL-13 alters ciliated cell differentiation and increases the proportion of secretory cells. IL-13 downregulates the actin-binding protein ezrin and other cytoskeletal components. IL-13 also impairs lateral cell contacts and interferes with the apical localization of ezrin seen in differentiated ciliated cells. In addition, an IL-4 antagonistic mutant protein (Y124D), which binds to the IL-4 receptor α subunit, a common chain of IL-4 and IL-13 receptors, inhibits IL-13’s effects. IL-13 also decreases ciliary beat frequency in a time- and dose-dependent manner. These results suggest that, in human allergic asthmatic responses, IL-13 affects both ciliated and secretory cell differentiation, leading to airway damage and obstruction. PMID:11748265

  15. An optimized in vitro model of the respiratory tract wall to study particle cell interactions.

    Science.gov (United States)

    Blank, Fabian; Rothen-Rutishauser, Barbara M; Schurch, Samuel; Gehr, Peter

    2006-01-01

    As a part of the respiratory tissue barrier, lung epithelial cells play an important role against the penetration of the body by inhaled particulate foreign materials. In most cell culture models, which are designed to study particle-cell interactions, the cells are immersed in medium. This does not reflect the physiological condition of lung epithelial cells which are exposed to air, separated from it only by a very thin liquid lining layer with a surfactant film at the air-liquid interface. In this study, A549 epithelial cells were grown on microporous membranes in a two chamber system. After the formation of a confluent monolayer the cells were exposed to air. The morphology of the cells and the expression of tight junction proteins were studied with confocal laser scanning and transmission electron microscopy. Air-exposed cells maintained monolayer structure for 2 days, expressed tight junctions and developed transepithelial electrical resistance. Surfactant was produced and released at the apical side of the air-exposed epithelial cells. In order to study particle-cell interactions fluorescent 1 microm polystyrene particles were sprayed over the epithelial surface. After 4 h, 8.8% of particles were found inside the epithelium. This fraction increased to 38% after 24 h. During all observations, particles were always found in the cells but never between them. In this study, we present an in vitro model of the respiratory tract wall consisting of air-exposed lung epithelial cells covered by a liquid lining layer with a surfactant film to study particle-cell interactions.

  16. Clinical characterization of influenza A and human respiratory syncytial virus among patients with influenza like illness.

    Science.gov (United States)

    Saxena, Swati; Singh, Dharamveer; Zia, Amreen; Umrao, Jyoti; Srivastava, Naveen; Pandey, Ankita; Singh, Sushma; Bhattacharya, Piyali; Kumari, Reema; Kushwaha, Ramawadh; Dhole, T N

    2017-01-01

    Influenza A and Respiratory Syncytial Virus (RSV) has been recognized as a major cause of acute respiratory tract infection. H1N1 is one of the subtypes of influenza A, pandemic worldwide in July 2009, causing 18,449 deaths globally. To investigate the prevalence and clinical manifestation of the influenza A, H1N1pdm09, and RSV. Throat/nasal swab collected from the patients of all age group either outpatients/inpatients having respiratory illness from 2 to 5 days. The clinical data were recorded in a predesigned questionnaire. RNA was extracted and analyzed by real time PCR at a tertiary care center, 2009-2014. Total 4,352 samples tested for influenza A and H1N1. Out of 4,352, 32.2% (median positivity 21%; range 16-41% during 6 years) were positive for influenza A and 19% were H1N1 (median positivity 16.7%; range 8.7-23% during 6 years). Total 1653 samples were analyzed for RSV from 2011 to 2014, 12% were RSV positive (median positivity 11.35%; range 10-16.3% during 4 years). Pharyngitis, dyspnea were frequent symptoms in influenza A and H1N1 (P influenza A and H1N1 was higher in age-group 21-30, whereas RSV in infant and children. H1N1 and RSV were co-circulated and have common clinical symptoms particularly in lower age group. Therefore, laboratory confirmation is necessary for further disease prognosis. Age was an important risk factor that affects the positivity of influenza A, H1N1, and RSV. Different clinical manifestation of H1N1 and RSV will be helpful for early and accurate diagnosis. J. Med. Virol. 89:49-54, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak

    Directory of Open Access Journals (Sweden)

    Yuri Kim

    2016-03-01

    Full Text Available The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV causes a severe respiratory infection with a high mortality rate (~35%. MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%. Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD of viral spike (S protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.

  18. Counseling and Human Sexuality: A Training Model.

    Science.gov (United States)

    Fyfe, Bill

    1980-01-01

    Presents a counseling and human sexuality course model that provides counselors with an information base in human sexuality and assists them in exploring the emotional aspects of sexuality. Human sexuality is a vital aspect of personal development. (Author)

  19. Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fang (UMM)

    2008-09-23

    It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

  20. Potential risks to human respiratory health from "acid fog": evidence from experimental studies of volunteers.

    Science.gov (United States)

    Hackney, J D; Linn, W S; Avol, E L

    1985-11-01

    Observations of high acidity (pH as low as 1.7) in fogwater collected in polluted areas have provoked concern for public health. Effects of exposure to acidic pollutants have not been studied under foggy conditions; thus there is no directly relevant information from which to estimate the health risk. Indirectly relevant information is available from numerous studies of volunteers exposed to "acid fog precursors" under controlled conditions at less than 100% relative humidity. The effect of fog in modifying responses to inhaled acidic pollutants is difficult to predict: depending on circumstances, fog droplets might either increase or decrease the effective dose of pollutants to the lower respiratory tract. Fog inhalation per se may have unfavorable effects in some individuals. Sulfur dioxide is known to exacerbate airway constriction in exercising asthmatics, at exposure concentrations attainable in ambient air. Nitrogen dioxide has shown little untoward respiratory effect at ambient concentrations in most studies, although it has been suggested to increase bronchial reactivity. Sulfuric acid aerosol has shown no clear effects at concentrations within the ambient range. At somewhat higher levels, increased bronchial reactivity and change in mucociliary clearance have been suggested. Almost no information is available concerning nitric acid.

  1. Effects of wood smoke particles from wood-burning stoves on the respiratory health of atopic humans

    Directory of Open Access Journals (Sweden)

    Riddervold Ingunn

    2012-04-01

    Full Text Available Abstract Background There is growing evidence that particulate air pollution derived from wood stoves causes acute inflammation in the respiratory system, increases the incidence of asthma and other allergic diseases, and increases respiratory morbidity and mortality. The objective of this study was to evaluate acute respiratory effects from short-term wood smoke exposure in humans. Twenty non-smoking atopic volunteers with normal lung function and without bronchial responsiveness were monitored during three different experimental exposure sessions, aiming at particle concentrations of about 200 μg/m3, 400 μg/m3, and clean air as control exposure. A balanced cross-over design was used and participants were randomly allocated to exposure orders. Particles were generated in a wood-burning facility and added to a full-scale climate chamber where the participants were exposed for 3 hours under controlled environmental conditions. Health effects were evaluated in relation to: peak expiratory flow (PEF, forced expiratory volume in the first second (FEV1, and forced vital capacity (FVC. Furthermore, the effects were assessed in relation to changes in nasal patency and from markers of airway inflammation: fractional exhaled nitric oxide (FENO, exhaled breath condensate (EBC and nasal lavage (NAL samples were collected before, and at various intervals after exposure. Results No statistically significant effect of wood smoke exposure was found for lung function, for FENO, for NAL or for the nasal patency. Limited signs of airway inflammation were found in EBC. Conclusion In conclusion, short term exposure with wood smoke at a concentration normally found in a residential area with a high density of burning wood stoves causes only mild inflammatory response.

  2. Effects of wood smoke particles from wood-burning stoves on the respiratory health of atopic humans.

    Science.gov (United States)

    Riddervold, Ingunn Skogstad; Bønløkke, Jakob Hjort; Olin, Anna-Carin; Grønborg, Therese Koops; Schlünssen, Vivi; Skogstrand, Kristin; Hougaard, David; Massling, Andreas; Sigsgaard, Torben

    2012-04-30

    There is growing evidence that particulate air pollution derived from wood stoves causes acute inflammation in the respiratory system, increases the incidence of asthma and other allergic diseases, and increases respiratory morbidity and mortality. The objective of this study was to evaluate acute respiratory effects from short-term wood smoke exposure in humans. Twenty non-smoking atopic volunteers with normal lung function and without bronchial responsiveness were monitored during three different experimental exposure sessions, aiming at particle concentrations of about 200 μg/m(3), 400 μg/m(3), and clean air as control exposure. A balanced cross-over design was used and participants were randomly allocated to exposure orders. Particles were generated in a wood-burning facility and added to a full-scale climate chamber where the participants were exposed for 3 hours under controlled environmental conditions. Health effects were evaluated in relation to: peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC). Furthermore, the effects were assessed in relation to changes in nasal patency and from markers of airway inflammation: fractional exhaled nitric oxide (FENO), exhaled breath condensate (EBC) and nasal lavage (NAL) samples were collected before, and at various intervals after exposure. No statistically significant effect of wood smoke exposure was found for lung function, for FENO, for NAL or for the nasal patency. Limited signs of airway inflammation were found in EBC. In conclusion, short term exposure with wood smoke at a concentration normally found in a residential area with a high density of burning wood stoves causes only mild inflammatory response.

  3. Numerical Simulation of Air Flow in Realistic Model of Human Upper Airways

    Directory of Open Access Journals (Sweden)

    Jakub ELCNER

    2010-12-01

    Full Text Available This article deals with CFD calculations of flow patterns in a realistic model of the upper respiratory tract. RANS method was used for the calculation. The flow was solved as an unsteady one due to its nature. Two breathing cycles were simulated, 15 l/min which corresponds to the idle breathing mode and 30 l/min which corresponds to light activity. The model of upper airways consists of the oral cavity, larynx and trachea, which branches up to the fourth generation. Values of the velocity field distribution calculated are the basis for future calculations of aerosol transport and deposition in the human respiratory tract.

  4. Modeling Forces on the Human Body.

    Science.gov (United States)

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-01-01

    Presents five models of the human body as a mechanical system which can be used in introductory physics courses: human arms as levers, humans falling from small heights, a model of the human back, collisions during football, and the rotating gymnast. Gives ideas for discussions and activities, including Interactive Physics (TM) simulations. (WRM)

  5. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model

    Science.gov (United States)

    Walsh, Paul; Behrens, Nicole; Carvallo Chaigneau, Francisco R.; McEligot, Heather; Agrawal, Karan; Newman, John W.; Anderson, Mark; Gershwin, Laurel J.

    2016-01-01

    Background Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2) which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase. Hypotheses We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected. Methods We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il)-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed. Results One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (pibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen. Conclusions Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes. However lung

  6. Effects of formalin-inactivated respiratory syncytial virus (FI-RSV in the perinatal lamb model of RSV.

    Directory of Open Access Journals (Sweden)

    Rachel J Derscheid

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV conducted in the 1960's that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3-5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.

  7. Vicarious Learning from Human Models in Monkeys

    OpenAIRE

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was app...

  8. Modeling Associations between Principals' Reported Indoor Environmental Quality and Students' Self-Reported Respiratory Health Outcomes Using GLMM and ZIP Models.

    Science.gov (United States)

    Toyinbo, Oluyemi; Matilainen, Markus; Turunen, Mari; Putus, Tuula; Shaughnessy, Richard; Haverinen-Shaughnessy, Ulla

    2016-03-30

    The aim of this paper was to examine associations between school building characteristics, indoor environmental quality (IEQ), and health responses using questionnaire data from both school principals and students. From 334 randomly sampled schools, 4248 sixth grade students from 297 schools participated in a questionnaire. From these schools, 134 principals returned questionnaires concerning 51 IEQ related questions of their school. Generalized linear mixed models (GLMM) were used to study the associations between IEQ indicators and existence of self-reported upper respiratory symptoms, while hierarchical Zero Inflated Poisson (ZIP)-models were used to model the number of symptoms. Significant associations were established between existence of upper respiratory symptoms and unsatisfactory classroom temperature during the heating season (ORs 1.45 for too hot and cold, and 1.27 for too cold as compared to satisfactory temperature) and dampness or moisture damage during the year 2006-2007 (OR: 1.80 as compared to no moisture damage), respectively. The number of upper respiratory symptoms was significantly associated with inadequate ventilation and dampness or moisture damage. A higher number of missed school days due to respiratory infections were reported in schools with inadequate ventilation (RR: 1.16). The school level IEQ indicator variables described in this paper could explain a relatively large part of the school level variation observed in the self-reported upper respiratory symptoms and missed school days due to respiratory infections among students.

  9. A highly attenuated recombinant human respiratory syncytial virus lacking the G protein induces long-lasting protection in cotton rats

    Directory of Open Access Journals (Sweden)

    van Remmerden Yvonne

    2010-06-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (rRSV and an rRSV lacking the G gene (ΔG were constructed based on a clinical RSV isolate (strain 98-25147-X. Results Growth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for ΔG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days. Conclusion Collectively, the data indicate that a single dose immunization with the highly attenuated ΔG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since ΔG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.

  10. Source and role of diacylglycerol formed during phagocytosis of opsonized yeast particles and associated respiratory burst in human neutrophils

    International Nuclear Information System (INIS)

    Della Bianca, V.; Grzeskowiak, M.; Lissandrini, D.; Rossi, F.

    1991-01-01

    The results presented in this paper demonstrate that in human neutrophils phagocytosis of C3b/bi and IgG-opsonized yeast particles is associated with activation of phospholipase D and that this reaction is the main source of diglycerides. The demonstration is based upon the following findings: (1) the challenge of neutrophils with these opsonized particles was followed by a rapid formation of [3H]alkyl-phosphatidic acid [( 3H]alkyl-PA) and [3H]alkyl-diglyceride [( 3H]alkyl-DG) in cells labeled with [3H]alkyl-lyso-phosphatidylcholine; (2) in the presence of ethanol [3H]alkyl-phosphatidylethanol was formed, and accumulation of [3H]alkyl-PA and [3H]alkyl-DG was depressed; (3) propranolol, by inhibiting the dephosphorylation of [3H]alkyl-PA, completely inhibited the accumulation of [3H]alkyl-DG and depressed by about 75% the formation of diglyceride mass. Evidence is also presented that phagocytosis of C3b/bi and IgG-opsonized yeast particles and associated respiratory burst can take place independently of diglyceride formation and of the activity of this second messenger on protein kinase C. In fact: (a) propranolol while completely inhibited the formation of diglyceride mass did not modify either the phagocytosis or respiratory burst; (b) these two processes were insensitive to staurosporine

  11. Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China

    Directory of Open Access Journals (Sweden)

    Liu Wen-Kuan

    2011-12-01

    Full Text Available Abstract Background Human bocavirus (HBoV is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. Methods Throat swabs (n=2811 were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. Results HBoV DNA was detected in 65/2811 (2.3% samples, of which 61/1797 were from children (Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65. Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2% patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. Conclusions HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.

  12. Development of TaqMan RT-qPCR for the detection of type A human respiratory syncytial virus.

    Science.gov (United States)

    Abdel-Moneim, Ahmed S; Shehab, Gaber M; Alsulaimani, Adnan A; Al-Malky, Mater I R

    2017-06-01

    The human respiratory syncytial virus is a common respiratory pathogen in children. Improved diagnosis of the virus is dependent on the development of tools for the rapid detection and estimation of the viral loads. In the current study, RT-qPCR using TaqMan hydrolysis probe based on the F gene detection was developed to identify and quantify hRSV in clinical samples. The assay was validated by comparing the results with a commercially available RT-qPCR kit. The newly developed assay was sensitive in detecting hRSV positive samples (59/126) which were equivalent to those detected by the commercial kit (57/126) with a detection limit of 1 × 10 2 copies/mL. A high correlation was found between the results of the newly developed assay and the commercial one. It was concluded that the newly developed RT-qPCR assay can be used as a sensitive detection tool for hRSV-A. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Genome sequence of human adenovirus type 55, a re-emergent acute respiratory disease pathogen in China.

    Science.gov (United States)

    Zhang, Qiwei; Seto, Donald; Cao, Bin; Zhao, Suhui; Wan, Chengsong

    2012-11-01

    Human adenovirus type 55 (HAdV-B55) is an acute respiratory disease (ARD) pathogen first completely characterized in China (2006). This is a unique Trojan horse microbe with the virus neutralization attribute of a renal pathogen and the cell tropism and clinical attributes of a respiratory pathogen, bypassing herd immunity. It appeared to be an uncommon pathogen, with earlier putative, sporadic occurrences in Spain (1969) and Turkey (2004); these isolates were incompletely characterized using only two epitopes. Reported here is the genome of a second recent isolate (China, 2011), indicating that it may occur more frequently. The availability of this HAdV-B55 genome provides a foundation for studying adenovirus molecular evolution, the dynamics of epidemics, and patterns of pathogen emergence and re-emergence. These data facilitate studies to predict genome recombination between adenoviruses, as well as sequence divergence rates and hotspots, all of which are important for vaccine development and because HAdVs are used for epitope and/or gene delivery vectors.

  14. Local forearm and whole-body respiratory quotient in humans after an oral glucose load

    DEFF Research Database (Denmark)

    Simonsen, L; Bülow, J; Madsen, J

    1993-01-01

    The effects of an oral glucose load of 75 g on the local forearm and whole-body energy thermogenesis were measured in normal subjects during the 4 h after the glucose intake. Simultaneous assessment of substrate metabolism in the forearm was performed. Energy expenditure (EE) increased after...... the glucose load and had not returned to baseline level at the end of the experiment. Whole-body respiratory quotient (RQ) was, on average, 0.80 (SD 0.05) in the baseline condition and increased to a maximum of 0.91 (0.03) and then decreased to baseline level at the end of the experiment. The local forearm...... oxygen uptake increased 30 min after the glucose intake and remained elevated during the rest of the experiment. The carbon dioxide output from the forearm did not increase before 90 min after the glucose load. Consequently the local forearm RQ decreased significantly from a baseline value of 0.86 (0...

  15. Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru.

    Directory of Open Access Journals (Sweden)

    Andrew Wu

    Full Text Available The disease burden and risk factors for respiratory syncytial virus (RSV and human metapneumovirus (MPV infections among children living in remote, rural areas remain unclear.We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI, including lower respiratory tract infection (LRTI, were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression.Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05 among children with RSV (clinic 41% and hospital 5.3% and MPV ARI (38% and 3.5% when compared with other viral infections (23% and 0.7% and infections without virus detected (24% and 0.6%. In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03, the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38, residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents. Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01.In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses

  16. Pediatric Specialty Care Model for Management of Chronic Respiratory Failure: Cost and Savings Implications and Misalignment With Payment Models.

    Science.gov (United States)

    Graham, Robert J; McManus, Michael L; Rodday, Angie Mae; Weidner, Ruth Ann; Parsons, Susan K

    2018-02-03

    To describe program design, costs, and savings implications of a critical care-based care coordination model for medically complex children with chronic respiratory failure. All program activities and resultant clinical outcomes were tracked over 4 years using an adapted version of the Care Coordination Measurement Tool. Patient characteristics, program activity, and acute care resource utilization were prospectively documented in the adapted version of the Care Coordination Measurement Tool and retrospectively cross-validated with hospital billing data. Impact on total costs of care was then estimated based on program outcomes and nationally representative administrative data. Tertiary children's hospital. Critical Care, Anesthesia, Perioperative Extension and Home Ventilation Program enrollees. None. The program provided care for 346 patients and families over the study period. Median age at enrollment was 6 years with more than half deriving secondary respiratory failure from a primary neuromuscular disease. There were 11,960 encounters over the study period, including 1,202 home visits, 673 clinic visits, and 4,970 telephone or telemedicine encounters. Half (n = 5,853) of all encounters involved a physician and 45% included at least one care coordination activity. Overall, we estimated that program interventions were responsible for averting 556 emergency department visits and 107 hospitalizations. Conservative monetization of these alone accounted for annual savings of $1.2-2 million or $407/pt/mo net of program costs. Innovative models, such as extension of critical care services, for high-risk, high-cost patients can result in immediate cost savings. Evaluation of financial implications of comprehensive care for high-risk patients is necessary to complement clinical and patient-centered outcomes for alternative care models. When year-to-year cost variability is high and cost persistence is low, these savings can be estimated from documentation within care

  17. Effect of acute hypoxia on respiratory muscle fatigue in healthy humans.

    Science.gov (United States)

    Verges, Samuel; Bachasson, Damien; Wuyam, Bernard

    2010-08-11

    Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue. Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO2 = 80%) and hyperoxic (FiO2 = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P(di,tw)) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P(ga,tw)) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions. Hypoxia enhanced hyperpnoea-induced P(di,tw) and P(ga,tw) reductions both immediately after hyperpnoea (P(di,tw) : normoxia -22 +/- 7% vs hypoxia -34 +/- 8% vs hyperoxia -21 +/- 8%; P(ga,tw) : normoxia -17 +/- 7% vs hypoxia -26 +/- 10% vs hyperoxia -16 +/- 11%; all P hypoxia -16 +/- 8% vs hyperoxia -8 +/- 7%; P(ga,tw) : normoxia -13 +/- 6% vs hypoxia -21 +/- 9% vs hyperoxia -12 +/- 12%; all P hypoxia compared to normoxia and hyperoxia. These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O2 transport as during exercise in altitude or in hypoxemic patients.

