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Pneumonia model

Marrit N Habets, Saskia van Selm, Fred J van Opzeeland, Elles Simonetti, Peter W M Hermans, Marien I de Jonge, Dimitri A Diavatopoulos
Widespread vaccination against Streptococcus pneumoniae (the pneumococcus) has significantly reduced pneumococcal disease caused by vaccine serotypes. Despite vaccination, overall pneumococcal colonization rates in children have not reduced and otitis media (OM) by non-vaccine serotypes remains one of the most common childhood infections. Pneumococcal surface protein A (PspA) has been shown to be a promising protein antigen to induce broad protection against pneumococcal colonization. However, its ability to protect against OM remains unclear...
October 19, 2016: Vaccine
Elena S Don, Alexandra G Emelyanova, Natalia N Yakovleva, Nataliia V Petrova, Marina V Nikiforova, Evgeniy A Gorbunov, Sergey A Tarasov, Sergey G Morozov, Oleg I Epstein
The assessment of dose-response is an essential part of drug development in terms of the determination of a drug's effective dose, finding the safety endpoint, estimation of the pharmacokinetic profile and even validation of drug activity, especially for therapeutic agents with a principally novel mechanism of action. Drugs based on released-active forms of antibodies are a good example of such a target. In this study, the efficacy of the antiviral drug Anaferon for children (released-active form of antibodies to interferon-gamma) was tested in a dose-dependent manner (at doses of 0...
October 21, 2016: Journal of Medical Virology
Jennifer H Madenspacher, Michael B Fessler
Although community-acquired pneumonia remains a major public health problem, murine models of bacterial pneumonia have recently facilitated significant preclinical advances in our understanding of the underlying cellular and molecular pathogenesis. In vivo mouse models capture the integrated physiology and resilience of the host defense response in a manner not revealed by alternative, simplified ex vivo approaches. Several methods have been described in the literature for intrapulmonary inoculation of bacteria in mice, including aerosolization, intranasal delivery, peroral endotracheal cannulation under 'blind' and visualized conditions, and transcutaneous endotracheal cannulation...
September 28, 2016: Journal of Visualized Experiments: JoVE
Wenfei Zhu, Hong Zhang, Xingyu Xiang, Lili Zhong, Lei Yang, Junfeng Guo, Yiran Xie, Fangcai Li, Zhihong Deng, Hong Feng, Yiwei Huang, Shixiong Hu, Xin Xu, Xiaohui Zou, Xiaodan Li, Tian Bai, Yongkun Chen, Zi Li, Junhua Li, Yuelong Shu
In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus...
November 2016: Emerging Infectious Diseases
Rupert M Pearse, Tom E Abbott, Richard Haslop, Tahania Ahmad, Brennan C Kahan, Claudia Filipini, Andrew Rhodes, Marco Ranieri
BACKGROUND: Over 300 million patients undergo surgery worldwide each year. Postoperative morbidity - particularly respiratory complications - are most frequent and severe among high-risk patients undergoing major abdominal surgery. However, standard treatments, like physiotherapy or supplemental oxygen, often fail to prevent these. Preliminary research suggests that prophylactic continuous positive airways pressure (CPAP) can reduce the risk of postoperative respiratory complications...
October 20, 2016: Minerva Anestesiologica
Erik Richter, Manuela Harms, Katharina Ventz, Rolf Nölker, Martin J Fraunholz, Jörg Mostertz, Falko Hochgräfe
Internalization of Staphylococcus aureus by non-professional phagocytic cells is a major suspected cause of persistent and difficult-to-treat infections, including pneumonia. In this study, we established an infection model with 16HBE14o- human bronchial epithelial cells and demonstrated internalization, escape from phagosomal clearance and intracellular replication of S. aureus HG001 within the first four hours post-infection. We used quantitative phosphoproteomics to identify characteristic signaling networks in the host at different infection stages...
October 20, 2016: Journal of Proteome Research
Y Liu, L Huang, H Ye, X Lv
Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and pneumonia. Here, a synthetic strategy that combined quantitative structure-activity relationship (QSAR)-based virtual screening and in vitro binding assay was described to identify new and potent mediator ligands of IRF-7 from natural products. In the procedure, a QSAR scoring function was developed and validated using Gaussian process (GP) regression and a structure-based set of protein-ligand affinity data. By integrating hotspot pocket prediction, pharmacokinetics profile analysis and molecular docking calculations, the scoring function was successfully applied to virtual screening against a large library of structurally diverse, drug-like natural products...
