title: Emergence and adaptive evolution of Nipah virus

text: Since its first emergence in 1998 in Malaysia, Nipah virus (NiV) has become a great threat to domestic animals and humans. Sporadic outbreaks associated with human‐to‐human transmission caused hundreds of human fatalities. Here, we collected all available NiV sequences and combined phylogenetics, molecular selection, structural biology and receptor analysis to study the emergence and adaptive evolution of NiV. NiV can be divided into two main lineages including the Bangladesh and Malaysia lineages. We formly confirmed a significant association with geography which is probably the result of long‐term evolution of NiV in local bat population. The two NiV lineages differ in many amino acids; one change in the fusion protein might be involved in its activation via binding to the G protein. We also identified adaptive and positively selected sites in many viral proteins. In the receptor‐binding G protein, we found that sites 384, 386 and especially 498 of G protein might modulate receptor‐binding affinity and thus contribute to the host jump from bats to humans via the adaption to bind the human ephrin‐B2 receptor. We also found that site 1645 in the connector domain of L was positive selected and involved in adaptive evolution; this site might add methyl groups to the cap structure present at the 5′‐end of the RNA and thus modulate its activity. This study provides insight to assist the design of early detection methods for NiV to assess its epidemic potential in humans.


Whether the GFR measured by renal scintigraphy under non-steady state conditions for critically ill patients with AKI can be used as a predictive parameter for clinical events


title: Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study

text: BACKGROUND: Approximately 30% of children worldwide are infected with gastrointestinal parasites. Depending on the species, parasites can disrupt intestinal bacterial microbiota affecting essential vitamin biosynthesis. METHODS: Stool samples were collected from 37 asymptomatic children from a previous cross-sectional Argentinian study. A multi-parallel real-time quantitative PCR was implemented for Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica and Giardia duodenalis. In addition, whole-genome sequencing analysis was conducted for bacterial microbiota on all samples and analyzed using Livermore Metagenomic Analysis Toolkit and DIAMOND software. Separate analyses were carried out for uninfected, Giardia-only, Giardia + helminth co-infections, and helminth-only groups. RESULTS: For Giardia-only infected children compared to uninfected children, DNA sequencing data showed a decrease in microbiota biodiversity that correlated with increasing Giardia burden and was statistically significant using Shannonʼs alpha diversity (Giardia-only > 1 fg/µl 2.346; non-infected group 3.253, P = 0.0317). An increase in diversity was observed for helminth-only infections with a decrease in diversity for Giardia + helminth co-infections (P = 0.00178). In Giardia-only infections, microbiome taxonomy changed from Firmicutes towards increasing proportions of Prevotella, with the degree of change related to the intensity of infection compared to uninfected (P = 0.0317). The abundance of Prevotella bacteria was decreased in the helminths-only group but increased for Giardia + helminth co-infections (P = 0.0262). Metagenomic analysis determined cobalamin synthesis was decreased in the Giardia > 1 fg/µl group compared to both the Giardia < 1 fg/µl and the uninfected group (P = 0.0369). Giardia + helminth group also had a decrease in cobalamin CbiM genes from helminth-only infections (P = 0.000754). CONCLUSION: The study results may provide evidence for an effect of parasitic infections enabling the permissive growth of anaerobic bacteria such as Prevotella, suggesting an altered capacity of vitamin B12 (cobalamin) biosynthesis and potential impact on growth and development in children [Image: see text].


title: Initially elevated arterial lactate as an independent predictor of poor outcomes in severe acute pancreatitis

text: BACKGROUND: The present study aimed to investigate the relationships between arterial lactate levels and outcomes in severe acute pancreatitis. METHODS: The study retrospectively analyzed the medical data of 329 patients with severe acute pancreatitis from January 2014 to February 2019. We compared baseline characteristics, laboratory data, severity scores, types of persistent organ failure, and primary and secondary outcomes of patients with and without elevated arterial lactate levels at admission. A multivariate logistic regression analysis model and receiver operating characteristic curve were adopted to evaluate the value of arterial lactate ≥4 mmol/L for identifying high-risk patients. Trends in arterial lactate levels were compared between patients in the survivor and nonsurvivor groups over a period of 7 days. RESULTS: Compared to normal arterial lactate levels, patients with elevated arterial lactate levels show significantly higher incidences of multiple persistent organ failure (3% vs 30%, P < 0.01), death (2% vs 11%, P < 0.01), septic shock (4% vs 24%, P < 0.01), pancreatic infection (12% vs 37%, P < 0.01), abdominal compartment syndrome (3% vs 20%, P < 0.01), pancreatic necrosis (41% vs 63%, P < 0.01), and a need for ventilator support (26% vs 54%, P < 0.01). For predicting mortality, arterial lactate levels ≥4 mmol/L had a high hazard ratio (10, 95% CI; 3.7–27; P < 0.01) and the highest area under the curve (0.78). CONCLUSIONS: Our results indicate that initially elevated arterial lactate is independently associated with poor outcomes and death in patients with severe acute pancreatitis and may serve as an early high-risk stratification indicator.