  18. Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

    Directory of Open Access Journals (Sweden)

    Verges Samuel

    2010-08-01

    Full Text Available Abstract Background Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue. Methods Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern in normoxic, hypoxic (SpO2 = 80% and hyperoxic (FiO2 = 0.60 conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (Pdi,tw was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (Pga,tw was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions. Results Hypoxia enhanced hyperpnoea-induced Pdi,tw and Pga,tw reductions both immediately after hyperpnoea (Pdi,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; Pga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P di,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; Pga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P di,tw or Pga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia. Conclusions These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O2 transport as

  19. Molecular epidemiology and phylodynamics of the human respiratory syncytial virus fusion protein in northern Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsin Chi

    Full Text Available BACKGROUND AND AIMS: The glycoprotein (G protein and fusion protein (F protein of respiratory syncytial virus (RSV both show genetic variability, but few studies have examined the F protein gene. This study aimed to characterize the molecular epidemiology and phylodynamics of the F protein gene in clinical RSV strains isolated in northern Taiwan from 2000-2011. METHODS: RSV isolates from children presenting with acute respiratory symptoms between July 2000 and June 2011 were typed based on F protein gene sequences. Phylogeny construction and evaluation were performed using the neighbor-joining (NJ and maximum likelihood (ML methods. Phylodynamic patterns in RSV F protein genes were analyzed using the Bayesian Markov Chain Monte Carlo framework. Selection pressure on the F protein gene was detected using the Datamonkey website interface. RESULTS: From a total of 325 clinical RSV strains studied, phylogenetic analysis showed that 83 subgroup A strains (RSV-A could be further divided into three clusters, whereas 58 subgroup B strains (RSV-B had no significant clustering. Three amino acids were observed to differ between RSV-A and -B (positions 111, 113, and 114 in CTL HLA-B*57- and HLA-A*01-restricted epitopes. One positive selection site was observed in RSV-B, while none was observed in RSV-A. The evolution rate of the virus had very little change before 2000, then slowed down between 2000 and 2005, and evolved significantly faster after 2005. The dominant subtypes of RSV-A in each epidemic were replaced by different subtypes in the subsequent epidemic. CONCLUSIONS: Before 2004, RSV-A infections were involved in several small epidemics and only very limited numbers of strains evolved and re-emerged in subsequent years. After 2005, the circulating RSV-A strains were different from those of the previous years and continued evolving through 2010. Phylodynamic pattern showed the evolutionary divergence of RSV increased significantly in the recent 5

  20. Deformable human body model development

    Energy Technology Data Exchange (ETDEWEB)

    Wray, W.O.; Aida, T.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). A Deformable Human Body Model (DHBM) capable of simulating a wide variety of deformation interactions between man and his environment has been developed. The model was intended to have applications in automobile safety analysis, soldier survivability studies and assistive technology development for the disabled. To date, we have demonstrated the utility of the DHBM in automobile safety analysis and are currently engaged in discussions with the U.S. military involving two additional applications. More specifically, the DHBM has been incorporated into a Virtual Safety Lab (VSL) for automobile design under contract to General Motors Corporation. Furthermore, we have won $1.8M in funding from the U.S. Army Medical Research and Material Command for development of a noninvasive intracranial pressure measurement system. The proposed research makes use of the detailed head model that is a component of the DHBM; the project duration is three years. In addition, we have been contacted by the Air Force Armstrong Aerospace Medical Research Laboratory concerning possible use of the DHBM in analyzing the loads and injury potential to pilots upon ejection from military aircraft. Current discussions with Armstrong involve possible LANL participation in a comparison between DHBM and the Air Force Articulated Total Body (ATB) model that is the current military standard.

  1. 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

    NARCIS (Netherlands)

    R.S. Tang (Roderick); J.H. Schickli (Jeanne); M. MacPhail (Mia); F. Fernandes (Fiona); L. Bicha (Leenas); J. Spaete (Joshua); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); R. Spaete (Richard); A.A. Haller (Aurelia)

    2003-01-01

    textabstractA 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

  2. HumMod: A Modeling Environment for the Simulation of Integrative Human Physiology

    OpenAIRE

    Hester, Robert L.; Brown, Alison J.; Husband, Leland; Iliescu, Radu; Pruett, Drew; Summers, Richard; Coleman, Thomas G.

    2011-01-01

    Mathematical models and simulations are important tools in discovering key causal relationships governing physiological processes. Simulations guide and improve outcomes of medical interventions involving complex physiology. We developed HumMod, a Windows-based model of integrative human physiology. HumMod consists of 5000 variables describing cardiovascular, respiratory, renal, neural, endocrine, skeletal muscle and metabolic physiology. The model is constructed from empirical data obtained ...

  3. DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

    Science.gov (United States)

    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

  4. Diversity of aging of the immune system classified in the cotton rat (Sigmodon hispidus) model of human infectious diseases.

    NARCIS (Netherlands)

    Guichelaar, Teun; van Erp, Elisabeth A; Hoeboer, Jeroen; Smits, Noortje A M; van Els, Cécile A C M; Pieren, Daan K J; Luytjes, Willem

    2018-01-01

    Susceptibility and declined resistance to human pathogens like respiratory syncytial virus (RSV) at old age is well represented in the cotton rat (Sigmodon hispidus). Despite providing a preferred model of human infectious diseases, little is known about aging of its adaptive immune system. We aimed

  5. Vicarious learning from human models in monkeys.

    Science.gov (United States)

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  6. Vicarious learning from human models in monkeys.

    Directory of Open Access Journals (Sweden)

    Rossella Falcone

    Full Text Available We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  7. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects.

    Directory of Open Access Journals (Sweden)

    Galateja Jordakieva

    Full Text Available BACKGROUND AND AIMS: Specific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC. METHODS AND RESULTS: BALB/c mice (n = 20 were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10 or the non-specific antigen ovalbumin (OVA (n = 10. A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42 at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites. CONCLUSION: Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens

  8. Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

    Science.gov (United States)

    Leemans, A; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M L; Melero, J A; McLellan, J S; Graham, B S; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P

    2017-07-15

    Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are

  9. Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia.

    Directory of Open Access Journals (Sweden)

    Ans Timmermans

    Full Text Available Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77 presenting with influenza-like-illness (ILI at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV and EV71. Influenza was found in 168 cases (29% and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%. Western Cambodian H1N1(2009 isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation than to 13 Thai isolates (75.9% genome conservation, despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7% and parainfluenza virus (3.8%, while non-polio enteroviruses (10.3% were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in

  10. Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia.

    Science.gov (United States)

    Timmermans, Ans; Melendrez, Melanie C; Se, Youry; Chuang, Ilin; Samon, Nou; Uthaimongkol, Nichapat; Klungthong, Chonticha; Manasatienkij, Wudtichai; Thaisomboonsuk, Butsaya; Tyner, Stuart D; Rith, Sareth; Horm, Viseth Srey; Jarman, Richard G; Bethell, Delia; Chanarat, Nitima; Pavlin, Julie; Wongstitwilairoong, Tippa; Saingam, Piyaporn; El, But Sam; Fukuda, Mark M; Touch, Sok; Sovann, Ly; Fernandez, Stefan; Buchy, Philippe; Chanthap, Lon; Saunders, David

    2016-01-01

    Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light of an increasingly important role of permissive mutations in influenza virus evolution

  11. A Novel Large Animal Model of Acute Respiratory Distress Syndrome Induced by Mitochondrial Products.

    Science.gov (United States)

    Sanchez, Pablo G; Pasrija, Chetan; Mulligan, Matthew J; Wadhwa, Mandheer; Pratt, Diana L; Li, Tieluo; Gammie, James S; Kon, Zachary N; Pham, Si M; Griffith, Bartley P

    2017-12-01

    We aimed to create a reproducible lung injury model utilizing injection of mitochondrial damage-associated molecular products. Our goal was to characterize the pathophysiologic response to damage-associated molecular pattern mediated organ injury. There remain significant gaps in our understanding of acute respiratory distress syndrome, in part due to the lack of clinically applicable animal models of this disease. Animal models of noninfectious, tissue damage-induced lung injury are needed to understand the signals and responses associated with this injury. Ten pigs (35-45 kg) received an intravenous dose of disrupted mitochondrial products and were followed for 6 hours under general anesthesia. These animals were compared to a control group (n = 5) and a model of lung injury induced by bacterial products (lipopolysaccharide n = 5). Heart rate and temperature were significantly elevated in the mitochondrial product (204 ± 12 and 41 ± 1) and lipopolysaccharide groups (178 ± 18 and 42 ± 0.5) compared with controls (100 ± 13 and 38 ± 0.5) (P products and lipopolysaccharide groups compared with controls (170 ± 39, 196 ± 27, and 564 ± 75 mm Hg respectively, P = 0.001). Lung injury scoring of histological sections was significantly worse in mitochondrial and lipopolysaccharide groups compared with controls (mitochondrial-64 ± 6, lipopolysaccharide-54 ± 8, control-14 ± 1.5, P= 0.002). Our data demonstrated that the presence of mitochondrial products in the circulation leads to systemic inflammatory response and lung injury. In its acute phase lung injury induced by tissue or bacterial products is clinically indistinguishable.

  12. A Novel Respiratory Motion Perturbation Model Adaptable to Patient Breathing Irregularities

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Amy [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wei, Jie [Department of Computer Science, City College of New York, New York, New York (United States); Gaebler, Carl P.; Huang, Hailiang; Olek, Devin [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Li, Guang, E-mail: lig2@mskcc.org [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2016-12-01

    Purpose: To develop a physical, adaptive motion perturbation model to predict tumor motion using feedback from dynamic measurement of breathing conditions to compensate for breathing irregularities. Methods and Materials: A novel respiratory motion perturbation (RMP) model was developed to predict tumor motion variations caused by breathing irregularities. This model contained 2 terms: the initial tumor motion trajectory, measured from 4-dimensional computed tomography (4DCT) images, and motion perturbation, calculated from breathing variations in tidal volume (TV) and breathing pattern (BP). The motion perturbation was derived from the patient-specific anatomy, tumor-specific location, and time-dependent breathing variations. Ten patients were studied, and 2 amplitude-binned 4DCT images for each patient were acquired within 2 weeks. The motion trajectories of 40 corresponding bifurcation points in both 4DCT images of each patient were obtained using deformable image registration. An in-house 4D data processing toolbox was developed to calculate the TV and BP as functions of the breathing phase. The motion was predicted from the simulation 4DCT scan to the treatment 4DCT scan, and vice versa, resulting in 800 predictions. For comparison, noncorrected motion differences and the predictions from a published 5-dimensional model were used. Results: The average motion range in the superoinferior direction was 9.4 ± 4.4 mm, the average ΔTV ranged from 10 to 248 mm{sup 3} (−26% to 61%), and the ΔBP ranged from 0 to 0.2 (−71% to 333%) between the 2 4DCT scans. The mean noncorrected motion difference was 2.0 ± 2.8 mm between 2 4DCT motion trajectories. After applying the RMP model, the mean motion difference was reduced significantly to 1.2 ± 1.8 mm (P=.0018), a 40% improvement, similar to the 1.2 ± 1.8 mm (P=.72) predicted with the 5-dimensional model. Conclusions: A novel physical RMP model was developed with an average accuracy of 1.2 ± 1.8 mm for

  13. TU-F-17A-03: An Analytical Respiratory Perturbation Model for Lung Motion Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Li, G; Yuan, A [Memorial Sloan Kettering Cancer Center, New York, NY (United States); Wei, J [City College of New York, New York, NY (United States)

    2014-06-15

    Purpose: Breathing irregularity is common, causing unreliable prediction in tumor motion for correlation-based surrogates. Both tidal volume (TV) and breathing pattern (BP=ΔVthorax/TV, where TV=ΔVthorax+ΔVabdomen) affect lung motion in anterior-posterior and superior-inferior directions. We developed a novel respiratory motion perturbation (RMP) model in analytical form to account for changes in TV and BP in motion prediction from simulation to treatment. Methods: The RMP model is an analytical function of patient-specific anatomic and physiologic parameters. It contains a base-motion trajectory d(x,y,z) derived from a 4-dimensional computed tomography (4DCT) at simulation and a perturbation term Δd(ΔTV,ΔBP) accounting for deviation at treatment from simulation. The perturbation is dependent on tumor-specific location and patient-specific anatomy. Eleven patients with simulation and treatment 4DCT images were used to assess the RMP method in motion prediction from 4DCT1 to 4DCT2, and vice versa. For each patient, ten motion trajectories of corresponding points in the lower lobes were measured in both 4DCTs: one served as the base-motion trajectory and the other as the ground truth for comparison. In total, 220 motion trajectory predictions were assessed. The motion discrepancy between two 4DCTs for each patient served as a control. An established 5D motion model was used for comparison. Results: The average absolute error of RMP model prediction in superior-inferior direction is 1.6±1.8 mm, similar to 1.7±1.6 mm from the 5D model (p=0.98). Some uncertainty is associated with limited spatial resolution (2.5mm slice thickness) and temporal resolution (10-phases). Non-corrected motion discrepancy between two 4DCTs is 2.6±2.7mm, with the maximum of ±20mm, and correction is necessary (p=0.01). Conclusion: The analytical motion model predicts lung motion with accuracy similar to the 5D model. The analytical model is based on physical relationships, requires no

  14. The microbiota of the respiratory tract : Gatekeeper to respiratory health

    NARCIS (Netherlands)

    Man, Wing Ho; De Steenhuijsen Piters, Wouter A.A.; Bogaert, Debby

    2017-01-01

    The respiratory tract is a complex organ system that is responsible for the exchange of oxygen and carbon dioxide. The human respiratory tract spans from the nostrils to the lung alveoli and is inhabited by niche-specific communities of bacteria. The microbiota of the respiratory tract probably acts

  15. Human papillomaviruses and carcinogenesis: well-established and novel models.

    Science.gov (United States)

    Viarisio, Daniele; Gissmann, Lutz; Tommasino, Massimo

    2017-10-01

    Human papillomaviruses (HPVs) infect the cutaneous or mucosal epithelia and are classified phylogenetically as genera and species. Persistent infections by the mucosal high-risk (HR) HPV types from genus alpha are associated with cancer development of the genital and upper respiratory tracts. The products of two early genes, E6 and E7, are the major HR HPV oncoproteins, being essential in all steps of the carcinogenic process. Cutaneous beta HPV types are proposed, together with ultraviolet (UV) radiation, to promote non-melanoma skin cancer development. However, in contrast to the HR HPV types, beta HPV types appear to be required only at an early stage of carcinogenesis, facilitating the accumulation of UV-induced DNA mutations. Although findings in experimental models also suggest that beta HPV types and other carcinogens may synergize in the induction of malignancies, these possibilities need to be confirmed in human studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory; Joe, Jeffrey Clark [Idaho National Laboratory; Mandelli, Diego [Idaho National Laboratory

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  17. Genotoxic Effects of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    The nanomaterial industry has recently seen rapid growth, therefore, the risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is a fundamental aspect of hazard identification and regulatory guidance....

  18. The Genotoxicity of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    Due to the exponential growth of the nanomaterial industry, risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is an important aspect of hazard identification and regulatory guidance. However, this...

  19. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015 : A systematic review and modelling study

    NARCIS (Netherlands)

    Shi, Ting; McAllister, David A.; O'Brien, Katherine L.; Simoes, Eric A. F.; Madhi, Shabir A.; Gessner, Bradford D.; Polack, Fernando P.; Balsells, Evelyn; Acacio, Sozinho; Aguayo, Claudia; Alassani, Issifou; Ali, Asad; Antonio, Martin; Awasthi, Shally; Awori, Juliet O.; Azziz-Baumgartner, Eduardo; Baggett, Henry C.; Baillie, Vicky L.; Balmaseda, Angel; Barahona, Alfredo; Basnet, Sudha; Bassat, Quique; Basualdo, Wilma; Bigogo, Godfrey; Bont, Louis; Breiman, Robert F.; Brooks, W. Abdullah; Broor, Shobha; Bruce, Nigel; Bruden, Dana; Buchy, Philippe; Campbell, Stuart; Carosone-Link, Phyllis; Chadha, Mandeep; Chipeta, James; Chou, Monidarin; Clara, Wilfrido; Cohen, Cheryl; de Cuellar, Elizabeth; Dang, Duc Anh; Dash-yandag, Budragchaagiin; Deloria-Knoll, Maria; Dherani, Mukesh; Eap, Tekchheng; Ebruke, Bernard E.; Echavarria, Marcela; de Freitas Lázaro Emediato, Carla Cecília; Fasce, Rodrigo A.; Feikin, Daniel R.; Feng, Luzhao; Gentile, Angela; Gordon, Aubree; Goswami, Doli; Goyet, Sophie; Groome, Michelle J; Halasa, Natasha; Hirve, Siddhivinayak; Homaira, Nusrat; Howie, Stephen R.C.; Jara, Jorge; Jroundi, Imane; Kartasasmita, Cissy B.; Khuri-Bulos, Najwa; Kotloff, Karen L.; Krishnan, Anand; Libster, Romina; Lopez, Olga; Lucero, Marilla G.; Lucion, Florencia; Lupisan, Socorro P.; Marcone, Debora N.; McCracken, John P.; Mejia, Mario; Moisi, Jennifer C.; Montgomery, Joel M.; Moore, David P.; Moraleda, Cinta; Moyes, Jocelyn; Munywoki, Patrick; Mutyara, Kuswandewi; Nicol, Mark P.; Nokes, D. James; Nymadawa, Pagbajabyn; da Costa Oliveira, Maria Tereza; Oshitani, Histoshi; Pandey, Nitin; Paranhos-Baccalà, Gláucia; Phillips, Lia N.; Picot, Valentina Sanchez; Rahman, Mustafizur; Rakoto-Andrianarivelo, Mala; Rasmussen, Zeba A.; Rath, Barbara A.; Robinson, Annick; Romero, Candice; Russomando, Graciela; Salimi, Vahid; Sawatwong, Pongpun; Scheltema, Nienke; Schweiger, Brunhilde; Scott, J. Anthony G.; Seidenberg, Phil; Shen, Kunling; Singleton, Rosalyn; Sotomayor, Viviana; Strand, Tor A.; Sutanto, Agustinus; Sylla, Mariam; Tapia, Milagritos D.; Thamthitiwat, Somsak; Thomas, Elizabeth D.; Tokarz, Rafal; Turner, Claudia; Venter, Marietjie; Waicharoen, Sunthareeya; Wang, Jianwei; Watthanaworawit, Wanitda; Yoshida, Lay Myint; Yu, Hongjie; Zar, Heather J.; Campbell, Harry; Nair, Harish

    2017-01-01

    Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on

  20. Crowd Human Behavior for Modeling and Simulation

    Science.gov (United States)

    2009-08-06

    Crowd Human Behavior for Modeling and Simulation Elizabeth Mezzacappa, Ph.D. & Gordon Cooke, MEME Target Behavioral Response Laboratory, ARDEC...TYPE Conference Presentation 3. DATES COVERED 00-00-2008 to 00-00-2009 4. TITLE AND SUBTITLE Crowd Human Behavior for Modeling and Simulation...34understanding human behavior " and "model validation and verification" and will focus on modeling and simulation of crowds from a social scientist???s

  1. Biomechanical Modeling of the Human Head

    Science.gov (United States)

    2017-10-03

    Experimental Animal Models for Studies on the Mechanisms of Blast- Induced Neurotrauma,” Frontiers in Neurology 3, 30 (2012). 13. R. A. Bauman, G. Ling...modeling, of both humans and animals , has gained momentum for the investigation of traumatic brain injury. These models require both accurate geometric...between model predictions and experimental data. This report details model calibration for all materials identified in models of a human head and

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

    Science.gov (United States)

    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.