October 20, 2016: SAR and QSAR in Environmental Research
James C Hurley
BACKGROUND: Acinetobacter species such as Acinetobacter baumanii are of increasing concern in association with ventilator associated pneumonia (VAP). In the ICU, Acinetobacter infections are known to be subject to seasonal variation but the extent of geographic variation is unclear. The objective here is to define the extent and possible reasons for geographic variation for Acinetobacter associated VAP whether or not these isolates are reported as Acinetobacter baumanii. METHODS: A meta-regression model of VAP associated Acinetobacter incidence within the published literature was undertaken using random effects methods...
October 18, 2016: BMC Infectious Diseases
Alessandro Cassini, Diamantis Plachouras, Tim Eckmanns, Muna Abu Sin, Hans-Peter Blank, Tanja Ducomble, Sebastian Haller, Thomas Harder, Anja Klingeberg, Madlen Sixtensson, Edward Velasco, Bettina Weiß, Piotr Kramarz, Dominique L Monnet, Mirjam E Kretzschmar, Carl Suetens
BACKGROUND: Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011-2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs...
October 2016: PLoS Medicine
Robert E Burke, Jeffrey L Schnipper, Mark V Williams, Edmondo J Robinson, Eduard E Vasilevskis, Sunil Kripalani, Joshua P Metlay, Grant S Fletcher, Andrew D Auerbach, Jacques D Donzé
BACKGROUND/OBJECTIVES: New tools to accurately identify potentially preventable 30-day readmissions are needed. The HOSPITAL score has been internationally validated for medical inpatients, but its performance in select conditions targeted by the Hospital Readmission Reduction Program (HRRP) is unknown. DESIGN: Retrospective cohort study. SETTING: Six geographically diverse medical centers. PARTICIPANTS/EXPOSURES: All consecutive adult medical patients discharged alive in 2011 with 1 of the 4 medical conditions targeted by the HRRP (acute myocardial infarction, chronic obstructive pulmonary disease, pneumonia, and heart failure) were included...
October 14, 2016: Medical Care
Xiuting Mo, Ruoyan Gai Tobe, Xiaoyan Liu, Rintaro Mori
BACKGROUND: Each year in China, approximately 700,000 children under 5 years old are diagnosed with pneumonia, and 30,000 die of the disease. Although 7-valent pneumococcal conjugate vaccine (PCV-7) and 23-valent pneumococcal polysaccharide vaccine (PPV-23) are available in China, the costs are borne by the consumer, resulting in low coverage for PCV-7. We aimed to conduct a simulation study to assess the cost-effectiveness and health benefits of PCV-7, 13-valent pneumococcal conjugate vaccine (PCV-13) and PPV-23 to prevent childhood pneumonia and other vaccine-preventive diseases in China...
November 2016: Pediatric Infectious Disease Journal
Anuj B Mehta, Colin R Cooke, Ivor S Douglas, Peter K Lindenauer, Renda Soylemez Wiener, Allan J Walkey
RATIONALE: In the United States, approximately 20% of patients hospitalized with pneumonia are readmitted to a hospital within 30 days. Given the significant costs and healthcare system utilization due to unplanned readmissions, pneumonia readmission rates are a target of national quality measures. Patient do-not-resuscitate (DNR) status strongly influences hospital pneumonia mortality measures; however, associations between DNR status and 30-day readmissions following pneumonia are unclear...
October 18, 2016: Annals of the American Thoracic Society
Francis Mawanda, Robert B Wallace, Kimberly McCoy, Thad E Abrams
INTRODUCTION: Emerging evidence indicates associations between extra-central nervous system (CNS) bacterial infections and an increased risk for dementia; however, epidemiological evidence is still very limited. METHODS: This study involved a retrospective cohort of a national sample of US veterans (N = 417,172) aged ≥56 years. Extended Cox proportional hazard models adjusted for demographic characteristics and medical and psychiatric comorbidities determined the associations between systemic and localized extra-CNS bacterial infections occurring >2 years before the initial dementia diagnosis and the risk for dementia...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Rachel Boxio, Julien Wartelle, Béatrice Nawrocki-Raby, Brice Lagrange, Laurette Malleret, Timothee Hirche, Clifford Taggart, Yves Pacheco, Gilles Devouassoux, Abderrazzaq Bentaher
BACKGROUND: In acutely injured lungs, massively recruited polymorphonuclear neutrophils (PMNs) secrete abnormally neutrophil elastase (NE). Active NE creates a localized proteolytic environment where various host molecules are degraded leading to impairment of tissue homeostasis. Among the hallmarks of neutrophil-rich pathologies is a disrupted epithelium characterized by the loss of cell-cell adhesion and integrity. Epithelial-cadherin (E-cad) represents one of the most important intercellular junction proteins...