From the Editors


title: The ubiquitin‐proteasome system in positive‐strand RNA virus infection

text: Positive‐stranded RNA viruses, like many other viruses, have evolved to exploit the host cellular machinery to their own advantage. In eukaryotic cells, the ubiquitin‐proteasome system (UPS) that serves as the major intracellular pathway for protein degradation and modification plays a crucial role in the regulation of many fundamental cellular functions. A growing amount of evidence has suggested that the UPS can be utilized by positive‐sense RNA viruses. The UPS eliminates excess viral proteins that prevent viral replication and modulates the function of viral proteins through post‐translational modification mediated by ubiquitin or ubiquitin‐like proteins. This review will discuss the current understanding of how positive RNA viruses have evolved various mechanisms to usurp the host UPS to modulate the function and stability of viral proteins. In addition to the pro‐viral function, UPS‐mediated viral protein degradation may also constitute a host defense process against some positive‐stranded RNA viral infections. This issue will also be discussed in the current review. Copyright © 2012 John Wiley & Sons, Ltd.


Abstracts for the Annual Scientific Meeting of the Thoracic Society of Australia & New Zealand ‘Maintaining Lung Health from Cradle to Grave’ 7–12 April 2000, Melbourne, Australia


title: Reasoned Decision Making Without Math? Adaptability and Robustness in Response to Surprise

text: Many real‐world planning and decision problems are far too uncertain, too variable, and too complicated to support realistic mathematical models. Nonetheless, we explain the usefulness, in these situations, of qualitative insights from mathematical decision theory. We demonstrate the integration of info‐gap robustness in decision problems in which surprise and ignorance are predominant and where personal and collective psychological factors are critical. We present practical guidelines for employing adaptable‐choice strategies as a proxy for robustness against uncertainty. These guidelines include being prepared for more surprises than we intuitively expect, retaining sufficiently many options to avoid premature closure and conflicts among preferences, and prioritizing outcomes that are steerable, whose consequences are observable, and that do not entail sunk costs, resource depletion, or high transition costs. We illustrate these concepts and guidelines with the example of the medical management of the 2003 SARS outbreak in Vietnam.


title: Clinical relevance of necrotizing change in patients with community‐acquired pneumonia

text: BACKGROUND AND OBJECTIVE: Few studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community‐acquired pneumonia (CAP). METHODS: This retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non‐NP groups, and they were compared with respect to various clinical variables. RESULTS: Of the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non‐NP. Although the use of mechanical ventilation, vasopressor infusion, 30‐day mortality, in‐hospital mortality and clinical deterioration did not differ between the NP and non‐NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP. CONCLUSION: NP affects approximately one‐tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients.


EDITORIAL


POSTER PRESENTATION


AETIOLOGY OF COMMUNITY ACQUIRED PNEUMONIA WITH FEVER AND THE PRESENTATION AND PROGNOSIS OF VIRAL INFECTION: A PROSPECTIVE OBSERVATIONAL STUDY


title: Viruses and autoimmunity: an affair but not a marriage contract

text: Viruses are considered as causative agents and contributors to lesion expression in autoimmune disease, notions best supported by studies in animal model systems. This review discusses relationships between virus infection and autoimmunity focusing on mechanisms by which they could induce autoreactivity. The popular idea of molecular mimicry is viewed skeptically with the reviewers taking the viewpoint that viruses contribute to autoimmunity mainly by inducing several nonspecific inflammatory events that together are sufficient to trigger autoreactivity in genetically receptive hosts. Copyright © 2002 John Wiley & Sons, Ltd.


title: Loop mediated isothermal amplification (LAMP): a new generation of innovative gene amplification technique; perspectives in clinical diagnosis of infectious diseases

text: Loop mediated isothermal amplification (LAMP) is a powerful innovative gene amplification technique emerging as a simple rapid diagnostic tool for early detection and identification of microbial diseases. The whole procedure is very simple and rapid wherein the amplification can be completed in less than 1 h under isothermal conditions employing a set of six specially designed primers spanning eight distinct sequences of a target gene, by incubating all the reagents in a single tube. Gene amplification products can be detected by agarose gel electrophoresis as well as by real‐time monitoring in an inexpensive turbidimeter. Gene copy number can also be quantified with the help of a standard curve generated from different concentrations of gene copy number plotted against time of positivity with the help of a real‐time turbidimeter. Alternatively, gene amplification can be visualised by the naked eye either as turbidity or in the form of a colour change when SYBR Green I, a fluorescent dsDNA intercalating dye, is employed. LAMP does not require a thermal cycler and can be performed simply with a heating block and/or water bath. Considering the advantages of rapid amplification, simple operation and easy detection, LAMP has potential applications for clinical diagnosis as well as surveillance of infectious diseases in developing countries without requiring sophisticated equipment or skilled personnel. Copyright © 2008 John Wiley & Sons, Ltd.