  3. Experimental determination of the regional deposition of aerosol particles in the human respiratory tract

    Energy Technology Data Exchange (ETDEWEB)

    Stahlhofen, W.; Gebhart, J.; Heyder, J.

    1980-06-01

    The experimental techniques and the results of inhalation studies with radioaerosols on normal non-smokers for mouth-breathing are described and discussed. Monodisperse iron oxide particles tagged with /sup 198/Au are produced with a spinning top generator in the aerodynamic size range between 1 to 10 ..mu..m. An aerosol inhalation apparatus enables the subjects to breathe under standardized conditions with respect to tidal volume and breathing frequency. The calculation of total deposition is based upon measurements of the number of in- and exhaled particles per breath by means of photometric methods and pneumotachography. The retention of the radioactive particles present in the body after aerosol administration is measured with a body counter designed and constructed for these experiments. Retention measurements as functions of time after inhalation are carried out in extrathoracic-, chest- and stomach-position. The body counter consists of four shielded NaF(Tl)-dectors. Characteristic feature of the body counter is its low sensitivity to neighboring organs and to neighboring regions within the respiratory tract. For the evaluation of extrathoracic deposition, the activity measured in the stomach immediately after inhalation is added to extrathoracic activity. The elimination of material from the chest is found to be much slower for the material deposited in the alveolar region than for the amount deposited in the tracheobronchial tree. This allows the intrathoracic deposition to be divided into tracheolbronchial and alveolar deposition by means of the different slopes of the normalized chest retention function. Different normalized chest retention functions are presented and analyzed with respect to their different elimination rats belonging to the tracheobronchial and alveolar region. Total, tracheobronchial, alveolar and extrathoracic deposition data are reported in the aerodynamic diameter range between 1 and 10 ..mu..m.

  4. Infection-enhancing lipopeptides do not improve intranasal immunization of cotton rats with a delta-G candidate live-attenuated human respiratory syncytial virus vaccine

    NARCIS (Netherlands)

    D.T. Nguyen (Tien); J. Boes (Jolande); G. van Amerongen (Geert); Y. van Remmerden (Yvonne); S. Yüksel (Selma); T. Guichelaar (Teun); A.D.M.E. Osterhaus (Albert); R.L. de Swart (Rik)

    2013-01-01

    textabstractDevelopment of live-attenuated human respiratory syncytial virus (HRSV) vaccines has proven to be difficult. Several vaccine candidates were found to be over-attenuated and displayed limited immunogenicity. Recently, we identified three synthetic cationic lipopeptides that enhanced

  5. Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases

    DEFF Research Database (Denmark)

    Papa, S.; De Rasmo, D.; Technikova-Dobrova, Z.

    2012-01-01

    In mammals, complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain has 31 supernumerary subunits in addition to the 14 conserved from prokaryotes to humans. Multiplicity of structural protein components, as well as of biogenesis factors, makes complex I a sensible pace-...

  6. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Salomonsen, Charlotte Mark; Breum, Solvej Østergaard; Larsen, Lars Erik

    2012-01-01

    Background Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with...

  7. A Novel Porcine Model of Septic Shock Induced by Acute Respiratory Distress Syndrome due to Methicillin-resistantStaphylococcus aureus.

    Science.gov (United States)

    Wang, Shuo; Wang, Jun-Yu; Wang, Tao; Hang, Chen-Chen; Shao, Rui; Li, Chun-Sheng

    2017-05-20

    Sepsis is one of the main causes of mortality in critically ill patients following progression to septic shock. To investigate the pathophysiologic changes of sepsis, we developed a novel porcine model of septic shock induced by acute respiratory distress syndrome (ARDS) due to methicillin-resistant Staphylococcus aureus(MRSA) pneumonia. Twenty-six male Landraces (Lvyuanweiye, Beijing, China) weighing 30 ± 2 kg were divided into four groups: sham group (SH; n = 5); cotton smoke inhalation group (SM; n = 6); MRSA pneumonia group (MR; n = 6); and septic shock group with cotton smoke inhalation + MRSA pneumonia (SS; n = 9). Extensive hemodynamics, oxygen dynamics, and lung function were monitored for 24 h following the injury or until death. Tissues were collected, and histopathology evaluations were carried out. Blood cultures from 6 of 9 animals in the SS group were positive for MRSA. Two hours following the injury, decreased mean arterial blood pressure (60-70 mmHg) and cardiac index (septic shock were only observed in the SS group but not significant in the other groups. The PO2/FiO2in the SM and SS groups decreased to 300 and 100, respectively. In the SS group, extravascular lung water index increased to 20 ml/kg, whereas thoracopulmonary compliance decreased to 10 ml/H2O after injury. Deterioration of pulmonary function in the SS group was more serious than the SM and MR groups. Severe lung injury in the SS group was confirmed by the histopathology evaluations. The lung injury confirmed by high-resolution thin-section computed tomography and histopathology in the SS group was more serious than those of other groups. In the present study, we developed a novel porcine model of septic shock induced by ARDS due to severe MRSA pneumonia with characteristic hyperdynamic and hypodynamic phases in 24 h, which mimicked the hemodynamic changing of septic shock in human.

  8. Detection of human rhinovirus C viral genome in blood among children with severe respiratory infections in the Philippines.

    Directory of Open Access Journals (Sweden)

    Naoko Fuji

    Full Text Available Human rhinovirus (HRV C was recently identified as the third species of HRV using a molecular technique. Infections caused by previously identified HRVs (A and B are thought to be limited to the respiratory tract; however, pathogenesis of HRVC is still largely unknown. A total of 816 nasopharyngeal swabs from hospitalized children with severe respiratory infections in the Philippines (May 2008-May 2009 were tested for HRV by reverse transcription polymerase chain reaction (RT-PCR, and 243 samples (29.8% were positive for HRV. Among these patients, serum samples were also tested to determine whether specific HRV species were associated with viremia. Only 30 serum samples (12.3% were positive for HRV. However, the HRV positive rates were different among HRV species, 3% (4/135 for HRVA, 0% (0/25 for HRVB, and 31% (26/83 for HRVC, and were the highest on 2 days after the onset of symptoms. These results suggest that HRVC may have a different pathogenicity and can more commonly cause viremia than HRVA and HRVB. Serum positive rates for HRV are affected by age, i.e., higher positive rates for those aged 1 year or more. HRVC that were detected from serum exhibited the same level of sequence diversity as those positive only for nasopharyngeal samples in phylogenetic analysis. However, all HRVA which were detected from serum were clustered in a monophyletic clade based on their 5' non-coding region (NCR sequences, which is closely related with a certain HRVC genotype (A2 in 5'-NCR. This finding suggests that the 5'NCR region may be associated with viremia.

  9. Human parainfluenza virus-associated respiratory tract infection among children and genetic analysis of HPIV-3 strains in Beijing, China.

    Directory of Open Access Journals (Sweden)

    Naiying Mao

    Full Text Available The relevance of human parainfluenza viruses (HPIVs to the epidemiology of acute respiratory infections (ARI in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs from hospitalized pediatric patients (age from 1 to 93 months in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase sequences of HPIV-3 indicated that three distinct clusters (A,B, and C were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%-100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.

  10. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

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    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  11. Genetic Variability of Group A Human Respiratory Syncytial Virus Strains Circulating in Germany from 1998 to 2007▿ †

    Science.gov (United States)

    Reiche, Janine; Schweiger, Brunhilde

    2009-01-01

    The variability between respiratory syncytial virus (RSV) strains is one of the features of RSV infections that might contribute to the ability of the virus to infect people repeatedly and cause yearly outbreaks. To study the molecular epidemiology of RSV, more than 1,400 RSV isolates from human nasopharyngeal aspirates or nasal or throat swabs from patients with respiratory illness were identified and differentiated by TaqMan reverse transcription-PCR into groups A and B. RSV group A was dominant in seven out of nine epidemic seasons. Phylogenetic analysis revealed that RSV group A genotypes GA2 and GA5 circulated from 1998 to 2007. Genotype GA7 was present in only two seasons (1999 to 2000 and 2002 to 2003). Comparison of the synonymous mutation/nonsynonymous mutation ratios showed greater evidence for selection pressure for genotype GA2 (1.18) than for GA5 (4.34). Partial protein sequences were predicted to encode G proteins of 298 amino acids in length and in a few cases of G proteins of 297 amino acids in length. Amino acid analysis also revealed genotype-specific amino acid substitutions: two substitutions for genotype GA2, seven for GA5, and three for GA7. Two to four putative, genotype-specific N-linked glycosylation sites were determined. Predicted O-glycosylation sites included 22 to 34 residues. This study provides for the first time data on the circulation pattern of RSV group A genotypes and their molecular characterization in Germany during nine consecutive epidemic seasons. PMID:19386848

  12. A phantom model demonstration of tomotherapy dose painting delivery, including managed respiratory motion without motion management

    Energy Technology Data Exchange (ETDEWEB)

    Kissick, Michael W; Mo Xiaohu; McCall, Keisha C; Mackie, Thomas R [Department of Medical Physics, Wisconsin Institutes for Medical Research, 111 Highland Avenue, University of Wisconsin-Madison, Madison, WI 53705 (United States); Schubert, Leah K [Radiation Oncology Department, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Westerly, David C, E-mail: mwkissick@wisc.ed [Department of Radiation Oncology, University of Colorado Denver, Aurora, CO 80045 (United States)

    2010-05-21

    The aim of the study was to demonstrate a potential alternative scenario for accurate dose-painting (non-homogeneous planned dose) delivery at 1 cm beam width with helical tomotherapy (HT) in the presence of 1 cm, three-dimensional, intra-fraction respiratory motion, but without any active motion management. A model dose-painting experiment was planned and delivered to the average position (proper phase of a 4DCT scan) with three spherical PTV levels to approximate dose painting to compensate for hypothetical hypoxia in a model lung tumor. Realistic but regular motion was produced with the Washington University 4D Motion Phantom. A small spherical Virtual Water(TM) phantom was used to simulate a moving lung tumor inside of the LUNGMAN(TM) anthropomorphic chest phantom to simulate realistic heterogeneity uncertainties. A piece of 4 cm Gafchromic EBT(TM) film was inserted into the 6 cm diameter sphere. TomoTherapy, Inc., DQA(TM) software was used to verify the delivery performed on a TomoTherapy Hi-Art II(TM) device. The dose uncertainty in the purposeful absence of motion management and in the absence of large, low frequency drifts (periods greater than the beam width divided by the couch velocity) or randomness in the breathing displacement yields very favorable results. Instead of interference effects, only small blurring is observed because of the averaging of many breathing cycles and beamlets and the avoidance of interference. Dose painting during respiration with helical tomotherapy is feasible in certain situations without motion management. A simple recommendation is to make respiration as regular as possible without low frequency drifting. The blurring is just small enough to suggest that it may be acceptable to deliver without motion management if the motion is equal to the beam width or smaller (at respiration frequencies) when registered to the average position.

  13. A phantom model demonstration of tomotherapy dose painting delivery, including managed respiratory motion without motion management

    International Nuclear Information System (INIS)

    Kissick, Michael W; Mo Xiaohu; McCall, Keisha C; Mackie, Thomas R; Schubert, Leah K; Westerly, David C

    2010-01-01

    The aim of the study was to demonstrate a potential alternative scenario for accurate dose-painting (non-homogeneous planned dose) delivery at 1 cm beam width with helical tomotherapy (HT) in the presence of 1 cm, three-dimensional, intra-fraction respiratory motion, but without any active motion management. A model dose-painting experiment was planned and delivered to the average position (proper phase of a 4DCT scan) with three spherical PTV levels to approximate dose painting to compensate for hypothetical hypoxia in a model lung tumor. Realistic but regular motion was produced with the Washington University 4D Motion Phantom. A small spherical Virtual Water(TM) phantom was used to simulate a moving lung tumor inside of the LUNGMAN(TM) anthropomorphic chest phantom to simulate realistic heterogeneity uncertainties. A piece of 4 cm Gafchromic EBT(TM) film was inserted into the 6 cm diameter sphere. TomoTherapy, Inc., DQA(TM) software was used to verify the delivery performed on a TomoTherapy Hi-Art II(TM) device. The dose uncertainty in the purposeful absence of motion management and in the absence of large, low frequency drifts (periods greater than the beam width divided by the couch velocity) or randomness in the breathing displacement yields very favorable results. Instead of interference effects, only small blurring is observed because of the averaging of many breathing cycles and beamlets and the avoidance of interference. Dose painting during respiration with helical tomotherapy is feasible in certain situations without motion management. A simple recommendation is to make respiration as regular as possible without low frequency drifting. The blurring is just small enough to suggest that it may be acceptable to deliver without motion management if the motion is equal to the beam width or smaller (at respiration frequencies) when registered to the average position.

  14. Diaphragm Muscle Adaptation to Sustained Hypoxia: Lessons from Animal Models with Relevance to High Altitude and Chronic Respiratory Diseases

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    Philip Lewis

    2016-12-01

    Full Text Available The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and, altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function.

  15. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison with hemorrhagic pneumonia due to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Salomonsen Charlotte M

    2012-11-01

    Full Text Available Abstract Background Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV has been shown to augment infection with P. aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. Findings We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR and for human RSV by a commercial real-time PCR. RSV was not found. Conclusions This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

  16. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa.

    Science.gov (United States)

    Salomonsen, Charlotte M; Breum, Solvej Ø; Larsen, Lars E; Jakobsen, Jeanette; Høiby, Niels; Hammer, Anne S

    2012-11-26

    Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with P. aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR) and for human RSV by a commercial real-time PCR. RSV was not found. This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

  17. Human-Dromedary Camel Interactions and the Risk of Acquiring Zoonotic Middle East Respiratory Syndrome Coronavirus Infection.

    Science.gov (United States)

    Gossner, C; Danielson, N; Gervelmeyer, A; Berthe, F; Faye, B; Kaasik Aaslav, K; Adlhoch, C; Zeller, H; Penttinen, P; Coulombier, D

    2016-02-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) cases without documented contact with another human MERS-CoV case make up 61% (517/853) of all reported cases. These primary cases are of particular interest for understanding the source(s) and route(s) of transmission and for designing long-term disease control measures. Dromedary camels are the only animal species for which there is convincing evidence that it is a host species for MERS-CoV and hence a potential source of human infections. However, only a small proportion of the primary cases have reported contact with camels. Other possible sources and vehicles of infection include food-borne transmission through consumption of unpasteurized camel milk and raw meat, medicinal use of camel urine and zoonotic transmission from other species. There are critical knowledge gaps around this new disease which can only be closed through traditional field epidemiological investigations and studies designed to test hypothesis regarding sources of infection and risk factors for disease. Since the 1960s, there has been a radical change in dromedary camel farming practices in the Arabian Peninsula with an intensification of the production and a concentration of the production around cities. It is possible that the recent intensification of camel herding in the Arabian Peninsula has increased the virus' reproductive number and attack rate in camel herds while the 'urbanization' of camel herding increased the frequency of zoonotic 'spillover' infections from camels to humans. It is reasonable to assume, although difficult to measure, that the sensitivity of public health surveillance to detect previously unknown diseases is lower in East Africa than in Saudi Arabia and that sporadic human cases may have gone undetected there. © 2014 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

  18. Respiratory epithelial cells require Toll-like receptor 4 for induction of Human β-defensin 2 by Lipopolysaccharide

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    McElvaney Noel

    2005-10-01

    Full Text Available Abstract Background The respiratory epithelium is a major portal of entry for pathogens and employs innate defense mechanisms to prevent colonization and infection. Induced expression of human β-defensin 2 (HBD2 represents a direct response by the epithelium to potential infection. Here we provide evidence for the critical role of Toll-like receptor 4 (TLR4 in lipopolysaccharide (LPS-induced HBD2 expression by human A549 epithelial cells. Methods Using RTPCR, fluorescence microscopy, ELISA and luciferase reporter gene assays we quantified interleukin-8, TLR4 and HBD2 expression in unstimulated or agonist-treated A549 and/or HEK293 cells. We also assessed the effect of over expressing wild type and/or mutant TLR4, MyD88 and/or Mal transgenes on LPS-induced HBD2 expression in these cells. Results We demonstrate that A549 cells express TLR4 on their surface and respond directly to Pseudomonas LPS with increased HBD2 gene and protein expression. These effects are blocked by a TLR4 neutralizing antibody or functionally inactive TLR4, MyD88 and/or Mal transgenes. We further implicate TLR4 in LPS-induced HBD2 production by demonstrating HBD2 expression in LPS non-responsive HEK293 cells transfected with a TLR4 expression plasmid. Conclusion This data defines an additional role for TLR4 in the host defense in the lung.

  19. Identification and Characterization of a Novel Alpaca Respiratory Coronavirus Most Closely Related to the Human Coronavirus 229E

    Directory of Open Access Journals (Sweden)

    Sharon K. Hietala

    2012-12-01

    Full Text Available In 2007, a novel coronavirus associated with an acute respiratory disease in alpacas (Alpaca Coronavirus, ACoV was isolated. Full-length genomic sequencing of the ACoV demonstrated the genome to be consistent with other Alphacoronaviruses. A putative additional open-reading frame was identified between the nucleocapsid gene and 3'UTR. The ACoV was genetically most similar to the common human coronavirus (HCoV 229E with 92.2% nucleotide identity over the entire genome. A comparison of spike gene sequences from ACoV and from HCoV-229E isolates recovered over a span of five decades showed the ACoV to be most similar to viruses isolated in the 1960’s to early 1980’s. The true origin of the ACoV is unknown, however a common ancestor between the ACoV and HCoV-229E appears to have existed prior to the 1960’s, suggesting virus transmission, either as a zoonosis or anthroponosis, has occurred between alpacas and humans.

  20. Identification of a Novel Human Papillomavirus by Metagenomic Analysis of Samples from Patients with Febrile Respiratory Illness

    Science.gov (United States)

    Mokili, John L.; Dutilh, Bas E.; Lim, Yan Wei; Schneider, Bradley S.; Taylor, Travis; Haynes, Matthew R.; Metzgar, David; Myers, Christopher A.; Blair, Patrick J.; Nosrat, Bahador; Wolfe, Nathan D.; Rohwer, Forest

    2013-01-01

    As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that the new HPV identified in this study clusters with previously described gamma papillomaviruses, sharing only 61.1% (whole genome) and 63.1% (L1) sequence identity with its closest relative in the Papillomavirus episteme (PAVE) database. This new virus was named HPV_SD2 pending official classification. The complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C) and contains 7 open reading frames (L2, L1, E6, E7, E1, E2 and E4) and a non-coding long control region (LCR) between L1 and E6. The metagenomic procedures, coupled with the bioinformatic methods described herein are well suited to detect small circular genomes such as those of human papillomaviruses. PMID:23554892

  1. Identification of a novel human papillomavirus by metagenomic analysis of samples from patients with febrile respiratory illness.

