scholarly journals Use of Thoracic Ultrasonography to Improve Disease Detection in Experimental BRD Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Madison M. Porter ◽  
Paiton O. McDonald ◽  
Jamison R. Slate ◽  
Amanda J. Kreuder ◽  
Jodi L. McGill
Keyword(s):  
Immune Status ◽  
Vital Signs ◽  
Nasal Discharge ◽  
Clinical Settings ◽  
Lung Pathology ◽  
Calf Health ◽  
Additional Information ◽  
Complex Interactions ◽  
Clinical Scoring ◽  
Syncytial Virus

Bovine respiratory disease (BRD) is caused by complex interactions between viral and bacterial pathogens, host immune status, and environmental stressors. In both clinical and research settings, current methods for detecting BRD in calves commonly focus on visual indicators such as attitude, nasal discharge, and cough, in addition to vital signs such as rectal temperature and respiration rate. Recently, thoracic ultrasonography (TUS) has become more commonly used in clinical settings, in addition to physical examination to diagnose BRD. To assess the value of performing TUS during experimental BRD infection, 32 calves were challenged with bovine respiratory syncytial virus, to mimic a viral infection, and 30 calves were infected with Mannheimia haemolytica, to mimic a bacterial infection. TUS was performed at regular intervals using a standardized method and scoring system in addition to daily clinical scoring. Although overall correlations between clinical scores and TUS scores were generally weak (maximum R2 = 0.3212), TUS identified calves with abnormal lung pathology that would have otherwise been misclassified on the basis of clinical scoring alone, both on arrival and throughout the studies. In addition, TUS had an increased correlation with gross lung pathology on necropsy (maximum R2 = 0.5903), as compared to clinical scoring (maximum R2 = 0.3352). Our results suggest that TUS can provide additional information on calf health at enrollment and throughout a study and may provide an alternative to terminal studies, due to the high correlation with lung pathology at necropsy.

scholarly journals Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus.

1988 ◽  
Vol 168 (3) ◽  
pp. 1163-1168 ◽  
Author(s):  
M J Cannon ◽  
P J Openshaw ◽  
B A Askonas
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cell Line ◽  
Respiratory Disease ◽  
Cytotoxic T Cells ◽  
Lung Pathology ◽  
Class I Mhc ◽  
Rsv Infection ◽  
Syncytial Virus

We have examined the function of class I MHC-restricted cytotoxic T cells in experimental respiratory syncytial virus (RSV) infection of BALB/c mice by transfer of T cell line MJC-A2 and CTL clone E8a into RSV-infected mice. The T cell line cleared pulmonary RSV infection within 5 d in persistently infected gamma-irradiated mice, but caused acute respiratory disease. This was only seen in infected mice and was often lethal after transfer of greater than 3 x 10(6) CTL. Lower numbers of CTL produced less severe disease but still cleared lung RSV, albeit over a longer time course (up to 10 d). Clearance of lung RSV in immunocompetent mice by the T cell line and CTL clone was again accompanied by acute and sometimes lethal respiratory disease. Bronchoalveolar lavage showed severe lung hemorrhage and frequent neutrophil efflux in mice with CTL-augmented disease.

scholarly journals Development and validation of a prognostic model for early triage of patients diagnosed with COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chansik An ◽  
Hyun Cheol Oh ◽  
Jung Hyun Chang ◽  
Seung-Jin Oh ◽  
Jung Mo Lee ◽  
...  
Keyword(s):  
Prognostic Score ◽  
External Validation ◽  
Vital Signs ◽  
Underlying Disease ◽  
Test Results ◽  
Additional Information ◽  
Patient Will ◽  
National Cohort ◽  
Evaluation Metric ◽  
Development And Validation