October 17, 2016: Respiratory Research
Olivier Huet, Raelene J Pickering, Chris Tikellis, Celine Latouche, Fenella Long, Bronwyn Kingwell, Bryan Dickinson, Chris J Chang, Seth Masters, Fabienne Mackay, Mark E Cooper, Judy B de Haan
OBJECTIVES: To study the effect of a lack of antioxidant defenses during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice. SETTING: Laboratory experiments. SUBJECTS: C57Bl6 and glutathione peroxidase 1 knockout mice. INTERVENTION: Murine acute pneumonia model induced by Klebsiella pneumonia. MEASUREMENTS AND MAIN RESULTS: We show here that despite a lack of one of the major antioxidant defense enzymes, glutathione peroxidase 1 knockout mice are protected during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice...
October 3, 2016: Critical Care Medicine
Thomas S Valley, Allan J Walkey, Peter K Lindenauer, Renda Soylemez Wiener, Colin R Cooke
OBJECTIVE: Despite increasing use, evidence is mixed as to the appropriate use of noninvasive ventilation in patients with pneumonia. We aimed to determine the relationship between receipt of noninvasive ventilation and outcomes for patients with pneumonia in a real-world setting. DESIGN, SETTING, PATIENTS: We performed a retrospective cohort study of Medicare beneficiaries (aged > 64 yr) admitted to 2,757 acute-care hospitals in the United States with pneumonia, who received mechanical ventilation from 2010 to 2011...
October 5, 2016: Critical Care Medicine
Zhuo Wu, Qinxia Xu, Xiaoyan Qiu, Zheng Jiao, Ming Zhang, Mingkang Zhong
PURPOSE: The purpose of this study was to investigate the potential impact of FOXP3 and CCDC22 gene polymorphisms on efficacy and safety of tacrolimus (TAC) in renal transplant patients. METHODS: Genetic polymorphisms were detected in 114 Chinese renal transplant patients who were on TAC-based maintenance immunosuppression and were followed up for at least 2 years. The relationships between FOXP3 rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22 rs2294021 polymorphisms and clinical outcomes such as acute rejection, TAC-induced acute nephrotoxicity, and pneumonia were investigated by using Kaplan-Meier estimates and multivariate Cox regression analysis...
October 17, 2016: European Journal of Clinical Pharmacology
Alexandra E Paharik, Wilmara Salgado-Pabon, David K Meyerholz, Mark J White, Patrick M Schlievert, Alexander R Horswill
The Spl proteases are a group of six serine proteases that are encoded on the νSaβ pathogenicity island and are unique to Staphylococcus aureus. Despite their interesting biochemistry, their biological substrates and functions in virulence have been difficult to elucidate. We found that an spl operon mutant of the community-associated methicillin-resistant S. aureus USA300 strain LAC induced localized lung damage in a rabbit model of pneumonia, characterized by bronchopneumonia observed histologically. Disease in the mutant-infected rabbits was restricted in distribution compared to that in wild-type USA300-infected rabbits...
September 2016: MSphere
Ita Muharram Sari, Lyna Soertidewi, Chiaki Yokota, Muneaki Kikuno, Masatoshi Koga, Kazunori Toyoda
BACKGROUND: Pneumonia is one of the most common medical complications after stroke. Incidence and risk factor analyses of stroke-associated pneumonia (SAP) in stroke care units (SCUs) are limited. SAP incidence comparisons across countries can identify the most effective treatment to reduce this incidence. METHODS: This was a retrospective study including consecutive patients with acute stroke in SCUs in 2 hospitals: 105 patients (mean age 78.2 ± 5.8) from the National Cerebral and Cardiovascular Center (NCVC) in Osaka, Japan (from July to August 2015), and 105 patients (mean age 60 ± 5...
October 13, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Paul M Arnaboldi, Mariya Sambir, Christina D'Arco, Lauren A Peters, Jos F M L Seegers, Lloyd Mayer, Alison A McCormick, Raymond J Dattwyler
Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y...
October 13, 2016: Vaccine
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