    Directory of Open Access Journals (Sweden)

    John L Mokili

    Full Text Available As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that the new HPV identified in this study clusters with previously described gamma papillomaviruses, sharing only 61.1% (whole genome and 63.1% (L1 sequence identity with its closest relative in the Papillomavirus episteme (PAVE database. This new virus was named HPV_SD2 pending official classification. The complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C and contains 7 open reading frames (L2, L1, E6, E7, E1, E2 and E4 and a non-coding long control region (LCR between L1 and E6. The metagenomic procedures, coupled with the bioinformatic methods described herein are well suited to detect small circular genomes such as those of human papillomaviruses.

  2. Respiratory Failure

    Science.gov (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, such as ... need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can't ...

  3. Experimental determination of the regional deposition of aerosol particles in the human respiratory tract.

    Science.gov (United States)

    Stahlhofen, W; Gebhart, J; Heyder, J

    1980-06-01

    The experimental techniques and the results of inhalation studies with radioaerosols on normal non-smokers for mouth-breathing are described and discussed. Monodisperse iron oxide particles tagged with 198Au are produced with a spinning top generator in the aerodynamic size range between 1 to 10 micrometers. An aerosol inhalation apparatus enables the subjects to breathe under standardized conditions with respect to tidal volume and breathing frequency. The calculation of total deposition is based upon measurements of the number of in- and exhaled particles per breath by means of photometric methods and pneumotachography. The retention of the radioactive particles present in the body after aerosol administration is measured with a body counter designed and constructed for these experiments. Retention measurements as functions of time after inhalation are carried out in extrathoracic-, chest- and stomach-position. The body counter consists of four shielded NaF(TI)-detectors. The geometrical arrangement, the collimation and the shielding of the four detectors have been optimized by computer calculations in such a way that the response of the counter is independent of the distribution of activity within the chest. Another characteristic feature of the body counter is its low sensitivity to neighboring organs and to neighboring regions within the respiratory tract. For the evaluation of extrathoracic deposition, the activity measured in the stomach immediately after inhalation is added to extrathoracic activity. The elimination of material from the chest (intrathoracic airways) is found to be much slower for the material deposited in the alveolar region (non-ciliated air spaces) than for the amount deposited in the tracheobronchial tree (ciliated airways). This allows the intrathoracic deposition to be divided into tracheobronchial and alveolar deposition by means of the different slopes of the normalized chest retention function. Different normalized chest retention

  4. Influence of Upper-Body Exercise on the Fatigability of Human Respiratory Muscles

    Science.gov (United States)

    TILLER, NICHOLAS B.; CAMPBELL, IAN G.; ROMER, LEE M.

    2017-01-01

    ABSTRACT Purpose Diaphragm and abdominal muscles are susceptible to contractile fatigue in response to high-intensity, whole-body exercise. This study assessed whether the ventilatory and mechanical loads imposed by high-intensity, upper-body exercise would be sufficient to elicit respiratory muscle fatigue. Methods Seven healthy men (mean ± SD; age = 24 ± 4 yr, peak O2 uptake [V˙O2peak] = 31.9 ± 5.3 mL·kg−1·min−1) performed asynchronous arm-crank exercise to exhaustion at work rates equivalent to 30% (heavy) and 60% (severe) of the difference between gas exchange threshold and V˙O2peak. Contractile fatigue of the diaphragm and abdominal muscles was assessed by measuring pre- to postexercise changes in potentiated transdiaphragmatic and gastric twitch pressures (Pdi,tw and Pga,tw) evoked by supramaximal magnetic stimulation of the cervical and thoracic nerves, respectively. Results Exercise time was 24.5 ± 5.8 min for heavy exercise and 9.8 ± 1.8 min for severe exercise. Ventilation over the final minute of heavy exercise was 73 ± 20 L·min−1 (39% ± 11% maximum voluntary ventilation) and 99 ± 19 L·min−1 (53% ± 11% maximum voluntary ventilation) for severe exercise. Mean Pdi,tw did not differ pre- to postexercise at either intensity (P > 0.05). Immediately (5–15 min) after severe exercise, mean Pga,tw was significantly lower than pre-exercise values (41 ± 13 vs 53 ± 15 cm H2O, P < 0.05), with the difference no longer significant after 25–35 min. Abdominal muscle fatigue (defined as ≥15% reduction in Pga,tw) occurred in 1/7 subjects after heavy exercise and 5/7 subjects after severe exercise. Conclusions High-intensity, upper-body exercise elicits significant abdominal, but not diaphragm, muscle fatigue in healthy men. The increased magnitude and prevalence of fatigue during severe-intensity exercise is likely due to additional (nonrespiratory) loading of the thorax. PMID:28288012

  5. Abnormal neutrophil-pulmonary interaction in the adult respiratory distress syndrome. Qualitative and quantitative assessment of pulmonary neutrophil kinetics in humans with in vivo 111indium neutrophil scintigraphy

    International Nuclear Information System (INIS)

    Warshawski, F.J.; Sibbald, W.J.; Driedger, A.A.; Cheung, H.

    1986-01-01

    In the absence of direct toxins, the majority of evidence from animal models suggests that neutrophils (PMN) are necessary for the full expression of the abnormal pulmonary permeability accompanying acute microvascular lung injury. We therefore studied the role of the PMN in the human correlate of this disease, the adult respiratory distress syndrome (ARDS), by assessing the pulmonary retention of infused autologous 111 Indium-labeled PMN (PMN-In). We evaluated 79 patients, prospectively categorized as: active ARDS (Aa; n = 30), active ARDS and concurrent corticosteroid therapy (As; n = 11), resolving ARDS (Ar; n = 13), sepsis without pulmonary edema (S; n = 7), and cardiac pulmonary edema (C; n = 18). This clinical separation was confirmed by retrospective analysis of associated measures of hemodynamic and respiratory dysfunction. We found that both analog scintigrams (positive/negative for diffuse pulmonary PMN-In sequestration) and computer-assisted quantitative analysis in 46 patients (T 1/2 of first hour demargination and percentage of peak activity/pixel/second remaining at 17 to 20 h) showed a significant rank order decrease in the pulmonary retention of labeled PMN-In through the Groups Aa----As----S----Ar----C. Our findings recognized aspects of in vivo PMN-In behavior that implied pathophysiologic differences between groups of critically ill patients in either the PMN themselves or in PMN-pulmonary endothelial interaction. This demonstrates the possibility of abnormal in vivo PMN-endothelial interaction in ARDS by virtue of the greater pulmonary localization of PMN in active ARDS versus resolving disease, septic non-ARDS states, and cardiac pulmonary edema

  6. Identification of Probiotic Strains from Human Milk in Breastfed Infants with Respiratory Infections

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    Neamtu Bogdan

    2014-12-01

    Full Text Available Isolation and industrial exploitation of probiotics from human milk is a goal for worldwide milk biotechnology centres because of their modulation effect on the immune system in infants and adults. In the proposed study we have analysed fermentation patterns of Lactobacilli isolated from human milk, the reliability of API 50 CH carbohydrate fermentation system and a possible link between lactose concentrations and fermentation profiles on carbohydrates. We had succesfully identified three species of Lactobacillus (paracasei ssp paracasei, fermentum, acidophilus and one unsatisfactory identification of Lactoccocus lactis ssp lactis. These strains had different carbohydrate fermentation patterns but with common characteristics and showed no statistically significant correlations between their carbohydrate metabolic trends and lactose concentrations in the milk samples.

  7. A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium

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    Berkhout Ben

    2005-02-01

    Full Text Available Abstract Background Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43 and 229E (HCoV-229E, SARS associated coronavirus (SARS-CoV and the recently identified human coronavirus NL63 (HCoV-NL63. In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. Methods Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. Results Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. Conclusions Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.

  8. Phrenic and hypoglossal nerve activity during respiratory response to hypoxia in 6-OHDA unilateral model of Parkinson's disease.

    Science.gov (United States)

    Andrzejewski, Kryspin; Budzińska, Krystyna; Kaczyńska, Katarzyna

    2017-07-01

    Parkinson's disease (PD) patients apart from motor dysfunctions exhibit respiratory disturbances. Their mechanism is still unknown and requires investigation. Our research was designed to examine the activity of phrenic (PHR) and hypoglossal (HG) nerves activity during a hypoxic respiratory response in the 6-hydroxydopamine (6-OHDA) model of PD. Male adult Wistar rats were injected unilaterally with 6-OHDA (20μg) or the vehicle into the right medial forebrain bundle (MFB). Two weeks after the surgery the activity of the phrenic and hypoglossal nerve was registered in anesthetized, vagotomized, paralyzed, and mechanically ventilated rats under normoxic and hypoxic conditions. Lesion effectiveness was confirmed by the cylinder test, performed before the MFB injection and 14days after, before the respiratory experiment. 6-OHDA lesioned animals showed a significant increase in normoxic inspiratory time. Expiratory time and total time of the respiratory cycle were prolonged in PD rats after hypoxia. The amplitude of the PHR activity and its minute activity were increased in comparison to the sham group at recovery time and during 30s of hypoxia. The amplitude of the HG activity was increased in response to hypoxia in 6-OHDA lesioned animals. The degeneration of dopaminergic neurons decreased the pre-inspiratory/inspiratory ratio of the hypoglossal burst amplitude during and after hypoxia. Unilateral MFB lesion changed the activity of the phrenic and hypoglossal nerves. The altered pre-inspiratory hypoglossal nerve activity indicates modifications to the central mechanisms controlling the activity of the HG nerve and may explain respiratory disorders seen in PD, i.e. apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  10. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

    International Nuclear Information System (INIS)

    Morton, Craig J.; Cameron, Rachel; Lawrence, Lynne J.; Lin Bo; Lowe, Melinda; Luttick, Angela; Mason, Anthony; McKimm-Breschkin, Jenny; Parker, Michael W.; Ryan, Jane; Smout, Michael; Sullivan, Jayne; Tucker, Simon P.; Young, Paul R.

    2003-01-01

    Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors

  11. Heat and Water Vapor Transfer in the Human Respiratory System at Hyperbaric Conditions.

    Science.gov (United States)

    1981-09-01

    monitor the pressure drop across the model nasal airway, i.e., between the trachea and the anterior nares. A modeling clay was utilized to restrict the...y .4.. I 150 REM Il I S RE’.]FI Fr I OF’’ ti I MUTE V4LI .ME IlH LI TEE’S PFE ’.SE 1160 1-=F𔃻 60 111 RT EM THE TEMF’, ,’,’’ HEHT TRANSFER IP [I0

  12. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    Directory of Open Access Journals (Sweden)

    Barker Peter E

    2007-05-01

    Full Text Available Abstract Background Sulfur mustard (SM is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE cells and bronchial/tracheal epithelial (BTE cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL-1β, IL-6, IL-8 and tumor necrosis factor (TNF, and expression of inducible nitric oxide synthase (iNOS were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1 fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory

  13. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    Science.gov (United States)

    Gao, Xiugong; Ray, Radharaman; Xiao, Yan; Barker, Peter E; Ray, Prabhati

    2007-01-01

    Background Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS) were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1) fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA) or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory cytokines and

  14. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

    OpenAIRE

    Cantin, A M; Fells, G A; Hubbard, R C; Crystal, R G

    1990-01-01

    We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-s...

  15. [Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

    Science.gov (United States)

    Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

    2014-12-08

    A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

  16. Rapid 3D in vivo 1H human lung respiratory imaging at 1.5 T using ultra-fast balanced steady-state free precession.

    Science.gov (United States)

    Pusterla, Orso; Bauman, Grzegorz; Wielpütz, Mark O; Nyilas, Sylvia; Latzin, Philipp; Heussel, Claus P; Bieri, Oliver

    2017-09-01

    To introduce a reproducible, nonenhanced 1H MRI method for rapid in vivo functional assessment of the whole lung at 1.5 Tesla (T). At different respiratory volumes, the pulmonary signal of ultra-fast steady-state free precession (ufSSFP) follows an adapted sponge model, characterized by a respiratory index α. From the model, α reflects local ventilation-related information, is virtually independent from the lung density and thus from the inspiratory phase and breathing amplitude. Respiratory α-mapping is evaluated for healthy volunteers and patients with obstructive lung disease from a set of five consecutive 3D ultra-fast steady-state free precession (ufSSFP) scans performed in breath-hold and at different inspiratory volumes. For the patients, α-maps were compared with CT, dynamic contrast-enhanced MRI (DCE-MRI), and Fourier decomposition (FD). In healthy volunteers, respiratory α-maps showed good reproducibility and were homogeneous on iso-gravitational planes, but showed a gravity-dependent respiratory gradient. In patients with obstructive pulmonary disease, the functional impairment observed in respiratory α-maps was associated with emphysematous regions present on CT images, perfusion defects observable on DCE-MRI, and impairments visualized on FD ventilation and perfusion maps. Respiratory α-mapping derived from multivolumetric ufSSFP provides insights into functional lung impairment and may serve as a reproducible and normative measure for clinical studies. Magn Reson Med 78:1059-1069, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  17. On scaling of human body models

    Directory of Open Access Journals (Sweden)

    Hynčík L.

    2007-10-01

    Full Text Available Human body is not an unique being, everyone is another from the point of view of anthropometry and mechanical characteristics which means that division of the human body population to categories like 5%-tile, 50%-tile and 95%-tile from the application point of view is not enough. On the other hand, the development of a particular human body model for all of us is not possible. That is why scaling and morphing algorithms has started to be developed. The current work describes the development of a tool for scaling of the human models. The idea is to have one (or couple of standard model(s as a base and to create other models based on these basic models. One has to choose adequate anthropometrical and biomechanical parameters that describe given group of humans to be scaled and morphed among.

  18. Computer modeling of human decision making

    Science.gov (United States)

    Gevarter, William B.

    1991-01-01

    Models of human decision making are reviewed. Models which treat just the cognitive aspects of human behavior are included as well as models which include motivation. Both models which have associated computer programs, and those that do not, are considered. Since flow diagrams, that assist in constructing computer simulation of such models, were not generally available, such diagrams were constructed and are presented. The result provides a rich source of information, which can aid in construction of more realistic future simulations of human decision making.

  19. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

    Energy Technology Data Exchange (ETDEWEB)

    John R. Ford

    2005-11-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

  20. Human Performance Models of Pilot Behavior

    Science.gov (United States)

    Foyle, David C.; Hooey, Becky L.; Byrne, Michael D.; Deutsch, Stephen; Lebiere, Christian; Leiden, Ken; Wickens, Christopher D.; Corker, Kevin M.

    2005-01-01

    Five modeling teams from industry and academia were chosen by the NASA Aviation Safety and Security Program to develop human performance models (HPM) of pilots performing taxi operations and runway instrument approaches with and without advanced displays. One representative from each team will serve as a panelist to discuss their team s model architecture, augmentations and advancements to HPMs, and aviation-safety related lessons learned. Panelists will discuss how modeling results are influenced by a model s architecture and structure, the role of the external environment, specific modeling advances and future directions and challenges for human performance modeling in aviation.

  1. Two-stage Bayesian model to evaluate the effect of air pollution on chronic respiratory diseases using drug prescriptions.

    Science.gov (United States)

    Blangiardo, Marta; Finazzi, Francesco; Cameletti, Michela

    2016-08-01

    Exposure to high levels of air pollutant concentration is known to be associated with respiratory problems which can translate into higher morbidity and mortality rates. The link between air pollution and population health has mainly been assessed considering air quality and hospitalisation or mortality data. However, this approach limits the analysis to individuals characterised by severe conditions. In this paper we evaluate the link between air pollution and respiratory diseases using general practice drug prescriptions for chronic respiratory diseases, which allow to draw conclusions based on the general population. We propose a two-stage statistical approach: in the first stage we specify a space-time model to estimate the monthly NO2 concentration integrating several data sources characterised by different spatio-temporal resolution; in the second stage we link the concentration to the β2-agonists prescribed monthly by general practices in England and we model the prescription rates through a small area approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    to be the prime model of inherited human disease and share 99% of their ... disturbances (including anxiety and depression) ..... Leibovici M, Safieddine S, Petit C (2008). Mouse models for human hereditary deafness. Curr. Top. Dev. Biol. 84:385-429. Levi YF, Meiner Z, Canello T, Frid K, Kovacs GG, Budka H, Avrahami.

  3. A randomized placebo controlled trial of ibuprofen for respiratory syncytial infection in a bovine model study

    Science.gov (United States)

    Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to ...

  4. Models to predict both sensible and latent heat transfer in the respiratory tract of Morada Nova sheep under semiarid tropical environment

    Science.gov (United States)

    Fonseca, Vinícius Carvalho; Saraiva, Edilson Paes; Maia, Alex Sandro Campos; Nascimento, Carolina Cardoso Nagib; da Silva, Josinaldo Araújo; Pereira, Walter Esfraim; Filho, Edgard Cavalcanti Pimenta; Almeida, Maria Elivânia Vieira

    2017-05-01

    The aim of this study was to build a prediction model both sensible and latent heat transfer by respiratory tract for Morada Nova sheep under field conditions in a semiarid tropical environment, using easily measured physiological and environmental parameters. Twelve dry Morada Nova ewes with an average of 3 ± 1.2 years old and average body weight of 32.76 ± 3.72 kg were used in a Latin square design 12 × 12 (12 days of records and 12 schedules). Tidal volume, respiratory rate, expired air temperature, and partial vapor pressure of the expired air were obtained from the respiratory facial mask and using a physiological measurement system. Ewes were evaluated from 0700 to 1900 h in each day under shade. A simple nonlinear model to estimate tidal volume as a function of respiratory rate was developed. Equation to estimate the expired air temperature was built, and the ambient air temperature was the best predictor together with relative humidity and ambient vapor pressure. In naturalized Morada Nova sheep, respiratory convection seems to be a mechanism of heat transfer of minor importance even under mild air temperature. Evaporation from the respiratory system increased together with ambient air temperature. At ambient air temperature, up to 35 °C respiratory evaporation accounted 90 % of the total heat lost by respiratory system, on average. Models presented here allow to estimate the heat flow from the respiratory tract for Morada Nova sheep bred in tropical region, using easily measured physiological and environmental traits as respiratory rate, ambient air temperature, and relative humidity.

  5. Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Mattingly, Kathleen A.; Klinge, Carolyn M. [University of Louisville School of Medicine, Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, Louisville, KY (United States)

    2012-04-15

    Endothelial dysfunction precedes cardiovascular disease and is accompanied by mitochondrial dysfunction. Here we tested the hypothesis that diesel exhaust particulate extracts (DEPEs), prepared from a truck run at different speeds and engine loads, would inhibit genomic estrogen receptor activation of nuclear respiratory factor-1 (NRF-1) transcription in human umbilical vein endothelial cells (HUVECs). Additionally, we examined how DEPEs affect NRF-1-regulated TFAM expression and, in turn, Tfam-regulated mtDNA-encoded cytochrome c oxidase subunit I (COI, MTCO1) and NADH dehydrogenase subunit I (NDI) expression as well as cell proliferation and viability. We report that 17{beta}-estradiol (E{sub 2}), 4-hydroxytamoxifen (4-OHT), and raloxifene increased NRF-1 transcription in HUVECs in an ER-dependent manner. DEPEs inhibited NRF-1 transcription, and this suppression was not ablated by concomitant treatment with E{sub 2}, 4-OHT, or raloxifene, indicating that the effect was not due to inhibition of ER activity. While E{sub 2} increased HUVEC proliferation and viability, DEPEs inhibited viability but not proliferation. Resveratrol increased NRF-1 transcription in an ER-dependent manner in HUVECs, and ablated DEPE inhibition of basal NRF-1 expression. Given that NRF-1 is a key nuclear transcription factor regulating genes involved in mitochondrial activity and biogenesis, these data suggest that DEPEs may adversely affect mitochondrial function leading to endothelial dysfunction and resveratrol may block these effects. (orig.)