AbstractWe developed a tool to guide decision-making for early triage of COVID-19 patients based on a predicted prognosis, using a Korean national cohort of 5,596 patients, and validated the developed tool with an external cohort of 445 patients treated in a single institution. Predictors chosen for our model were older age, male sex, subjective fever, dyspnea, altered consciousness, temperature ≥ 37.5 °C, heart rate ≥ 100 bpm, systolic blood pressure ≥ 160 mmHg, diabetes mellitus, heart disease, chronic kidney disease, cancer, dementia, anemia, leukocytosis, lymphocytopenia, and thrombocytopenia. In the external validation, when age, sex, symptoms, and underlying disease were used as predictors, the AUC used as an evaluation metric for our model’s performance was 0.850 in predicting whether a patient will require at least oxygen therapy and 0.833 in predicting whether a patient will need critical care or die from COVID-19. The AUCs improved to 0.871 and 0.864, respectively, when additional information on vital signs and blood test results were also used. In contrast, the protocols currently recommended in Korea showed AUCs less than 0.75. An application for calculating the prognostic score in COVID-19 patients based on the results of this study is presented on our website (https://nhimc.shinyapps.io/ih-psc/), where the results of the validation ongoing in our institution are periodically updated.

A Survey of Parental Knowledge of Respiratory Syncytial Virus and Other Respiratory Infections in Preterm Infants

2021 ◽  
Vol 40 (1) ◽  
pp. 14-24
Author(s):  
Marianne Bracht ◽  
Fabiana Bacchini ◽  
Bosco Paes
Keyword(s):  
Respiratory Syncytial Virus ◽  
Preterm Infants ◽  
Disease Risk ◽  
Respiratory Infections ◽  
Parental Knowledge ◽  
Good Knowledge ◽  
Sources Of Information ◽  
Eligibility Criteria ◽  
Additional Information ◽  
Syncytial Virus

PurposeEvaluate parental knowledge of respiratory syncytial virus (RSV) and other respiratory infections in preterm infants.DesignSurvey.SampleFive hundred and eighty-three parents of preterm infants with generalized, Canadian provincial representation.Main OutcomeKnowledge of RSV infection, sources of information, and parental understanding of disease risk.Results97.9 percent (571/583) of the parents had heard about RSV, since they all had a preterm infant. Sixty-one percent reported having good knowledge of RSV; 19.4 percent had very good knowledge; 19.7 percent had little or no awareness of RSV-related infection. Most (86.3 percent) believed that RSV illness was a very serious condition; 13 percent recognized that it could be a major problem for their child. Principal sources of information were the nurse, doctor and pamphlets. Over 480 participants cited 3 or more sources of additional information—Internet, social media platforms, and educational sessions. Respiratory syncytial virus prophylaxis was a priority, but knowledge regarding the eligibility criteria for prophylaxis is essential.

scholarly journals Supplementing a Saccharomyces cerevisiae fermentation product modulates innate immune function and ameliorates bovine respiratory syncytial virus infection in neonatal calves

2020 ◽  
Vol 98 (8) ◽  
Author(s):  
Asmaa H A Mahmoud ◽  
Jamison R Slate ◽  
Suyeon Hong ◽  
Ilkyu Yoon ◽  
Jodi L McGill
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Respiratory Syncytial Virus ◽  
Immune Function ◽  
Clinical Signs ◽  
Bovine Respiratory Syncytial Virus ◽  
Dairy Calves ◽  
Lung Pathology ◽  
Fermentation Products ◽  
Supplementation Period ◽  
Syncytial Virus