title: Saffold virus, an emerging human cardiovirus

text: Saffold virus (SAFV) is an emerging human cardiovirus that has been shown to be ubiquitous. Initial studies of SAFV focused on respiratory and gastrointestinal infection; however, it has also recently been associated with diverse clinical symptoms including the endocrine, cardiovascular, and neurological systems. Given the systemic nature of SAFV, and its high prevalence, understanding its pathogenicity and clinical impact is of utmost importance. This comprehensive review highlights and discusses recent developments in epidemiology, human pathogenicity, animal, and molecular studies related to SAFV. It also provides detailed insights into the neuropathogenicity of SAFV. We argue that human studies have been confounded by coinfections and therefore require support from robust molecular and animal research. Thereby, we aim to provide foresight into further research to better understand this emerging virus.


title: Restoration Practices Have Positive Effects on Breeding Bird Species of Concern in the Chihuahuan Desert

text: Woody plant encroachment into grasslands is a global concern. Efforts to restore grasslands often assume that removal of woody plants benefits biodiversity but assumptions are rarely tested. In the Chihuahuan Desert of the Southwestern United States, we tested whether abundances of grassland specialist bird species would be greater in plant communities resulting from treatment with herbicides to remove encroaching shrubs compared with untreated shrub‐dominated areas that represented pre‐treatment conditions. In 2010, we surveyed breeding birds and vegetation at 16 treated–untreated pairs. In 2011, we expanded the survey effort to 21 treated–untreated pairs, seven unpaired treatment areas, and five reference grassland areas. Vegetation in treatment areas had higher perennial grass foliar and basal cover and lower shrub foliar cover compared with untreated areas. Several regionally declining grassland specialists exhibited higher occurrence and relative abundance in treated areas. A shrubland specialist, however, was associated with untreated areas and may be negatively impacted by shrub removal. Bird community composition differed between treated and untreated areas in both years. Our results indicate that shrub removal can have positive effects on grassland specialist bird species, but that a mosaic of treated and untreated areas might be most beneficial for regional biodiversity.


Abstracts for the 9th Congress of the Asian Pacific Society of Respirology 10‐13 December, Hong Kong


COPD SIG: Poster Session 2


title: Borna disease virus

text: Borna disease virus (BDV) is unique amongst animal RNA viruses in its molecular biology and capacity to cause persistent, noncytolytic CNS‐infection in a wide variety of host species. Unlike other non‐segmented negative‐strand RNA animal viruses, BDV replicates in the nucleus of the host cell where splicing is employed for expression of a very compact genome. Epidemiological studies indicate a broad host range and geographical distribution, and some investigators have proposed that human infection may result in neuropsychiatric disorders. Experimental Borna disease in neonatal and adult rats provides an intriguing model for immune‐mediated disturbances of brain development and function. Copyright © 2001 John Wiley & Sons, Ltd.


title: Characterizing degradation products of peptides containing N‐terminal Cys residues by (off‐line high‐performance liquid chromatography)/matrix‐assisted laser desorption/ionization quadrupole time‐of‐flight measurements

text: A transformation analogous to the well‐known conversion of an N‐terminal glutamine residue to pyroglutamic acid is the cyclization of an N‐terminal carboxamidomethylated cysteine residue (the normal product of alkylation with iodoacetamide). This yields 5‐oxothiomorpholine‐3‐carboxylic acid, with the same 17 Da mass loss observed in the Gln reaction. Nineteen tryptic peptides with Cys at the N‐terminal were identified for this study, and compared with eight with N‐terminal Gln. When examined by MALDI‐QqTOF and (off‐line HPLC)/MALDI‐QqTOF measurements, these were all found to undergo the cyclization reactions. The average degree of degradation during overnight digestion was found to be ∼51 and ∼34% for Cys and Gln, respectively; more detailed information on the time course of the reactions was obtained for the peptides CCTESLVNR and QYYTVFDR. Taking this modification into account while sequencing is likely to increase the probability of protein identification by peptide mass fingerprinting, especially for cysteine‐rich proteins. Copyright © 2003 John Wiley & Sons, Ltd.