  6. A Bayesian SIRS model for the analysis of respiratory syncytial virus in the region of Valencia, Spain.

    Science.gov (United States)

    Corberán-Vallet, Ana; Santonja, Francisco J

    2014-09-01

    We present a Bayesian stochastic susceptible-infected-recovered-susceptible (SIRS) model in discrete time to understand respiratory syncytial virus dynamics in the region of Valencia, Spain. A SIRS model based on ordinary differential equations has also been proposed to describe RSV dynamics in the region of Valencia. However, this continuous-time deterministic model is not suitable when the initial number of infected individuals is small. Stochastic epidemic models based on a probability of disease transmission provide a more natural description of the spread of infectious diseases. In addition, by allowing the transmission rate to vary stochastically over time, the proposed model provides an improved description of RSV dynamics. The Bayesian analysis of the model allows us to calculate both the posterior distribution of the model parameters and the posterior predictive distribution, which facilitates the computation of point forecasts and prediction intervals for future observations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Hidden Markov Models for Human Genes

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1997-01-01

    We analyse the sequential structure of human genomic DNA by hidden Markov models. We apply models of widely different design: conventional left-right constructs and models with a built-in periodic architecture. The models are trained on segments of DNA sequences extracted such that they cover com...

  8. Generation of fluoroscopic 3D images with a respiratory motion model based on an external surrogate signal.

    Science.gov (United States)

    Hurwitz, Martina; Williams, Christopher L; Mishra, Pankaj; Rottmann, Joerg; Dhou, Salam; Wagar, Matthew; Mannarino, Edward G; Mak, Raymond H; Lewis, John H

    2015-01-21

    Respiratory motion during radiotherapy can cause uncertainties in definition of the target volume and in estimation of the dose delivered to the target and healthy tissue. In this paper, we generate volumetric images of the internal patient anatomy during treatment using only the motion of a surrogate signal. Pre-treatment four-dimensional CT imaging is used to create a patient-specific model correlating internal respiratory motion with the trajectory of an external surrogate placed on the chest. The performance of this model is assessed with digital and physical phantoms reproducing measured irregular patient breathing patterns. Ten patient breathing patterns are incorporated in a digital phantom. For each patient breathing pattern, the model is used to generate images over the course of thirty seconds. The tumor position predicted by the model is compared to ground truth information from the digital phantom. Over the ten patient breathing patterns, the average absolute error in the tumor centroid position predicted by the motion model is 1.4 mm. The corresponding error for one patient breathing pattern implemented in an anthropomorphic physical phantom was 0.6 mm. The global voxel intensity error was used to compare the full image to the ground truth and demonstrates good agreement between predicted and true images. The model also generates accurate predictions for breathing patterns with irregular phases or amplitudes.

  9. Generation of fluoroscopic 3D images with a respiratory motion model based on an external surrogate signal

    International Nuclear Information System (INIS)

    Hurwitz, Martina; Williams, Christopher L; Mishra, Pankaj; Rottmann, Joerg; Dhou, Salam; Wagar, Matthew; Mannarino, Edward G; Mak, Raymond H; Lewis, John H

    2015-01-01

    Respiratory motion during radiotherapy can cause uncertainties in definition of the target volume and in estimation of the dose delivered to the target and healthy tissue. In this paper, we generate volumetric images of the internal patient anatomy during treatment using only the motion of a surrogate signal. Pre-treatment four-dimensional CT imaging is used to create a patient-specific model correlating internal respiratory motion with the trajectory of an external surrogate placed on the chest. The performance of this model is assessed with digital and physical phantoms reproducing measured irregular patient breathing patterns. Ten patient breathing patterns are incorporated in a digital phantom. For each patient breathing pattern, the model is used to generate images over the course of thirty seconds. The tumor position predicted by the model is compared to ground truth information from the digital phantom. Over the ten patient breathing patterns, the average absolute error in the tumor centroid position predicted by the motion model is 1.4 mm. The corresponding error for one patient breathing pattern implemented in an anthropomorphic physical phantom was 0.6 mm. The global voxel intensity error was used to compare the full image to the ground truth and demonstrates good agreement between predicted and true images. The model also generates accurate predictions for breathing patterns with irregular phases or amplitudes. (paper)

  10. Elucidative analysis and sequencing of two respiratory health monitoring methods to study the impact of varying atmospheric composition on human health

    Science.gov (United States)

    Awasthi, Amit; Hothi, Navjot; Kaur, Prabhjot; Singh, Nirankar; Chakraborty, Monojit; Bansal, Sangeeta

    2017-12-01

    Atmospheric composition of ambient air consists of different gases in definite proportion that affect the earth's climate and its ecological system. Due to varied anthropogenic reasons, this composition is changed, which ultimately have an impact on the health of living beings. For survival, the human respiratory system is one of the sensitive systems, which is easily and closely affected by the change in atmospheric composition of an external environment. Many studies have been conducted to quantify the effects of atmospheric pollution on human health by using different approaches. This article presents different scenario of studies conducted to evaluate the effects on different human groups. Differences between the studies conducted using spirometry and survey methods are presented in this article to extract a better sequence between these two methodologies. Many studies have been conducted to measure the respiratory status by evaluating the respiratory symptoms and hospital admissions. Limited numbers of studies are found with repeated spirometry on the same subjects for long duration to nullify the error arising due to decrease in efforts by the same subjects during manoeuvre of pulmonary function tests. Present study reveals the importance of methodological sequencing in order to obtain more authentic and reliable results. This study suggests that impacts of deteriorating atmospheric composition on human health can be more significantly studied if spirometry is done after survey analysis. The article also proposes that efficiency and authenticity of surveys involving health impacts will increase, if medical data information of patients is saved in hospitals in a proper format.

  11. SU-E-I-80: Quantification of Respiratory and Cardiac Motion Effect in SPECT Acquisitions Using Anthropomorphic Models: A Monte Carlo Simulation Study

    Energy Technology Data Exchange (ETDEWEB)

    Papadimitroulas, P; Kostou, T; Kagadis, G [University of Patras, Rion, Ahaia (Greece); Loudos, G [Technological Educational Institute of Athens, Egaleo, Attika (Greece)

    2015-06-15

    Purpose: The purpose of the present study was to quantify, evaluate the impact of cardiac and respiratory motion on clinical nuclear imaging protocols. Common SPECT and scintigraphic scans are studied using Monte Carlo (MC) simulations, comparing the resulted images with and without motion. Methods: Realistic simulations were executed using the GATE toolkit and the XCAT anthropomorphic phantom as a reference model for human anatomy. Three different radiopharmaceuticals based on 99mTc were studied, namely 99mTc-MDP, 99mTc—N—DBODC and 99mTc—DTPA-aerosol for bone, myocardium and lung scanning respectively. The resolution of the phantom was set to 3.5 mm{sup 3}. The impact of the motion on spatial resolution was quantified using a sphere with 3.5 mm diameter and 10 separate time frames, in the ECAM modeled SPECT scanner. Finally, respiratory motion impact on resolution and imaging of lung lesions was investigated. The MLEM algorithm was used for data reconstruction, while the literature derived biodistributions of the pharmaceuticals were used as activity maps in the simulations. Results: FWHM was extracted for a static and a moving sphere which was ∼23 cm away from the entrance of the SPECT head. The difference in the FWHM was 20% between the two simulations. Profiles in thorax were compared in the case of bone scintigraphy, showing displacement and blurring of the bones when respiratory motion was inserted in the simulation. Large discrepancies were noticed in the case of myocardium imaging when cardiac motion was incorporated during the SPECT acquisition. Finally the borders of the lungs are blurred when respiratory motion is included resulting to a dislocation of ∼2.5 cm. Conclusion: As we move to individualized imaging and therapy procedures, quantitative and qualitative imaging is of high importance in nuclear diagnosis. MC simulations combined with anthropomorphic digital phantoms can provide an accurate tool for applications like motion correction

  12. Modelling of polysomnographic respiratory measurements for artefact detection and signal restoration

    International Nuclear Information System (INIS)

    Rathnayake, S I; Abeyratne, U R; Hukins, C; Duce, B

    2008-01-01

    Polysomnography (PSG), which incorporates measures of sleep with measures of EEG arousal, air flow, respiratory movement and oxygenation, is universally regarded as the reference standard in diagnosing sleep-related respiratory diseases such as obstructive sleep apnoea syndrome. Over 15 channels of physiological signals are measured from a subject undergoing a typical overnight PSG session. The signals often suffer from data losses, interferences and artefacts. In a typical sleep scoring session, artefact-corrupted signal segments are visually detected and removed from further consideration. This is a highly time-consuming process, and subjective judgement is required for the job. During typical sleep scoring sessions, the target is the detection of segments of diagnostic interest, and signal restoration is not utilized for distorted segments. In this paper, we propose a novel framework for artefact detection and signal restoration based on the redundancy among respiratory flow signals. We focus on the air flow (thermistor sensors) and nasal pressure signals which are clinically significant in detecting respiratory disturbances. The method treats the respiratory system and other organs that provide respiratory-related inputs/outputs to it (e.g., cardiovascular, brain) as a possibly nonlinear coupled-dynamical system, and uses the celebrated Takens embedding theorem as the theoretical basis for signal prediction. Nonlinear prediction across time (self-prediction) and signals (cross-prediction) provides us with a mechanism to detect artefacts as unexplained deviations. In addition to detection, the proposed method carries the potential to correct certain classes of artefacts and restore the signal. In this study, we categorize commonly occurring artefacts and distortions in air flow and nasal pressure measurements into several groups and explore the efficacy of the proposed technique in detecting/recovering them. The results we obtained from a database of clinical

  13. Absence of respiratory inflammatory reaction of elemental sulfur using the California Pesticide Illness Database and a mouse model.

    Science.gov (United States)

    Lee, Kiyoung; Smith, Jodi L; Last, Jerold A

    2005-01-01

    Elemental sulfur, a natural substance, is used as a fungicide. Elemental sulfur is the most heavily used agricultural chemical in California. In 2003, annual sulfur usage in California was about 34% of the total weight of pesticide active ingredient used in production agriculture. Even though sulfur is mostly used in dust form, the respiratory health effects of elemental sulfur are not well documented. The purpose of this paper is to address the possible respiratory effect of elemental sulfur using the California Pesticide Illness Database and laboratory experiments with mice. We analyzed the California Pesticide Illness Database between 1991 and 2001. Among 127 reports of definite, probable, and possible illness involving sulfur, 21 cases (16%) were identified as respiratory related. A mouse model was used to examine whether there was an inflammatory or fibrotic response to elemental sulfur. Dust solutions were injected intratracheally into ovalbumin sensitized mice and lung damage was evaluated. Lung inflammatory response was analyzed via total lavage cell counts and differentials, and airway collagen content was analyzed histologically and biochemically. No significant differences from controls were seen in animals exposed to sulfur particles. The findings suggest that acute exposure of elemental sulfur itself may not cause an inflammatory reaction. However, further studies are needed to understand the possible health effects of chronic sulfur exposure and environmental weathering of sulfur dust.

  14. Model systems of human papillomavirus-associated disease.

    Science.gov (United States)

    Doorbar, John

    2016-01-01

    Human papillomaviruses (HPVs) cause a range of serious diseases, including the vast majority of cervical cancers, most anal cancers and around half of head and neck cancers. They are also responsible for troublesome benign epithelial lesions, including genital warts and laryngeal papillomas, and in some individuals HPVs lead to recurrent respiratory papillomatosis and other difficult-to-manage diseases. As a result, there is a great need for model systems that accurately mimic papillomavirus infections in humans. This is complicated by the diverse variety of HPVs, which now number over 200 types, and the different strategies they have evolved to persist in the population. The most well-developed models involve the culture of HPV-containing keratinocytes in organotypic raft culture, an approach which appears to accurately mimic the life cycle of several of the high-risk cancer-associated HPV types. Included amongst these are HPV16 and 18, which cause the majority of cervical cancers. The low-risk HPV types persist less well in tissue-culture models, and our ability to study the productive life cycle of these viruses is more limited. Although ongoing research is likely to improve this situation, animal models of papillomavirus disease can provide considerable basic information as to how lesions form, regress and can be controlled by the immune system. The best studied are cottontail rabbit papillomavirus, rabbit oral papillomavirus and, more recently, mouse papillomavirus (MmuPV), the last of which is providing exciting new insights into viral tropisms and immune control. In addition, transgenic models of disease have helped us to understand the consequences of persistent viral gene expression and the importance of co-factors such as hormones and UV irradiation in the development of neoplasia and cancer. It is hoped that such disease models will eventually lead us to better understanding and better treatments for human disease. Copyright © 2015 Pathological Society

  15. Human Centered Hardware Modeling and Collaboration

    Science.gov (United States)

    Stambolian Damon; Lawrence, Brad; Stelges, Katrine; Henderson, Gena

    2013-01-01

    In order to collaborate engineering designs among NASA Centers and customers, to in clude hardware and human activities from multiple remote locations, live human-centered modeling and collaboration across several sites has been successfully facilitated by Kennedy Space Center. The focus of this paper includes innovative a pproaches to engineering design analyses and training, along with research being conducted to apply new technologies for tracking, immersing, and evaluating humans as well as rocket, vehic le, component, or faci lity hardware utilizing high resolution cameras, motion tracking, ergonomic analysis, biomedical monitoring, wor k instruction integration, head-mounted displays, and other innovative human-system integration modeling, simulation, and collaboration applications.

  16. SU-F-J-138: An Extension of PCA-Based Respiratory Deformation Modeling Via Multi-Linear Decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Iliopoulos, AS; Sun, X [Duke University, Durham, North Carolina (United States); Pitsianis, N [Aristotle University of Thessaloniki (Greece); Duke University, Durham, North Carolina (United States); Yin, FF; Ren, L

    2016-06-15

    Purpose: To address and lift the limited degree of freedom (DoF) of globally bilinear motion components such as those based on principal components analysis (PCA), for encoding and modeling volumetric deformation motion. Methods: We provide a systematic approach to obtaining a multi-linear decomposition (MLD) and associated motion model from deformation vector field (DVF) data. We had previously introduced MLD for capturing multi-way relationships between DVF variables, without being restricted by the bilinear component format of PCA-based models. PCA-based modeling is commonly used for encoding patient-specific deformation as per planning 4D-CT images, and aiding on-board motion estimation during radiotherapy. However, the bilinear space-time decomposition inherently limits the DoF of such models by the small number of respiratory phases. While this limit is not reached in model studies using analytical or digital phantoms with low-rank motion, it compromises modeling power in the presence of relative motion, asymmetries and hysteresis, etc, which are often observed in patient data. Specifically, a low-DoF model will spuriously couple incoherent motion components, compromising its adaptability to on-board deformation changes. By the multi-linear format of extracted motion components, MLD-based models can encode higher-DoF deformation structure. Results: We conduct mathematical and experimental comparisons between PCA- and MLD-based models. A set of temporally-sampled analytical trajectories provides a synthetic, high-rank DVF; trajectories correspond to respiratory and cardiac motion factors, including different relative frequencies and spatial variations. Additionally, a digital XCAT phantom is used to simulate a lung lesion deforming incoherently with respect to the body, which adheres to a simple respiratory trend. In both cases, coupling of incoherent motion components due to a low model DoF is clearly demonstrated. Conclusion: Multi-linear decomposition can

  17. Thresholds in chemical respiratory sensitisation.

    Science.gov (United States)

    Cochrane, Stella A; Arts, Josje H E; Ehnes, Colin; Hindle, Stuart; Hollnagel, Heli M; Poole, Alan; Suto, Hidenori; Kimber, Ian

    2015-07-03

    There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the

  18. Modeling of Respiratory System Dysfunction Among Nuclear Workers: A Preliminary Study

    OpenAIRE

    Belyaeva, Z.D.; Osovets, S.V.; Scott, B.R.; Zhuntova, G.V.; Grigoryeva, E.S.

    2008-01-01

    Numerous studies have reported on cancers among Mayak Production Association (PA) nuclear workers. Other studies have reported on serious deterministic effects of large radiation doses for the same population. This study relates to deterministic effects (respiratory system dysfunction) in Mayak workers after relatively small chronic radiation doses (alpha plus gamma). Because cigarette smoke is a confounding factor, we also account for smoking effects. Here we present a new empirical mathemat...

  19. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

    Science.gov (United States)

    Shi, Ting; McAllister, David A; O'Brien, Katherine L; Simoes, Eric A F; Madhi, Shabir A; Gessner, Bradford D; Polack, Fernando P; Balsells, Evelyn; Acacio, Sozinho; Aguayo, Claudia; Alassani, Issifou; Ali, Asad; Antonio, Martin; Awasthi, Shally; Awori, Juliet O; Azziz-Baumgartner, Eduardo; Baggett, Henry C; Baillie, Vicky L; Balmaseda, Angel; Barahona, Alfredo; Basnet, Sudha; Bassat, Quique; Basualdo, Wilma; Bigogo, Godfrey; Bont, Louis; Breiman, Robert F; Brooks, W Abdullah; Broor, Shobha; Bruce, Nigel; Bruden, Dana; Buchy, Philippe; Campbell, Stuart; Carosone-Link, Phyllis; Chadha, Mandeep; Chipeta, James; Chou, Monidarin; Clara, Wilfrido; Cohen, Cheryl; de Cuellar, Elizabeth; Dang, Duc-Anh; Dash-Yandag, Budragchaagiin; Deloria-Knoll, Maria; Dherani, Mukesh; Eap, Tekchheng; Ebruke, Bernard E; Echavarria, Marcela; de Freitas Lázaro Emediato, Carla Cecília; Fasce, Rodrigo A; Feikin, Daniel R; Feng, Luzhao; Gentile, Angela; Gordon, Aubree; Goswami, Doli; Goyet, Sophie; Groome, Michelle; Halasa, Natasha; Hirve, Siddhivinayak; Homaira, Nusrat; Howie, Stephen R C; Jara, Jorge; Jroundi, Imane; Kartasasmita, Cissy B; Khuri-Bulos, Najwa; Kotloff, Karen L; Krishnan, Anand; Libster, Romina; Lopez, Olga; Lucero, Marilla G; Lucion, Florencia; Lupisan, Socorro P; Marcone, Debora N; McCracken, John P; Mejia, Mario; Moisi, Jennifer C; Montgomery, Joel M; Moore, David P; Moraleda, Cinta; Moyes, Jocelyn; Munywoki, Patrick; Mutyara, Kuswandewi; Nicol, Mark P; Nokes, D James; Nymadawa, Pagbajabyn; da Costa Oliveira, Maria Tereza; Oshitani, Histoshi; Pandey, Nitin; Paranhos-Baccalà, Gláucia; Phillips, Lia N; Picot, Valentina Sanchez; Rahman, Mustafizur; Rakoto-Andrianarivelo, Mala; Rasmussen, Zeba A; Rath, Barbara A; Robinson, Annick; Romero, Candice; Russomando, Graciela; Salimi, Vahid; Sawatwong, Pongpun; Scheltema, Nienke; Schweiger, Brunhilde; Scott, J Anthony G; Seidenberg, Phil; Shen, Kunling; Singleton, Rosalyn; Sotomayor, Viviana; Strand, Tor A; Sutanto, Agustinus; Sylla, Mariam; Tapia, Milagritos D; Thamthitiwat, Somsak; Thomas, Elizabeth D; Tokarz, Rafal; Turner, Claudia; Venter, Marietjie; Waicharoen, Sunthareeya; Wang, Jianwei; Watthanaworawit, Wanitda; Yoshida, Lay-Myint; Yu, Hongjie; Zar, Heather J; Campbell, Harry; Nair, Harish

    2017-09-02

    We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. Globally, RSV is a common cause

  20. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  1. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...

  2. Genetics, recombination and clinical features of human rhinovirus species C (HRV-C infections; interactions of HRV-C with other respiratory viruses.

    Directory of Open Access Journals (Sweden)

    Anne Wisdom

    Full Text Available To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV, 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%. Infections predominantly targeted the very young (median age 6-12 months; 80% of infections in those <2 years, occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT and upper respiratory tract (URT disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV in both disease presentations (6.9% and 7.8% of all cases respectively. HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5'untranslated region (5'UTR, the majority grouped with species A (n = 96; 68%, described as HRV-Ca, the remainder forming a phylogenetically distinct 5'UTR group (HRV-Cc. Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to

  3. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System, Phase II: Dodecahedral Micro-Model

    Energy Technology Data Exchange (ETDEWEB)

    Freed, Alan D.; Einstein, Daniel R.; Carson, James P.; Jacob, Rick E.