Abstract The objectives of this study were to determine the effects of oral supplementation with Saccharomyces cerevisiae fermentation products (SCFP; SmartCare and NutriTek; Diamond V, Cedar Rapids, IA) on immune function and bovine respiratory syncytial virus (BRSV) infection in preweaned dairy calves. Twenty-four Holstein × Angus, 1- to 2-d-old calves (38.46 ± 0.91 kg initial body weight [BW]) were assigned two treatment groups: control or SCFP treated, milk replacer with 1 g/d SCFP (SmartCare) and calf starter top-dressed with 5 g/d SCFP (NutriTek). The study consisted of one 31-d period. On days 19 to 21 of the supplementation period, calves were challenged via aerosol inoculation with BRSV strain 375. Calves were monitored twice daily for clinical signs, including rectal temperature, cough, nasal and ocular discharge, respiration effort, and lung auscultation. Calves were euthanized on day 10 postinfection (days 29 to 31 of the supplementation period) to evaluate gross lung pathology and pathogen load. Supplementation with SCFP did not affect BW (P = 0.762) or average daily gain (P = 0.750), percentages of circulating white blood cells (P < 0.05), phagocytic (P = 0.427 for neutrophils and P = 0.460 for monocytes) or respiratory burst (P = 0.119 for neutrophils and P = 0.414 for monocytes) activity by circulating leukocytes either before or following BRSV infection, or serum cortisol concentrations (P = 0.321) after BRSV infection. Calves receiving SCFP had reduced clinical disease scores compared with control calves (P = 0.030), reduced airway neutrophil recruitment (P < 0.002), reduced lung pathology (P = 0.031), and a reduced incidence of secondary bacterial infection. Calves receiving SCFP shed reduced virus compared with control calves (P = 0.049) and tended toward lower viral loads in the lungs (P = 0.051). Immune cells from the peripheral blood of SCFP-treated calves produced increased (P < 0.05) quantities of interleukin (IL)-6 and tumor necrosis factor-alpha in response to toll-like receptor stimulation, while cells from the bronchoalveolar lavage (BAL) of SCFP-treated calves secreted less (P < 0.05) proinflammatory cytokines in response to the same stimuli. Treatment with SCFP had no effect on virus-specific T cell responses in the blood but resulted in reduced (P = 0.045) virus-specific IL-17 secretion by T cells in the BAL. Supplementing with SCFP modulates both systemic and mucosal immune responses and may improve the outcome of an acute respiratory viral infection in preweaned dairy calves.

scholarly journals Antiviral Efficacy of a Respiratory Syncytial Virus (RSV) Fusion Inhibitor in a Bovine Model of RSV Infection

2015 ◽  
Vol 59 (8) ◽  
pp. 4889-4900 ◽  
Author(s):  
Robert Jordan ◽  
Matt Shao ◽  
Richard L. Mackman ◽  
Michel Perron ◽  
Tomas Cihlar ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Structural Analog ◽  
Therapeutic Benefit ◽  
Viral Envelope ◽  
Fusion Inhibitor ◽  
Lung Pathology ◽  
Host Cell Membrane ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV.

scholarly journals Host Transcription Profiles upon Primary Respiratory Syncytial Virus Infection

2007 ◽  
Vol 81 (11) ◽  
pp. 5958-5967 ◽  
Author(s):  
Riny Janssen ◽  
Jeroen Pennings ◽  
Hennie Hodemaekers ◽  
Annemarie Buisman ◽  
Marijke van Oosten ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Lymph Nodes ◽  
Viral Replication ◽  
Transcriptional Level ◽  
Type I ◽  
Lung Pathology ◽  
Transcription Profiles ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in children. Severe RSV disease is related to an inappropriate immune response to RSV resulting in enhanced lung pathology which is influenced by host genetic factors. To gain insight into the early pathways of the pathogenesis of and immune response to RSV infection, we determined the transcription profiles of lungs and lymph nodes on days 1 and 3 after infection of mice. Primary RSV infection resulted in a rapid but transient innate, proinflammatory response, as exemplified by the induction of a large number of type I interferon-regulated genes and chemokine genes, genes involved in inflammation, and genes involved in antigen processing. Interestingly, this response is much stronger on day 1 than on day 3 after infection, indicating that the strong transcriptional response in the lung precedes the peak of viral replication. Surprisingly, the set of down-regulated genes was small and none of these genes displayed strong down-regulation. Responses in the lung-draining lymph nodes were much less prominent than lung responses and are suggestive of NK cell activation. Our data indicate that at time points prior to the peak of viral replication and influx of inflammatory cells, the local lung response, measured at the transcriptional level, has already dampened down. The processes and pathways induced shortly after RSV infection can now be used for the selection of candidate genes for human genetic studies of children with severe RSV infection.

