Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.     

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.     

Fire exclusion and the changing landscape of Queensland’s Wet Tropics Bioregion 1. The extent and pattern of transition

The vegetation and geology of the Wet Tropics Bioregion of North Queensland, covering 1?998?150 ha, were mapped at a scale of 1:50?000. The resulting geographic information system (GIS) data base provided an unprecedented opportunity to examine vegetation condition across the entire bioregion. Mapping used colour aerial photography at 1:25?000, informed by ground truthing. Vegetation type, nature of the understory and ground cover, degree and type of disturbance, and the presence of secondary vegetation were described by a coding system, with codes marked directly on the aerial photos.

Analysis of these data has confirmed a picture, which emerged from ground truthing, of large areas of sclerophyll woodland and forest being invaded by a rainforest understory that prevents regeneration of the sclerophyll canopy. Fifty-three per cent of the native vegetation of the bioregion consists of non-rainforest vegetation types, dominated in both area and number by sclerophyll woodlands and forests. Seventeen per cent of the 735?713 ha of sclerophyll woodland and forest types were assessed as having suffered irreversible change. Between 25% and 79% of individual forest vegetation types were judged to have been affected by irreversible change. No climatic changes, or changes in the environment, apart from those related to changing fire regimes, were identified as causative factors. Changed fire regimes, predominantly fire exclusion, are considered to be the most likely cause.     

Propionibacterium acnes: infection beyond the skin

Propionibacterium acnes is a Gram-positive bacterium that forms part of the normal flora of the skin, oral cavity, large intestine, the conjunctiva and the external ear canal. Although primarily recognized for its role in acne, P. acnes is an opportunistic pathogen, causing a range of postoperative and device-related infections. These include infections of the bones and joints, mouth, eye and brain. Device-related infections include those of joint prostheses, shunts and prosthetic heart valves. P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer, SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, sarcoidosis and sciatica. If an active role in these conditions is established there are major implications for diagnosis, treatment and protection. Genome sequencing of the organism has provided an insight into the pathogenic potential and virulence of P. acnes.     

论张仲景“客气”之意

张仲景书中的"客气"一词,一般被误解作"邪气"。笔者通过比较多条经文发现,"客气"并非张仲景理解的"邪气",而是指一种特殊的致病因素,是由于胃虚而浊气上逆所生的阳热之邪。由于这种情况并非"外来邪气",又非生理的"正气",因而张仲景创造"客气"一词,以解释这种特殊的病因。     

Advances in multiplex nucleic acid diagnostics for blood-borne pathogens: promises and pitfalls - an update

Introduction: Multiplex nucleic acid diagnostics for blood-borne pathogens have moved closer to clinical application in the two years since we first reviewed this topic.

Areas covered: A new emphasis on detecting pathogens directly in a blood sample without culture, coupling PCR amplification to microfluidic devices and higher multiplexing in isothermal amplification are some of the advances. A wholly new approach of correlating host gene expression response with specific infectious agents opens another opportunity for multiplex detection. Established microarrays, which had been the highest multiplicity platform, are being displaced by Next Generation Sequencing (NGS) having potentially no limit to the number of pathogens that it can identify. Greater accessibility of sequencing devices, standardization of bioinformatic analysis pathways and increased acceptance from regulatory authorities are driving this technology.

Expert commentary: The landscape of traditional diagnostics for detection of blood-borne pathogens has changed in the last 5 years. There is no doubt that NSG is recognized as a disruptive technology with a growing repertoire of tools, such as subtyping, resistome analysis, etc., available for clinical microbiology. Increasing acceptance indicates the dominating position of NGS as the future of multiplex molecular diagnostics for blood-borne pathogens.     

Augmented Reality Farm MAPPER Development: Lessons Learned from an App Designed to Improve Rural Emergency Response

Fire departments have right-of-entry to most commercial industrial sites and preemptively map them to identify the onsite resources and hazards they need to promptly and safely respond to an emergency event. This is not the case for private farms. Emergency responders are blind to resources and hazards prior to arrival and must spend critical minutes locating them during an emergency response at a farm location. The original 2013 Farm Mapping to Assist, Protect and Prepare Emergency Responders (Farm MAPPER) project was undertaken to develop a method to give emergency responders an up-to-date view of on-farm hazard information to safely and efficiently conduct emergency response activities on private agricultural operations. In 2017, an augmented reality version of Farm MAPPER was developed to combine the technological advantages of geographic information system-based data points with a heads-up display and graphical overlay of superimposed hazard imagery and informative icons. The development and testing of this iOS- and Android-ready prototype uncovered lessons learned applicable to other mobile-based apps targeting farmers, ranchers, and rural populations faced with limited or inconsistent mobile internet connectivity.     

Where is Chlamydophila pneumoniae pneumonia?

BackgroundMolecular diagnostic methods have recently gained widespread use, and consequently, the importance of viral pathogens in community-acquired pneumonia (CAP) has undergone re-evaluation. Under these circumstances, the role of Chlamydophila pneumoniae as a pathogen that causes CAP also needs to be reviewed.MethodsWe reviewed articles that contained data on the frequency of identification of C. pneumoniae pneumonia as a causative pathogen for CAP. The articles were identified by performing a search in PubMed with the keywords “community-acquired pneumonia” and “pathogen”.ResultsSixty-three articles were identified. The reviewed articles demonstrated that the rates of identification of C. pneumoniae as the causative pathogen for CAP were significantly lower in assessments based on polymerase chain reaction (PCR) methods than in those based on serological methods. In some studies, it was possible to compare both serological and PCR methods directly using the same set of samples.ConclusionsThe use of PCR methods, including multiplex PCR assays, has revealed that C. pneumoniae may play a limited role as a pathogen for CAP.     

Synovial fluid multiplex PCR is superior to culture for detection of low-virulent pathogens causing periprosthetic joint infection

Introduction

Analysis of joint aspirate is the standard preoperative investigation for diagnosis of periprosthetic joint infection (PJI). We compared the diagnostic performance of culture and multiplex polymerase chain reaction (PCR) of synovial fluid for diagnosis of PJI.