    2012-03-01

    In the first year of this contractual effort a hypo-elastic constitutive model was developed and shown to have great potential in modeling the elastic response of parenchyma. This model resides at the macroscopic level of the continuum. In this, the second year of our support, an isotropic dodecahedron is employed as an alveolar model. This is a microscopic model for parenchyma. A hopeful outcome is that the linkage between these two scales of modeling will be a source of insight and inspiration that will aid us in the final year's activity: creating a viscoelastic model for parenchyma.

  4. Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection.

    Directory of Open Access Journals (Sweden)

    Tomoki Yoshikawa

    2010-01-01

    Full Text Available Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated coronavirus (SARS-CoV. Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarray-based functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NFkappaB, activator protein (AP-1, and interferon regulatory factor (IRF-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i., resulting in the activation of many antiviral genes, including interferon (IFN-beta, -lambdas, inflammatory mediators, and many IFN-stimulated genes (ISGs. We also showed, for the first time, that IFN-beta and IFN-lambdas were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS.

  5. The Human-Artifact Model

    DEFF Research Database (Denmark)

    Bødker, Susanne; Klokmose, Clemens Nylandsted

    2011-01-01

    needs to support such development through concepts and methods. This leads to a methodological approach that focuses on new artifacts to supplement and substitute existing artifacts. Through a design case, we develop the methodological approach and illustrate how the human–artifact model can be applied...... to analyze present artifacts and to design future ones. The model is used to structure such analysis and to reason about findings while providing leverage from activity theoretical insights on mediation, dialectics, and levels of activity....

  6. Real-time prediction of respiratory motion based on a local dynamic model in an augmented space.

    Science.gov (United States)

    Hong, S-M; Jung, B-H; Ruan, D

    2011-03-21

    Motion-adaptive radiotherapy aims to deliver ablative radiation dose to the tumor target with minimal normal tissue exposure, by accounting for real-time target movement. In practice, prediction is usually necessary to compensate for system latency induced by measurement, communication and control. This work focuses on predicting respiratory motion, which is most dominant for thoracic and abdominal tumors. We develop and investigate the use of a local dynamic model in an augmented space, motivated by the observation that respiratory movement exhibits a locally circular pattern in a plane augmented with a delayed axis. By including the angular velocity as part of the system state, the proposed dynamic model effectively captures the natural evolution of respiratory motion. The first-order extended Kalman filter is used to propagate and update the state estimate. The target location is predicted by evaluating the local dynamic model equations at the required prediction length. This method is complementary to existing work in that (1) the local circular motion model characterizes 'turning', overcoming the limitation of linear motion models; (2) it uses a natural state representation including the local angular velocity and updates the state estimate systematically, offering explicit physical interpretations; (3) it relies on a parametric model and is much less data-satiate than the typical adaptive semiparametric or nonparametric method. We tested the performance of the proposed method with ten RPM traces, using the normalized root mean squared difference between the predicted value and the retrospective observation as the error metric. Its performance was compared with predictors based on the linear model, the interacting multiple linear models and the kernel density estimator for various combinations of prediction lengths and observation rates. The local dynamic model based approach provides the best performance for short to medium prediction lengths under relatively

  7. Human BDCM Mulit-Route PBPK Model

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set contains the code for the BDCM human multi-route model written in the programming language acsl. The final published manuscript is provided since it...

  8. Modeling Human Cancers in Drosophila.

    Science.gov (United States)

    Sonoshita, M; Cagan, R L

    2017-01-01

    Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools. © 2017 Elsevier Inc. All rights reserved.

  9. Modeling human learning involved in car driving

    OpenAIRE

    Wewerinke, P.H.

    1994-01-01

    In this paper, car driving is considered at the level of human tracking and maneuvering in the context of other traffic. A model analysis revealed the most salient features determining driving performance and safety. Learning car driving is modelled based on a system theoretical approach and based on a neural network approach. The aim of this research is to assess the relative merit of both approaches to describe human learning behavior in car driving specifically and in operating dynamic sys...

  10. Deficiency of GABAergic synaptic inhibition in the Kölliker-Fuse area underlies respiratory dysrhythmia in a mouse model of Rett syndrome.

    Science.gov (United States)

    Abdala, Ana Paula; Toward, Marie A; Dutschmann, Mathias; Bissonnette, John M; Paton, Julian F R

    2016-01-01

    Life threatening breathing irregularity and central apnoeas are highly prevalent in children suffering from Rett syndrome. Abnormalities in inhibitory synaptic transmission have been associated with the physiopathology of this syndrome, and may underlie the respiratory disorder. In a mouse model of Rett syndrome, GABAergic terminal projections are markedly reduced in the Kölliker-Fuse nucleus (KF) in the dorsolateral pons, an important centre for control of respiratory rhythm regularity. Administration of a drug that augments endogenous GABA localized to this region of the pons reduced the incidence of apnoea and the respiratory irregularity of Rett female mice. Conversely, the respiratory disorder was recapitulated by blocking GABAergic transmission in the KF area of healthy rats. This study helps us understand the mechanism for generation of respiratory abnormality in Rett syndrome, pinpoints a brain site responsible and provides a clear anatomical target for the development of a translatable drug treatment. Central apnoeas and respiratory irregularity are a common feature in Rett syndrome (RTT), a neurodevelopmental disorder most often caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2). We used a MECP2 deficient mouse model of RTT as a strategy to obtain insights into the neurobiology of the disease and into mechanisms essential for respiratory rhythmicity during normal breathing. Previously, we showed that, systemic administration of a GABA reuptake blocker in MECP2 deficient mice markedly reduced the occurrence of central apnoeas. Further, we found that, during central apnoeas, post-inspiratory drive (adductor motor) to the upper airways was enhanced in amplitude and duration in Mecp2 heterozygous female mice. Since the pontine Kölliker-Fuse area (KF) drives post-inspiration, suppresses inspiration, and can reset the respiratory oscillator phase, we hypothesized that synaptic inhibition in this area is essential for respiratory rhythm

  11. Estimating intratidal nonlinearity of respiratory system mechanics: a model study using the enhanced gliding-SLICE method

    International Nuclear Information System (INIS)

    Schumann, Stefan; Burcza, Boris; Guttmann, Josef; Haberthür, Christoph; Lichtwarck-Aschoff, Michael

    2009-01-01

    In the clinical situation and in most research work, the analysis of respiratory system mechanics is limited to the estimation of single-value compliances during static or quasi-static conditions. In contrast, our SLICE method analyses intratidal nonlinearity under the dynamic conditions of mechanical ventilation by calculating compliance and resistance for six conjoined volume portions (slices) of the pressure–volume loop by multiple linear regression analysis. With the gliding-SLICE method we present a new approach to determine continuous intratidal nonlinear compliance. The performance of the gliding-SLICE method was tested both in computer simulations and in a physical model of the lung, both simulating different intratidal compliance profiles. Compared to the original SLICE method, the gliding-SLICE method resulted in smaller errors when calculating the compliance or pressure course (all p 2 O s L −1 to 0.8 ± 0.3 cmH 2 O s L −1 (mathematical model) and from 7.2 ± 3.9 cmH 2 O s L −1 to 0.4 ± 0.2 cmH 2 O s L −1 (physical model) (all p < 0.001). We conclude that the new gliding-SLICE method allows detailed assessment of intratidal nonlinear respiratory system mechanics without discontinuity error

  12. Respiratory system model for quasistatic pulmonary pressure-volume (P-V) curve: inflation-deflation loop analyses.

    Science.gov (United States)

    Amini, R; Narusawa, U

    2008-06-01

    A respiratory system model (RSM) is developed for the deflation process of a quasistatic pressure-volume (P-V) curve, following the model for the inflation process reported earlier. In the RSM of both the inflation and the deflation limb, a respiratory system consists of a large population of basic alveolar elements, each consisting of a piston-spring-cylinder subsystem. A normal distribution of the basic elements is derived from Boltzmann statistical model with the alveolar closing (opening) pressure as the distribution parameter for the deflation (inflation) process. An error minimization by the method of least squares applied to existing P-V loop data from two different data sources confirms that a simultaneous inflation-deflation analysis is required for an accurate determination of RSM parameters. Commonly used terms such as lower inflection point, upper inflection point, and compliance are examined based on the P-V equations, on the distribution function, as well as on the geometric and physical properties of the basic alveolar element.

  13. Variable Ventilation Improved Respiratory System Mechanics and Ameliorated Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion.

    Science.gov (United States)

    Soluri-Martins, André; Moraes, Lillian; Santos, Raquel S; Santos, Cintia L; Huhle, Robert; Capelozzi, Vera L; Pelosi, Paolo; Silva, Pedro L; de Abreu, Marcelo Gama; Rocco, Patricia R M

    2017-01-01

    Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV ( n = 6/group) [tidal volume (V T ) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH 2 O, fraction of inspired oxygen (FiO 2 ) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V T values ( n = 1200; mean V T = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH 2 0/ml and 2.0 ± 0.8 cmH 2 0/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and

  14. The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*

    Science.gov (United States)

    2014-01-01

    the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document “Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)” of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document – produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise –after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,‘case-finding’approach; assessment of the individual’s level of risk of COPD; use of short questionnaires for an initial screening based on symptoms; use of simple spirometry for the second level of screening); b) it identifies possible ways of including these activities within primary care practice; c) it places early diagnosis within the “systemic”, consequential management of chronic respiratory diseases, which will be briefly described with the aid of schemes taken from the Italian and international reference documents. PMID:25473523

  15. Inhalation exposure to sulfur mustard in the guinea pig model: Clinical, biochemical and histopathological characterization of respiratory injuries

    International Nuclear Information System (INIS)

    Allon, Nahum; Amir, Adina; Manisterski, Eliau; Rabinovitz, Ishay; Dachir, Shlomit; Kadar, Tamar

    2009-01-01

    Guinea pigs (GP) were exposed (head only) in individual plethysmographs to various concentrations of sulfur mustard vapor, determined online, using FTIR attached to flow chamber. The LCt 50 and the inhaled LD 50 were calculated at different time points post exposure. Surviving animals were monitored for clinical symptoms, respiratory parameters and body weight changes for up to 30 days. Clinical symptoms were noted at 3 h post exposure, characterized by erythematic and swelling nose with extensive mucous secretion (with or without bleeding). At 6 h post exposure most of the guinea pigs had breathing difficulties, rhonchi and dyspnea and few deaths were noted. These symptoms peaked at 48 h and were noted up to 8 days, associated with few additional deaths. Thereafter, a spontaneous healing was noted, characterized by recovery of respiratory parameters and normal weight gain with almost complete apparent healing within 2 weeks. Histopathological evaluation of lungs and trachea in the surviving GPs at 4 weeks post exposure revealed a dose-dependent residual injury in both lung and trachea expressed by abnormal recovery of the tracheal epithelium concomitant with a dose-dependent increase in cellular volume in the lungs. These abnormal epithelial regeneration and lung remodeling were accompanied with significant changes in protein, LDH, differential cell count and glutathione levels in the bronchoalveolar lavage (BAL). It is suggested that the abnormal epithelial growth and cellular infiltration into the lung as well as the continuous lung inflammation could cause recurrent lung injury similar to that reported for HD exposed human casualties.

  16. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  17. Computational Flow Modeling of Human Upper Airway Breathing

    Science.gov (United States)

    Mylavarapu, Goutham

    Computational modeling of biological systems have gained a lot of interest in biomedical research, in the recent past. This thesis focuses on the application of computational simulations to study airflow dynamics in human upper respiratory tract. With advancements in medical imaging, patient specific geometries of anatomically accurate respiratory tracts can now be reconstructed from Magnetic Resonance Images (MRI) or Computed Tomography (CT) scans, with better and accurate details than traditional cadaver cast models. Computational studies using these individualized geometrical models have advantages of non-invasiveness, ease, minimum patient interaction, improved accuracy over experimental and clinical studies. Numerical simulations can provide detailed flow fields including velocities, flow rates, airway wall pressure, shear stresses, turbulence in an airway. Interpretation of these physical quantities will enable to develop efficient treatment procedures, medical devices, targeted drug delivery etc. The hypothesis for this research is that computational modeling can predict the outcomes of a surgical intervention or a treatment plan prior to its application and will guide the physician in providing better treatment to the patients. In the current work, three different computational approaches Computational Fluid Dynamics (CFD), Flow-Structure Interaction (FSI) and Particle Flow simulations were used to investigate flow in airway geometries. CFD approach assumes airway wall as rigid, and relatively easy to simulate, compared to the more challenging FSI approach, where interactions of airway wall deformations with flow are also accounted. The CFD methodology using different turbulence models is validated against experimental measurements in an airway phantom. Two case-studies using CFD, to quantify a pre and post-operative airway and another, to perform virtual surgery to determine the best possible surgery in a constricted airway is demonstrated. The unsteady

  18. Bovine parainfluenza virus type 3 (PIV3) expressing the respiratory syncytial virus (RSV) attachment and fusion proteins protects hamsters from challenge with human PIV3 and RSV.

    Science.gov (United States)

    Haller, Aurelia A; Mitiku, Misrach; MacPhail, Mia

    2003-08-01

    Parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) are the main causes of ubiquitous acute respiratory diseases of infancy and early childhood, causing 20-25 % of pneumonia and 45-50 % of bronchiolitis in hospitalized children. The primary goal of this study was to create an effective and safe RSV vaccine based on utilizing attenuated bovine PIV3 (bPIV3) as a virus vector backbone. bPIV3 had been evaluated in human clinical trials and was shown to be attenuated and immunogenic in children as young as 2 months of age. The ability of bPIV3 to function as a virus vaccine vector was explored further by introducing the RSV attachment (G) and fusion (F) genes into the bPIV3 RNA genome. The resulting virus, bPIV3/RSV(I), contained an insert of 2900 nt, comprising two translationally competent transcription units. Despite this increase in genetic material, the virus replicated to high titres in Vero cells. This recombinant virus expressed the RSV G and F proteins sufficiently to evoke a protective immune response in hamsters upon challenge with RSV or human PIV3 and to elicit RSV neutralizing and PIV3 haemagglutinin inhibition serum antibodies. In effect, a bivalent vaccine was produced that could protect vaccinees from RSV as well as PIV3. Such a vaccine would vastly reduce the respiratory disease burden, the associated hospitalization costs and, most importantly, decrease morbidity and mortality of infants, immunocompromised individuals and the elderly.

  19. A humanized mouse model of tuberculosis.

    Directory of Open Access Journals (Sweden)

    Veronica E Calderon

    Full Text Available Mycobacterium tuberculosis (M.tb is the second leading infectious cause of death worldwide and the primary cause of death in people living with HIV/AIDS. There are several excellent animal models employed to study tuberculosis (TB, but many have limitations for reproducing human pathology and none are amenable to the direct study of HIV/M.tb co-infection. The humanized mouse has been increasingly employed to explore HIV infection and other pathogens where animal models are limiting. Our goal was to develop a small animal model of M.tb infection using the bone marrow, liver, thymus (BLT humanized mouse. NOD-SCID/γc(null mice were engrafted with human fetal liver and thymus tissue, and supplemented with CD34(+ fetal liver cells. Excellent reconstitution, as measured by expression of the human CD45 pan leukocyte marker by peripheral blood populations, was observed at 12 weeks after engraftment. Human T cells (CD3, CD4, CD8, as well as natural killer cells and monocyte/macrophages were all observed within the human leukocyte (CD45(+ population. Importantly, human T cells were functionally competent as determined by proliferative capacity and effector molecule (e.g. IFN-γ, granulysin, perforin expression in response to positive stimuli. Animals infected intranasally with M.tb had progressive bacterial infection in the lung and dissemination to spleen and liver from 2-8 weeks post infection. Sites of infection in the lung were characterized by the formation of organized granulomatous lesions, caseous necrosis, bronchial obstruction, and crystallization of cholesterol deposits. Human T cells were distributed throughout the lung, liver, and spleen at sites of inflammation and bacterial growth and were organized to the periphery of granulomas. These preliminary results demonstrate the potential to use the humanized mouse as a model of experimental TB.

  20. Knowledge Brokering: An Innovative Model for Supporting Evidence-Informed Practice in Respiratory Care

    Directory of Open Access Journals (Sweden)

    Alison M Hoens

    2013-01-01

    Full Text Available The process of adopting research findings in the clinical setting is challenging, regardless of the area of practice. One strategy to facilitate this process is the use of knowledge brokering. Knowledge brokers (KBs are individuals who work to bridge the gap between researchers and knowledge users. In the health care setting, KBs work closely with clinicians to facilitate enhanced uptake of research findings into clinical practice. They also work with researchers to ensure research findings are translatable and meaningful to clinical practice. The present article discusses a KB’s role in a respiratory care setting. Working closely with both researchers and clinicians, the KB has led teams in the process of conceptualizing, developing, testing, disseminating and evaluating several projects related to respiratory care, including projects related to mobility in critical care settings and acute exacerbations of chronic obstructive pulmonary disease; inspiratory muscle training; and the use of incentive spirometry in postsurgical populations. The KB role has provided an important communication link between researcher and knowledge user that has facilitated evidence-informed practice to improve patient care.

  1. A statistical model of future human actions

    International Nuclear Information System (INIS)

    Woo, G.

    1992-02-01

    A critical review has been carried out of models of future human actions during the long term post-closure period of a radioactive waste repository. Various Markov models have been considered as alternatives to the standard Poisson model, and the problems of parameterisation have been addressed. Where the simplistic Poisson model unduly exaggerates the intrusion risk, some form of Markov model may have to be introduced. This situation may well arise for shallow repositories, but it is less likely for deep repositories. Recommendations are made for a practical implementation of a computer based model and its associated database. (Author)

  2. Material Models for the Human Torso Finite Element Model

    Science.gov (United States)

    2018-04-04

    ARL-TR-8338 ● Apr 2018 US Army Research Laboratory Material Models for the Human Torso Finite Element Model by Carolyn E...longer needed. Do not return it to the originator. ARL-TR-8338 ● Apr 2018 US Army Research Laboratory Material Models for the...Weapons and Materials Research Directorate, ARL Approved for public release; distribution is unlimited. ii REPORT

  3. Modeling human learning involved in car driving

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1994-01-01

    In this paper, car driving is considered at the level of human tracking and maneuvering in the context of other traffic. A model analysis revealed the most salient features determining driving performance and safety. Learning car driving is modelled based on a system theoretical approach and based

  4. A Model of the Human Eye

    Science.gov (United States)

    Colicchia, G.; Wiesner, H.; Waltner, C.; Zollman, D.

    2008-01-01

    We describe a model of the human eye that incorporates a variable converging lens. The model can be easily constructed by students with low-cost materials. It shows in a comprehensible way the functionality of the eye's optical system. Images of near and far objects can be focused. Also, the defects of near and farsighted eyes can be demonstrated.

  5. Mathematical human body modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling of the human body is widely used for automotive crash safety research and design. Simulations have contributed to a reduction of injury numbers by optimisation of vehicle structures and restraint systems. Currently such simulations are largely performed using occupant models

  6. Dependence of subject-specific parameters for a fast helical CT respiratory motion model on breathing rate: an animal study

    Science.gov (United States)

    O'Connell, Dylan; Thomas, David H.; Lamb, James M.; Lewis, John H.; Dou, Tai; Sieren, Jered P.; Saylor, Melissa; Hofmann, Christian; Hoffman, Eric A.; Lee, Percy P.; Low, Daniel A.