scholarly journals Towards standardization of immune functional assays

2019 ◽  
Author(s):  
William Mouton ◽  
Chloé Albert Vega ◽  
Mathilde Boccard ◽  
François Bartolo ◽  
Guy Oriol ◽  
...  
Keyword(s):  
Immune Function ◽  
Host Response ◽  
Immune Status ◽  
Immune Dysfunction ◽  
Function Evaluation ◽  
Clinical Settings ◽  
Adaptive Immune ◽  
Independent Validation ◽  
Functional Assays ◽  
Therapeutic Decisions

AbstractRecent advances in the immunotherapy field require evaluation of the immune function to adapt therapeutic decisions. Immune functional assays (IFA) are able to reveal the immune status and would be useful to further adapt/improve patient’s care. However, standardized methods are needed to implement IFA in clinical settings. We carried out an independent validation of a published method used to characterize the underlying host response to infectious conditions using an IFA. We evaluate the reproducibility and robustness of this IFA and associated readout using an independent healthy volunteers (HV) cohort. Expression of a 44 genes-signatures and IFNγ protein secretion and gene-expression was assessed after stimulation. We observed a strong host-response correlation between the two cohorts. We also highlight that standardized methods for immune function evaluation exist and could be implemented in larger-scale studies. This IFA could be a relevant tool to reveal innate/adaptive immune dysfunction in immune-related disorders patients.

scholarly journals Prototipo para la comparación de patrones temporales secuenciales de arritmias cardíacas [Prototype for comparison of sequential temporal patterns of cardiac arrhythmias]

2012 ◽  
Author(s):  
Alejandro Javier Hadad ◽  
Agustín Benjamín Ezequiel Solano ◽  
Bartolomé Drozdowicz
Keyword(s):  
Critical Care ◽  
Cardiac Arrhythmias ◽  
Temporal Patterns ◽  
Clinical Settings ◽  
Analysis Model ◽  
Reference Case ◽  
Software Application ◽  
Critical Care Units ◽  
Additional Information

Resumen En el presente trabajo se presenta un prototipo para la búsqueda de patrones temporales secuenciales de arritmias cardíacas. Dicha búsqueda está orientada al soporte de tareas de monitoreo en ámbitos clínicos a través de modelos de seguimiento temporal en unidades de cuidados críticos. En el proceso de diseño se abordaron diferentes dimensiones de análisis desde el punto de vista de la abstracción temporal. Para el desarrollo de los modelos de seguimiento se eligió como caso de referencia el monitoreo de las arritmias. Para el análisis de secuencias se construyó un modelo basado en el algoritmo de Smith-Waterman. El seguimiento con este modelo generó información adicional, potencialmente utilizable en el pronóstico de evolución en cuidados críticos. Con estas especificaciones se desarrolló una aplicación de software que tiene como objetivo principal comparar y ponderar registros de electrocardiograma (ECG), clasificados según diferentes tipos de latidos. La aplicación funciona como soporte para la exploración y el análisis con fines diagnósticos de afecciones evidenciadas a partir de arritmias cardíacas, brindando indicios acerca de la evolución temporal entre registros similares. Palabras ClavesPrototipo, Supervisión, Arritmias, Patrones temporales   Abstract This paper presents a prototype for the sequential search for temporal patterns of cardiac arrhythmias. This search is aimed at supporting monitoring tasks in clinical settings through time tracking models in critical care units. In the design process are addressed different dimensions of analysis from the viewpoint of abstraction in time. For the development of monitoring models was taken as the reference case monitoring of arrhythmias. The sequence analysis model was constructed based on the Smith-Waterman algorithm. Follow-up with this model generated information, potentially useful in forecasting trends in critical care. With these specifications the software application was developed to compare and weight electrocardiogram records. The application work like a support to exploration and analysis diagnostic tasks over illness related to cardiac arrhythmias and generate additional information about the evolution based on historical with similar sequential temporal patterns. Keywords Prototype, Supervision, Arrhythmias, Temporal patterns 

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