    2018-02-01

    To determine if the parameters relating lung tissue displacement to a breathing surrogate signal in a previously published respiratory motion model vary with the rate of breathing during image acquisition. An anesthetized pig was imaged using multiple fast helical scans to sample the breathing cycle with simultaneous surrogate monitoring. Three datasets were collected while the animal was mechanically ventilated with different respiratory rates: 12 bpm (breaths per minute), 17 bpm, and 24 bpm. Three sets of motion model parameters describing the correspondences between surrogate signals and tissue displacements were determined. The model error was calculated individually for each dataset, as well asfor pairs of parameters and surrogate signals from different experiments. The values of one model parameter, a vector field denoted α which related tissue displacement to surrogate amplitude, determined for each experiment were compared. The mean model error of the three datasets was 1.00  ±  0.36 mm with a 95th percentile value of 1.69 mm. The mean error computed from all combinations of parameters and surrogate signals from different datasets was 1.14  ±  0.42 mm with a 95th percentile of 1.95 mm. The mean difference in α over all pairs of experiments was 4.7%  ±  5.4%, and the 95th percentile was 16.8%. The mean angle between pairs of α was 5.0  ±  4.0 degrees, with a 95th percentile of 13.2 mm. The motion model parameters were largely unaffected by changes in the breathing rate during image acquisition. The mean error associated with mismatched sets of parameters and surrogate signals was 0.14 mm greater than the error achieved when using parameters and surrogate signals acquired with the same breathing rate, while maximum respiratory motion was 23.23 mm on average.

  7. Mathematical models of human african trypanosomiasis epidemiology.

    Science.gov (United States)

    Rock, Kat S; Stone, Chris M; Hastings, Ian M; Keeling, Matt J; Torr, Steve J; Chitnis, Nakul

    2015-03-01

    Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 5D respiratory motion model based image reconstruction algorithm for 4D cone-beam computed tomography

    Science.gov (United States)

    Liu, Jiulong; Zhang, Xue; Zhang, Xiaoqun; Zhao, Hongkai; Gao, Yu; Thomas, David; Low, Daniel A.; Gao, Hao

    2015-11-01

    4D cone-beam computed tomography (4DCBCT) reconstructs a temporal sequence of CBCT images for the purpose of motion management or 4D treatment in radiotherapy. However the image reconstruction often involves the binning of projection data to each temporal phase, and therefore suffers from deteriorated image quality due to inaccurate or uneven binning in phase, e.g., under the non-periodic breathing. A 5D model has been developed as an accurate model of (periodic and non-periodic) respiratory motion. That is, given the measurements of breathing amplitude and its time derivative, the 5D model parametrizes the respiratory motion by three time-independent variables, i.e., one reference image and two vector fields. In this work we aim to develop a new 4DCBCT reconstruction method based on 5D model. Instead of reconstructing a temporal sequence of images after the projection binning, the new method reconstructs time-independent reference image and vector fields with no requirement of binning. The image reconstruction is formulated as a optimization problem with total-variation regularization on both reference image and vector fields, and the problem is solved by the proximal alternating minimization algorithm, during which the split Bregman method is used to reconstruct the reference image, and the Chambolle's duality-based algorithm is used to reconstruct the vector fields. The convergence analysis of the proposed algorithm is provided for this nonconvex problem. Validated by the simulation studies, the new method has significantly improved image reconstruction accuracy due to no binning and reduced number of unknowns via the use of the 5D model.

  9. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  10. Respiratory alkalosis

    Science.gov (United States)

    ... a condition marked by a low level of carbon dioxide in the blood due to breathing excessively. ... aimed at the condition that causes respiratory alkalosis. Breathing ... dioxide -- sometimes helps reduce symptoms when anxiety is the ...

  11. The Virome and Its Major Component, Anellovirus, a Convoluted System Molding Human Immune Defenses and Possibly Affecting the Development of Asthma and Respiratory Diseases in Childhood

    Directory of Open Access Journals (Sweden)

    Giulia Freer

    2018-04-01

    Full Text Available The microbiome, a thriving and complex microbial community colonizing the human body, has a broad impact on human health. Colonization is a continuous process that starts very early in life and occurs thanks to shrewd strategies microbes have evolved to tackle a convoluted array of anatomical, physiological, and functional barriers of the human body. Cumulative evidence shows that viruses are part of the microbiome. This part, called virome, has a dynamic composition that reflects what we eat, how and where we live, what we do, our genetic background, and other unpredictable variables. Thus, the virome plays a chief role in shaping innate and adaptive host immune defenses. Imbalance of normal microbial flora is thought to trigger or exacerbate many acute and chronic disorders. A compelling example can be found in the respiratory apparatus, where early-life viral infections are major determinants for the development of allergic diseases, like asthma, and other non-transmissible diseases. In this review, we focus on the virome and, particularly, on Anelloviridae, a recently discovered virus family. Anelloviruses are major components of the virome, present in most, if not all, human beings, where they are acquired early in life and replicate persistently without causing apparent disease. We will discuss how modulation of innate and adaptive immune systems by Anelloviruses can influence the development of respiratory diseases in childhood and provide evidence for the use of Anelloviruses as useful and practical molecular markers to monitor inflammatory processes and immune system competence.

  12. Impact of Cardiopulmonary Bypass on Respiratory Mucociliary Function in an Experimental Porcine Model.

    Directory of Open Access Journals (Sweden)

    Rodrigo Sánchez-Véliz

    Full Text Available The impact of cardiac surgery using cardiopulmonary bypass (CPB on the respiratory mucociliary function is unknown. This study evaluated the effects of CPB and interruption of mechanical ventilation on the respiratory mucociliary system.Twenty-two pigs were randomly assigned to the control (n = 10 or CPB group (n = 12. After the induction of anesthesia, a tracheostomy was performed, and tracheal tissue samples were excised (T0 from both groups. All animals underwent thoracotomy. In the CPB group, an aorto-bicaval CPB was installed and maintained for 90 minutes. During the CPB, mechanical ventilation was interrupted, and the tracheal tube was disconnected. A second tracheal tissue sample was obtained 180 minutes after the tracheostomy (T180. Mucus samples were collected from the trachea using a bronchoscope at T0, T90 and T180. Ciliary beat frequency (CBF and in situ mucociliary transport (MCT were studied in ex vivo tracheal epithelium. Mucus viscosity (MV was assessed using a cone-plate viscometer. Qualitative tracheal histological analysis was performed at T180 tissue samples.CBF decreased in the CPB group (13.1 ± 1.9 Hz vs. 11.1 ± 2.1 Hz, p < 0.05 but not in the control group (13.1 ± 1 Hz vs. 13 ± 2.9 Hz. At T90, viscosity was increased in the CPB group compared to the control (p < 0.05. No significant differences were observed in in situ MCT. Tracheal histology in the CPB group showed areas of ciliated epithelium loss, submucosal edema and infiltration of inflammatory cells.CPB acutely contributed to alterations in tracheal mucocilliary function.

  13. Pharmacological Effects of Lactuca serriola L. in Experimental Model of Gastrointestinal, Respiratory, and Vascular Ailments

    Directory of Open Access Journals (Sweden)

    Khalid Hussain Janbaz

    2013-01-01

    Full Text Available Lactuca serriola L. has traditionally been used in folkloric medicine to manage respiratory, gastrointestinal, and multiple other ailments. The present study was undertaken to explore the effect of methanol extract of L. serriola on isolated rabbit tissue preparations, that is, jejunum, trachea, and aorta in an attempt to validate its folkloric use in traditional medicine for gastrointestinal, respiratory, and vascular ailments. The application of the methanol extract to isolated rabbit jejunum preparations exhibited concentration-dependent spasmogenic effect (0.03 to 3.0 mg/mL, but interestingly further increase in concentration (5.0 mg/mL resulted in complete spasmolytic effect. The pretreatment of the tissue preparations with atropine (0.1 μM caused the suppression of the contractile response. Moreover, the same extract also caused relaxation of K+-(80 mM induced spastic contractions of isolated rabbit jejunum preparations (5.0 mg/mL and shifted the Ca++ dose response curves towards right at concentration range of 0.3–1.0 mg/mL. Similarly, the extract application to isolated rabbit tracheal preparations relaxed the carbachol-(1 μM induced (0.3–1.0 mg/mL as well as K+-(80 mM induced contractions (3.0 mg/mL. Furthermore, it relaxed the phenylephrine (1 μM-induced contractions in isolated rabbit aorta preparations (3.0 mg/mL and K+ (80 mM-induced contractions (1.0 mg/mL. These effects were found comparable to that of dicyclomine, as an antagonist of muscarinic receptors as well as a possible Ca++ channel blocker. The previously mentioned findings may partially justify the folkloric use of Lactuca serriola in the management of conditions pertaining to spasm of intestine, bronchioles, and vasculature.

  14. Comparative studies on virus detection in acute respiratory diseases in humans by means of RIA and cultivation

    International Nuclear Information System (INIS)

    Ehrlicher, L.

    1982-01-01

    In winter 1981, 146 patients with an acute respiratory infection were examined. Nasopharyngeal specimens were obtained by intranasal catheter. Comparative investigations were performed by cultivation in tissue culture and by a four-layer radioimmunoassay. In the radioimmunoassay, polystyrene beads were used as the solid phase, ginea pig antivirus immunoglobulins as the captive antibodies, rabbit anti-virus immunoglobulins as the secondary antibodies and 125 I-labelled sheep anti-rabbit immunoglobulins were used as the indicator antibodies. The radioimmunoassay was developed for the detection of adenovirus, respiratory syncytial virus, influenza A and B virus and parainfluenza type 1, type 2 and type 3 virus. Tissue culture seems to be more sensitive for detection of adenovirus and influenza A virus, though some infections with influenza A virus could only be diagnosed by the radioimmunoassay. In other cases (respiratory syncytial virus, influenza B virus) antigen detection by radioimmunoassay is more efficient. Presently the combination of both antigen-detection-systems still is the optimal diagnostic procedure for detecting virus infections of the respiratory tract. (orig./MG) [de

  15. Airway remodeling in a mouse asthma model assessed by in-vivo respiratory-gated micro-computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lederlin, Mathieu; Montaudon, Michel [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); Ozier, Annaig; Begueret, Hugues; Ousova, Olga; Marthan, Roger; Berger, Patrick [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); Laurent, Francois [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); CHU de Bordeaux, Hopital du Haut-Leveque, Hopital Cardiologique, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France)

    2010-01-15

    The aim of our study was to evaluate the feasibility of non-invasive respiratory-gated micro-computed tomography (micro-CT) for assessment of airway remodelling in a mouse asthma model. Six female BALB/c mice were challenged intranasally with ovalbumin. A control group of six mice received saline inhalation. All mice underwent plethysmographic study and micro-CT. For each mouse, peribronchial attenuation values of 12 bronchi were measured, from which a peribronchial density index (PBDI) was computed. Mice were then sacrificed and lungs examined histologically. Final analysis involved 10 out of 12 mice. Agreement of measurements across observers and over time was very good (intraclass correlation coefficients: 0.94-0.98). There was a significant difference in PBDI between asthmatic and control mice (-210 vs. -338.9 HU, P=0.008). PBDI values were correlated to bronchial muscle area (r=0.72, P=0.018). This study shows that respiratory-gated micro-CT may allow non-invasive monitoring of bronchial remodelling in asthmatic mice and evaluation of innovative treatment effects. (orig.)

  16. Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays.

    Directory of Open Access Journals (Sweden)

    Roujian Lu

    Full Text Available BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV and human bocavirus (HBoV. 157 of the 981 (16.0% nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%, OC43 (42 cases, 4.3%, HKU1 (16 cases, 1.6% and NL63 (11 cases, 1.1%. HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003, and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03. 48 of 157(30.57% HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu A were the most common viruses detected (more than 35% in HCoV co-infections. Respiratory syncytial virus (RSV, human parainfluenza virus (PIV and HBoV were detected in very low rate (less than 1% among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

  17. Identification of walking human model using agent-based modelling

    Science.gov (United States)

    Shahabpoor, Erfan; Pavic, Aleksandar; Racic, Vitomir

    2018-03-01

    The interaction of walking people with large vibrating structures, such as footbridges and floors, in the vertical direction is an important yet challenging phenomenon to describe mathematically. Several different models have been proposed in the literature to simulate interaction of stationary people with vibrating structures. However, the research on moving (walking) human models, explicitly identified for vibration serviceability assessment of civil structures, is still sparse. In this study, the results of a comprehensive set of FRF-based modal tests were used, in which, over a hundred test subjects walked in different group sizes and walking patterns on a test structure. An agent-based model was used to simulate discrete traffic-structure interactions. The occupied structure modal parameters found in tests were used to identify the parameters of the walking individual's single-degree-of-freedom (SDOF) mass-spring-damper model using 'reverse engineering' methodology. The analysis of the results suggested that the normal distribution with the average of μ = 2.85Hz and standard deviation of σ = 0.34Hz can describe human SDOF model natural frequency. Similarly, the normal distribution with μ = 0.295 and σ = 0.047 can describe the human model damping ratio. Compared to the previous studies, the agent-based modelling methodology proposed in this paper offers significant flexibility in simulating multi-pedestrian walking traffics, external forces and simulating different mechanisms of human-structure and human-environment interaction at the same time.

  18. Comparison of artificial neural network (ANN) and partial least squares (PLS) regression models for predicting respiratory ventilation: an exploratory study.

    Science.gov (United States)

    Lin, Ming-I Brandon; Groves, William A; Freivalds, Andris; Lee, Eun Gyung; Harper, Martin

    2012-05-01

    The objective of this study was to assess the potential for using artificial neural networks (ANN) to predict inspired minute ventilation (V(I)) during exercise activities. Six physiological/kinematic measurements obtained from a portable ambulatory monitoring system, along with individual's anthropometric and demographic characteristics, were employed as input variables to develop and optimize the ANN configuration with respect to reference values simultaneously measured using a pneumotachograph (PT). The generalization ability of the resulting two-hidden-layer ANN model was compared with a linear predictive model developed through partial least squares (PLS) regression, as well as other V(I) predictive models proposed in the literature. Using an independent dataset recorded from nine 80-min step tests, the results showed that the ANN-estimated V(I) was highly correlated (R(2) = 0.88) with V(I) measured by the PT, with a mean difference of approximately 0.9%. In contrast, the PLS and other regression-based models resulted in larger average errors ranging from 7 to 34%. In addition, the ANN model yielded estimates of cumulative total volume that were on average within 1% of reference PT measurements. Compared with established statistical methods, the proposed ANN model demonstrates the potential to provide improved prediction of respiratory ventilation in workplace applications for which the use of traditional laboratory-based instruments is not feasible. Further research should be conducted to investigate the performance of ANNs for different types of physical activity in larger and more varied worker populations.

  19. [How I manage respiratory syncytial virus, human herpesvirus 6 and adenovirus reactivation or infection after allogeneic stem cell transplantation: a report of the SFGM-TC].

    Science.gov (United States)

    Deconinck, E; Dalle, J-H; Berceanu, A; Chevallier, P; Duléry, R; Garnier, A; Huynh, A; Labussière-Wallet, H; Nguyen Quoc, S; Dewilde, A; Ramon, P; Yakoub-Agha, I

    2013-08-01

    In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of virus respiratory syncytial virus (RSV), human herpes virus 6 (HHV6) or adenovirus allogeneic Stem Cell Transplantation. Copyright © 2013. Published by Elsevier SAS.

  20. Analisis Model Pengukuran Human Capital dalam Organisasi

    Directory of Open Access Journals (Sweden)

    Cecep Hidayat

    2013-11-01

    Full Text Available Measurement of human capital is not an easy to do because it is dynamic and always changing in accordance with the changing circumstances. Determination of dimensions and indicators of measurement needs to consider various factors such as situations and also the research scopes. This article has objectives to review the concepts, dimensions and measurement models of human capital. The research method used was literature study with a major reference source from current journal articles that discuss the measurement of human capital. Results of the study showed that basically the definition set forth in any dimension containing either explicitly or implicitly. In addition, the result indicated that there are three main categories of equality among researchers regarding the definition of human capital which emphasizes on: economic value/productivity, education, and abilities/competencies. The results also showed that the use of definitions, dimensions, and indicators for measurement of human capital depends on the situation, the scope of research, and the size of the organization. The conclusion of the study indicated that the measurement model and determination of dimensions and indicators of human capital measurement will determine the effectiveness of the measurement, and will have an impact on organizational performance.

  1. Modeling the exergy behavior of human body

    International Nuclear Information System (INIS)

    Keutenedjian Mady, Carlos Eduardo; Silva Ferreira, Maurício; Itizo Yanagihara, Jurandir; Hilário Nascimento Saldiva, Paulo; Oliveira Junior, Silvio de

    2012-01-01

    Exergy analysis is applied to assess the energy conversion processes that take place in the human body, aiming at developing indicators of health and performance based on the concepts of exergy destroyed rate and exergy efficiency. The thermal behavior of the human body is simulated by a model composed of 15 cylinders with elliptical cross section representing: head, neck, trunk, arms, forearms, hands, thighs, legs, and feet. For each, a combination of tissues is considered. The energy equation is solved for each cylinder, being possible to obtain transitory response from the body due to a variation in environmental conditions. With this model, it is possible to obtain heat and mass flow rates to the environment due to radiation, convection, evaporation and respiration. The exergy balances provide the exergy variation due to heat and mass exchange over the body, and the exergy variation over time for each compartments tissue and blood, the sum of which leads to the total variation of the body. Results indicate that exergy destroyed and exergy efficiency decrease over lifespan and the human body is more efficient and destroys less exergy in lower relative humidities and higher temperatures. -- Highlights: ► In this article it is indicated an overview of the human thermal model. ► It is performed the energy and exergy analysis of the human body. ► Exergy destruction and exergy efficiency decreases with lifespan. ► Exergy destruction and exergy efficiency are a function of environmental conditions.

  2. Modeling of indoor 222Rn distribution in ventilated room and resulting radiation doses measured in the respiratory tract

    Directory of Open Access Journals (Sweden)

    R. Rabi

    2017-07-01

    Full Text Available Most of radiation hazard of indoor radon is largely due to the radon progenies, which are inhaled and deposited in the human respiratory tract. It is therefore important to understanding the distribution of radon and their progeny in indoor environment helps in calculating the inhalation doses due to them. This paper focuses on effects of exhalation from different sources (wall, floor and ceiling and the ventilation profile on distribution of the concentrations of radon and their progeny indoor. The radon exhalation rate from walls, floor and ceiling, and ventilation rate were measured as a part of this study and are used as input in Finite Volume Method (FVM simulation. The findings show that the radon concentration which is distributed in a non-homogeneous way in the room is due to the difference in the radon concentration of different sources (wall, floor and ceiling. Moreover, the radon concentration is much larger near walls, and decreases in the middle of the room because of the effect of air velocity. It has also been found that the distributions of unattached and attached fraction of 218Po, 214Pb and 214Po radionuclides are similar to that of 222Rn. In addition, equilibrium fraction F and the unattached fraction ( fj  of 218Po, 214Pb and 214Po radionuclides for different values of the attachment rate were evaluated. The committed equivalent doses due to 218Po and 214Po radon short-lived progeny were evaluated in different tissues of the respiratory tract of workers from the inhalation of indoor air.

  3. Models of the Human in Tantric Hinduism

    DEFF Research Database (Denmark)

    Olesen, Bjarne Wernicke; Flood, Gavin

    2019-01-01

    This research project explores the origins, developments and transformations of yogic models of the human (e.g. kuṇḍalinī yoga, the cakra system and ritual sex) in the tantric goddess traditions or what might be called Śāktism of medieval India. These Śākta models of esoteric anatomy originating...... in medieval ascetic traditions became highly influential in South Asia and were popularized in the West....

  4. Measurement of the deposited activity of the short-lived radon progeny in the human respiratory tract

    International Nuclear Information System (INIS)

    Vezzu, G.; Butterweck-Dempewolf, G.; Schuler, C.

    1998-01-01

    Volunteers were exposed in the radon chamber at Paul Scherrer Institut to an atmosphere enriched with highly unattached radon progeny. The deposited radon progeny activity in the respiratory tract of the volunteers was determined using a low level in-vivo counter. The detector arrangement and its calibration for the measurement of deposited radon progeny activity is described and the results for a mouth and a nose breathing volunteer are presented. For the nose breathing volunteer 55% of the deposited radon progeny activity was located in the head and the remaining 45% in the chest whereas for the mouth breathing volunteer 25% was located in the head and the remaining 75% in the chest. A mean clearance half-life for the deposited radon progeny from the respiratory tract of (2±1) h was obtained from the analyses of the temporal behaviour of the deposited radon progeny activity in the head. (orig.)

  5. Are animal models predictive for humans?

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2009-01-01

    Full Text Available Abstract It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics.

  6. [Primate models of human viral hepatitis].

    Science.gov (United States)

    Poleshchuk, V F; Mikhaĭlov, M I; Zamiatina, N A

    2006-01-01

    The paper summarizes the updates available in the literature and the authors' own data on the etiology of hepatitis, its models, and experimental studies on susceptible simian types. A comparative analysis of the etiological agents--the causative agents of simian and human hepatitis will give a better insight into the evolution of its viruses.

  7. Human driven transitions in complex model ecosystems

    Science.gov (United States)

    Harfoot, Mike; Newbold, Tim; Tittinsor, Derek; Purves, Drew

    2015-04-01

    Human activities have been observed to be impacting ecosystems across the globe, leading to reduced ecosystem functioning, altered trophic and biomass structure and ultimately ecosystem collapse. Previous attempts to understand global human impacts on ecosystems have usually relied on statistical models, which do not explicitly model the processes underlying the functioning of ecosystems, represent only a small proportion of organisms and do not adequately capture complex non-linear and dynamic responses of ecosystems to perturbations. We use a mechanistic ecosystem model (1), which simulates the underlying processes structuring ecosystems and can thus capture complex and dynamic interactions, to investigate boundaries of complex ecosystems to human perturbation. We explore several drivers including human appropriation of net primary production and harvesting of animal biomass. We also present an analysis of the key interactions between biotic, societal and abiotic earth system components, considering why and how we might think about these couplings. References: M. B. J. Harfoot et al., Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model., PLoS Biol. 12, e1001841 (2014).

  8. Quality assessment of human behavior models

    NARCIS (Netherlands)

    Doesburg, W.A. van

    2007-01-01

    Accurate and efficient models of human behavior offer great potential in military and crisis management applications. However, little attention has been given to the man ner in which it can be determined if this potential is actually realized. In this study a quality assessment approach that

  9. Future of human models for crash analysis

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    In the crash safety field mathematical models can be applied in practically all area's of research and development including: reconstruction of actual accidents, design (CAD) of the crash response of vehicles, safety devices and roadside facilities and in support of human impact biomechanical

  10. Arteriovenous extracorporeal lung assist allows for maximization of oscillatory frequencies: a large-animal model of respiratory distress

    Directory of Open Access Journals (Sweden)

    Kranke Peter

    2008-11-01

    Full Text Available Abstract Background Although the minimization of the applied tidal volume (VT during high-frequency oscillatory ventilation (HFOV reduces the risk of alveolar shear stress, it can also result in insufficient CO2-elimination with severe respiratory acidosis. We hypothesized that in a model of acute respiratory distress (ARDS the application of high oscillatory frequencies requires the combination of HFOV with arteriovenous extracorporeal lung assist (av-ECLA in order to maintain or reestablish normocapnia. Methods After induction of ARDS in eight female pigs (56.5 ± 4.4 kg, a recruitment manoeuvre was performed and intratracheal mean airway pressure (mPaw was adjusted 3 cmH2O above the lower inflection point (Plow of the pressure-volume curve. All animals were ventilated with oscillatory frequencies ranging from 3–15 Hz. The pressure amplitude was fixed at 60 cmH2O. At each frequency gas exchange and hemodynamic measurements were obtained with a clamped and de-clamped av-ECLA. Whenever the av-ECLA was de-clamped, the oxygen sweep gas flow through the membrane lung was adjusted aiming at normocapnia. Results Lung recruitment and adjustment of the mPaw above Plow resulted in a significant improvement of oxygenation (p Conclusion In this animal model of ARDS, maximization of oscillatory frequencies with subsequent minimization of VT leads to hypercapnia that can only be reversed by adding av-ECLA. When combined with a recruitment strategy, these high frequencies do not impair oxygenation

  11. Arteriovenous Extracorporeal Lung Assist Allows For Maximization Of Oscillatory Frequencies: A Large-animal Model Of Respiratory Distress.

    Science.gov (United States)

    Muellenbach, Ralf M; Kuestermann, Julian; Kredel, Markus; Johannes, Amélie; Wolfsteiner, Ulrike; Schuster, Frank; Wunder, Christian; Kranke, Peter; Roewer, Norbert; Brederlau, Jörg

    2008-11-14

    Although the minimization of the applied tidal volume (VT) during high-frequency oscillatory ventilation (HFOV) reduces the risk of alveolar shear stress, it can also result in insufficient CO₂-elimination with severe respiratory acidosis. We hypothesized that in a model of acute respiratory distress (ARDS) the application of high oscillatory frequencies requires the combination of HFOV with arteriovenous extracorporeal lung assist (av-ECLA) in order to maintain or reestablish normocapnia. After induction of ARDS in eight female pigs (56.5 ± 4.4 kg), a recruitment manoeuvre was performed and intratracheal mean airway pressure (mPaw) was adjusted 3 cmH₂O above the lower inflection point (Plow) of the pressure-volume curve. All animals were ventilated with oscillatory frequencies ranging from 3-15 Hz. The pressure amplitude was fixed at 60 cmH₂O. At each frequency gas exchange and hemodynamic measurements were obtained with a clamped and de-clamped av-ECLA. Whenever the av-ECLA was de-clamped, the oxygen sweep gas flow through the membrane lung was adjusted aiming at normocapnia. Lung recruitment and adjustment of the mPaw above Plow resulted in a significant improvement of oxygenation (p < 0.05). Compared to lung injury, oxygenation remained significantly improved with rising frequencies (p < 0.05). Normocapnia during HFOV was only maintained with the addition of av-ECLA during frequencies of 9 Hz and above. In this animal model of ARDS, maximization of oscillatory frequencies with subsequent minimization of VT leads to hypercapnia that can only be reversed by adding av-ECLA. When combined with a recruitment strategy, these high frequencies do not impair oxygenation.

  12. Optical models of the human eye.

    Science.gov (United States)

    Atchison, David A; Thibos, Larry N

    2016-03-01

    Optical models of the human eye have been used in visual science for purposes such as providing a framework for explaining optical phenomena in vision, for predicting how refraction and aberrations are affected by change in ocular biometry and as computational tools for exploring the limitations imposed on vision by the optical system of the eye. We address the issue of what is understood by optical model eyes, discussing the 'encyclopaedia' and 'toy train' approaches to modelling. An extensive list of purposes of models is provided. We discuss many of the theoretical types of optical models (also schematic eyes) of varying anatomical accuracy, including single, three and four refracting surface variants. We cover the models with lens structure in the form of nested shells and gradient index. Many optical eye models give accurate predictions only for small angles and small fields of view. If aberrations and image quality are important to consider, such 'paraxial' model eyes must be replaced by 'finite model' eyes incorporating features such as aspheric surfaces, tilts and decentrations, wavelength-dependent media and curved retinas. Many optical model eyes are population averages and must become adaptable to account for age, gender, ethnicity, refractive error and accommodation. They can also be customised for the individual when extensive ocular biometry and optical performance data are available. We consider which optical model should be used for a particular purpose, adhering to the principle that the best model is the simplest fit for the task. We provide a glimpse into the future of optical models of the human eye. This review is interwoven with historical developments, highlighting the important people who have contributed so richly to our understanding of visual optics. © 2016 The Authors. Clinical and Experimental Optometry © 2016 Optometry Australia.

  13. Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation

    Directory of Open Access Journals (Sweden)

    Emily Medlin Martin

    2017-09-01

    Full Text Available In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed. One potential neutrophil-targeting therapeutic is the PGE1 analog, misoprostol. Misoprostol is a gastroprotectant that induces intracellular formation of the secondary messenger molecule cyclic AMP (cAMP, which has been shown to have anti-inflammatory effects on neutrophils. Misoprostol is currently used in horses to treat NSAID-induced gastrointestinal injury; however, its effects on equine neutrophils have not been determined. We hypothesized that treatment of equine neutrophils with misoprostol would inhibit equine neutrophil adhesion, migration, and ROS production, in vitro. We tested this hypothesis using isolated equine peripheral blood neutrophils collected from 12 healthy adult teaching/research horses of mixed breed and gender. The effect of misoprostol treatment on adhesion, migration, and respiratory burst of equine neutrophils was evaluated via fluorescence-based adhesion and chemotaxis assays, and luminol-enhanced chemiluminescence, respectively. Neutrophils were pretreated with varying concentrations of misoprostol, vehicle, or appropriate functional inhibitory controls prior to stimulation with LTB4, CXCL8, PAF, lipopolysaccharide (LPS or immune complex (IC. This study revealed that misoprostol pretreatment significantly inhibited LTB4-induced adhesion, LTB4-, CXCL8-, and PAF-induced chemotaxis, and LPS-, IC-, and PMA-induced ROS production in a concentration-dependent manner. This data indicate that

  14. Activity of Ingavirin (6-[2-(1H-Imidazol-4-ylethylamino]-5-oxo-hexanoic Acid Against Human Respiratory Viruses in in Vivo Experiments

    Directory of Open Access Journals (Sweden)

    Oleg I. Kiselev

    2011-11-01

    Full Text Available Respiratory viral infections constitute the most frequent reason for medical consultations in the World. They can be associated with a wide range of clinical manifestations ranging from self-limited upper respiratory tract infections to more devastating conditions such as pneumonia. In particular, in serious cases influenza A leads to pneumonia, which is particularly fatal in patients with cardiopulmonary diseases, obesity, young children and the elderly. In the present study, we show a protective effect of the low-molecular weight compound Ingavirin (6-[2-(1H-imidazol-4-ylethylamino]-5-oxohexanoic acid against influenza A (H1N1 virus, human parainfluenza virus and human adenovirus infections in animals. Mortality, weight loss, infectious titer of the virus in tissues and tissue morphology were monitored in the experimental groups of animals. The protective action of Ingavirin was observed as a reduction of infectious titer of the virus in the lung tissue, prolongation of the life of the infected animals, normalization of weight dynamics throughout the course of the disease, lowering of mortality of treated animals compared to a placebo control and normalization of tissue structure. In case of influenza virus infection, the protective activity of Ingavirin was similar to that of the reference compound Tamiflu. Based on the results obtained, Ingavirin should be considered as an important part of anti-viral prophylaxis and therapy.

  15. Intraindividual comparison of image quality using retrospective and prospective respiratory gating for the acquisition of thin sliced four dimensional multidetector CT of the thorax in a porcine model.

    Science.gov (United States)

    Behzadi, Cyrus; Groth, Michael; Henes, Frank Oliver; Schwarz, Dorothee; Deibele, André; Begemann, Philipp G C; Adam, Gerhard; Regier, Marc

    2015-01-01

    To intraindividually compare image quality and anatomical depiction of the lung and mediastinum using retrospective and prospective respiratory gating techniques for the acquisition of 4D-multidetector computed tomography (MDCT) of the chest in a porcine model. Twelve trachealy intubated domestic pigs underwent 64-row MDCT of the thorax. For retrospective and prospective gating the automated respiratory frequency was adjusted to 10, 14, 18, and 22 respiratory cycles per minute. Further, free breathing MDCT scans of the lung were performed at the same respiratory settings. A breathhold scan was acquired which served as the reference standard. Three reviewers independently analyzed the MDCT data applying a 4-point-grading scale regarding the degree of artifacts observed and anatomical depiction (1, excellent, no artifacts; 4, nondiagnostic due to severe artifacts). For statistical analysis the Wilcoxon matched pairs and Chi-square test were used. Breathhold imaging allowed for the highest image quality (mean value: trachea, 1.00; bronchi, 1.10; lung parenchyma, 1.08; diaphragm, 1.00; pericardium, 1.80). Retrospective gating proved to be of superior image quality compared to prospective gating for all respiratory frequencies. With the respiratory frequency set to 14/min retrospective gating even enabled an identical image quality score as at breathhold. Performing image acquisition during continuous breathing lead to a severe decrease in image quality. High image quality can be acquired using respiratory gating techniques for 4D-MDCT of the thorax. Retrospective is superior to prospective gating and can be of an equivalent image quality as standard breathhold imaging, but at the cost of a significantly higher radiation dose.

  16. Modeling Operations Costs for Human Exploration Architectures

    Science.gov (United States)

    Shishko, Robert

    2013-01-01

    Operations and support (O&S) costs for human spaceflight have not received the same attention in the cost estimating community as have development costs. This is unfortunate as O&S costs typically comprise a majority of life-cycle costs (LCC) in such programs as the International Space Station (ISS) and the now-cancelled Constellation Program. Recognizing this, the Constellation Program and NASA HQs supported the development of an O&S cost model specifically for human spaceflight. This model, known as the Exploration Architectures Operations Cost Model (ExAOCM), provided the operations cost estimates for a variety of alternative human missions to the moon, Mars, and Near-Earth Objects (NEOs) in architectural studies. ExAOCM is philosophically based on the DoD Architecture Framework (DoDAF) concepts of operational nodes, systems, operational functions, and milestones. This paper presents some of the historical background surrounding the development of the model, and discusses the underlying structure, its unusual user interface, and lastly, previous examples of its use in the aforementioned architectural studies.

  17. Computer Modeling of Human Delta Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Tatyana Dzimbova

    2013-04-01

    Full Text Available The development of selective agonists of δ-opioid receptor as well as the model of interaction of ligands with this receptor is the subjects of increased interest. In the absence of crystal structures of opioid receptors, 3D homology models with different templates have been reported in the literature. The problem is that these models are not available for widespread use. The aims of our study are: (1 to choose within recently published crystallographic structures templates for homology modeling of the human δ-opioid receptor (DOR; (2 to evaluate the models with different computational tools; and (3 to precise the most reliable model basing on correlation between docking data and in vitro bioassay results. The enkephalin analogues, as ligands used in this study, were previously synthesized by our group and their biological activity was evaluated. Several models of DOR were generated using different templates. All these models were evaluated by PROCHECK and MolProbity and relationship between docking data and in vitro results was determined. The best correlations received for the tested models of DOR were found between efficacy (erel of the compounds, calculated from in vitro experiments and Fitness scoring function from docking studies. New model of DOR was generated and evaluated by different approaches. This model has good GA341 value (0.99 from MODELLER, good values from PROCHECK (92.6% of most favored regions and MolProbity (99.5% of favored regions. Scoring function correlates (Pearson r = -0.7368, p-value = 0.0097 with erel of a series of enkephalin analogues, calculated from in vitro experiments. So, this investigation allows suggesting a reliable model of DOR. Newly generated model of DOR receptor could be used further for in silico experiments and it will give possibility for faster and more correct design of selective and effective ligands for δ-opioid receptor.

  18. An experimental infection model for reproduction of calf pneumonia with bovine respiratory syncytial virus (BRSV) based on one combined exposure of calves

    DEFF Research Database (Denmark)

    Tjørnehøj, Kirsten; Uttenthal, Åse; Viuff, B.

    2003-01-01

    Bovine respiratory syncytial virus (BRSV) has been recognised as an important pathogen in calf pneumonia for 30 years, but surprisingly few effective infection models for studies of the immune response and the pathogenesis in the natural host have been established. We present a reproducible...

  19. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  20. Model Systems of Human Papillomavirus-Associated Disease

    OpenAIRE

    Doorbar, John

    2015-01-01

    Human Papillomaviruses (HPVs) cause a range of serious disease, including the vast majority of cervical cancers, most anal and vulval [AQ: comment from Reviewer, is this acceptable?] cancers and around half of head and neck cancers. They are also responsible for troublesome benign epithelial lesions, including genital warts and laryngeal papillomas, and in some individuals HPVs lead to recurrent respiratory papillomatosis and other difficult to manage diseases. As a result, there is a great n...

  1. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hara, Naomi; Morata, Saori

    2016-01-01

    -production was detected.Liver homogenate from the septic mice displayed a significant increase of the respiratory control ratio at 6 hours. In the 24-hour group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared to controls and the resultant respiratory...

  2. Respiratory effects of trichloroethylene.

    Science.gov (United States)

    Dumas, Orianne; Despreaux, Thomas; Perros, Frédéric; Lau, Edmund; Andujar, Pascal; Humbert, Marc; Montani, David; Descatha, Alexis

    2018-01-01

    Trichloroethylene (TCE) is a chlorinated solvent that has been used widely around the world in the twentieth century for metal degreasing and dry cleaning. Although TCE displays general toxicity and is classified as a human carcinogen, the association between TCE exposure and respiratory disorders are conflicting. In this review we aimed to systematically evaluate the current evidence for the respiratory effects of TCE exposure and the implications for the practicing clinician. There is limited evidence of an increased risk of lung cancer associated with TCE exposure based on animal and human data. However, the effect of other chlorinated solvents and mixed solvent exposure should be further investigated. Limited data are available to support an association between TCE exposure and respiratory tract disorders such as asthma, chronic bronchitis, or rhinitis. The most consistent data is the association of TCE with autoimmune and vascular diseases such as systemic sclerosis and pulmonary veno-occlusive disease. Although recent data are reassuring regarding the absence of an increased lung cancer risk with TCE exposure, clinicians should be aware of other potential respiratory effects of TCE. In particular, occupational exposure to TCE has been linked to less common conditions such as systemic sclerosis and pulmonary veno-occlusive disease. Copyright © 2017. Published by Elsevier Ltd.

  3. Implementing change in respiratory care.

    Science.gov (United States)

    Stoller, James K

    2010-06-01

    Though people are generally averse to change, change and innovation are critically important in respiratory care to maintain scientific and clinical progress. This paper reviews the issue of change in respiratory care. I summarize several available models of organizational and personal change (ie, those of Kotter and of Silversin and Kornacki, and the Intentional Change Theory of Boyatzis), review the characteristics of change-avid respiratory therapy departments, offer an example of a change effort in respiratory care (implementation of respiratory care protocols) and then analyze this change effort as it took place at one institution, the Cleveland Clinic, using these models. Finally, I present the results of an analysis of change-avid respiratory therapy departments and offer some suggestions regarding change management for the profession and for individual respiratory care clinicians. Common features of theories of organizational change include developing a sense of urgency, overcoming resistance, developing a guiding coalition, and involving key stakeholders early. With the understanding that change efforts may seem unduly "clean" and orderly in retrospect, the models help explain the sustainable success of efforts to implement the Respiratory Therapy Consult Service at the Cleveland Clinic. By implication, these models offer value in planning change efforts prospectively. Further analysis of features of change-avid respiratory therapy departments indicates 11 highly desired features, of which four that especially characterize change-avid departments include: having an up-to-date leadership team; employee involvement in change; celebrating wins; and an overall sense of progressiveness in the department. This analysis suggests that understanding and embracing change is important. To anchor change in our profession, greater attention should be given to developing a pipeline of respiratory care clinicians who, by virtue of their advanced training, have the skills

  4. Model Dinamik Penularan Human Immunodeficiency Virus (HIV)

    OpenAIRE

    Sutimin, Sutimin; Imamudin, Imamudin

    2009-01-01

    -Human Immunodeficiency Virus (HIV) adalah virus yang dapat merusak sistem kekebalan tubuh manusia Virus HIV dapat menyerang orang yang rentan ketika orang yang rentan itu melakukan kontak dengan penderita virus HIV hingga terinfeksi virus HIV pada akhirnya dapat menderita AIDS atau seropositif non-AIDS. Dengan asumsi-asumsi tentang penularan virus HIV dapat diformulasikan suatu model matematika tentang perpindahan antar orang-orang rentan ke infeksi HIV, penderita AIDS dan seropositif non-A...

  5. Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

    Directory of Open Access Journals (Sweden)

    Gustavo Rocha Garcia

    2012-10-01

    Full Text Available HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in São José do Rio Preto – SP, Brazi