Paediatric SIG: Poster Session


1‐E3: COPD 4


TSANZ Oral Presentations


Invited Speakers


title: The Effect of Mask Use on the Spread of Influenza During a Pandemic

text: Face masks have traditionally been used in general infection control, but their efficacy at the population level in preventing transmission of influenza viruses has not been studied in detail. Data from published clinical studies indicate that the infectivity of influenza A virus is probably very high, so that transmission of infection may involve low doses of virus. At low doses, the relation between dose and the probability of infection is approximately linear, so that the reduction in infection risk is proportional to the reduction in exposure due to particle retention of the mask. A population transmission model was set up to explore the impact of population‐wide mask use, allowing estimation of the effects of mask efficacy and coverage (fraction of the population wearing masks) on the basic reproduction number and the infection attack rate. We conclude that population‐wide use of face masks could make an important contribution in delaying an influenza pandemic. Mask use also reduces the reproduction number, possibly even to levels sufficient for containing an influenza outbreak.


title: Effects of Surface Material, Ventilation, and Human Behavior on Indirect Contact Transmission Risk of Respiratory Infection

text: 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.


title: Pathogen inactivation/reduction of platelet concentrates: turning theory into practice

text: Background Pathogen reduction technology (PRT) has been proven to reduce the residual risk of transmission of infectious agents. Reduction of various contaminating bacteriae, viruses and parasites by few to several log steps and efficiency to prevent GVHD has been shown. Aim To evaluate and compare advantages and disadvantages of PRT available for practical application in platelets. Materials and Methods PRT for the treatment of platelets is currently offered by two formats: Amotosalen (INTERCEPT, Cerus, Concord, CA, USA) and vitamin B2 (Mirasol, Caridian, Denver, USA). Results from different studies and our own experiences with the two techniques are compared and discussed. Results and Discussion For both technologies, different groups of investigators have shown acceptable in‐vitro results with respect to functional and storage data for platelets stored for up to 5 days after production and before transfusion. Initial clinical studies showed no inferiority of the treated platelets in comparison to untreated controls in thrombocytopenic patients. However for both techniques a tendency towards lower CCI has been reported, which may be more pronounced in the platelets treated with the Intercept process. For introduction of PRT many countries require not only CE mark but licensing with the respective authorities since treatment for pathogen reduction is regarded as creating a ‘new’ blood product. With respect to a platelet loss during pathogen reduction it seems recommendable to increase the lower limit of platelet content of the product to 2.5 × 10(11). Particularly for the Intercept system, where a considerable amount of platelets is lost in the purification of the product from Amotosalen, a change in the production process to increase the platelet yield may be necessary. Data from our group show a tendency for improved functional and storage parameters for platelets treated with the Mirasol process. Compared to conventional manufacturing of platelets by apheresis or pooling of buffy coats, pathogen reduction requires additional labour, space, and quality control. Shelf life of platelets is limited in most countries because of the risk of bacterial contamination (in Germany presently to 4 days). A prolongation to 5 or more days after pathogen reduction seems feasible but remains a topic for future studies. Conclusion Results of in vitro and clinical studies of pathogen reduced platelets are promising. Larger clinical trials will help to determine whether PRT proves to be beneficial (reduction of transmission of infections, less alloimmunisation) and overall cost effective (bearing in mind that additional costs may be compensated for by omission of gamma irradiation and potential longer shelf life).


title: Serum Lipase Activity in Young Dogs With Acute Enteritis or Gastroenteritis

text: Blood serum lipase activity was determined in 48 young dogs with acute enteritis or gastroenteritis due to canine parvovirus (16 cases) and presumably to other infectious agents (32 cases). Elevated serum lipase activity (> 500 U/L) was found in 13 dogs (27.1%) with values ranging from 800 to 2,780 U/L. The hyperlipasemia of these cases may be attributed to acute pancreatitis secondary to acute gastroenteritis or to gastrointestinal upset.


Print‐only Abstracts


Threats to blood safety posed by emerging protozoan pathogens


title: ULTRASONOGRAPHIC AND PATHOLOGIC FEATURES OF INTESTINAL SMOOTH MUSCLE HYPERTROPHY IN FOUR CATS

text: The ultrasonographic findings for four cats with intestinal smooth muscle hypertrophy are described. In two cats, intestinal smooth muscle hypertrophy was associated with chronic enteritis. In the remaining two cats, intestinal smooth muscle hypertrophy affected the intestinal tract proximal to stenosis due to alimentary lymphoma and an intestinal foreign body, respectively. Moderate increased thickness of the affected intestinal wall, measuring 7–8 mm, was evident on abdominal ultrasonographic examination of all subjects. In addition, the ultrasonographic five‐layered feature of the intestinal wall was maintained, and only the muscular layer appeared thickened. Abdominal ultrasound allowed a presumptive diagnosis of intestinal smooth muscle hypertrophy that was confirmed histologically in all cats.


title: Globalization and blood safety

text: Globalization may be viewed as the growing interdependence of countries worldwide through the increasing volume and variety of cross‐border transactions in goods and services, and also through the more rapid and widespread diffusion of technology. Globalization is not just an economic phenomenon, although it is frequently described as such, but includes commerce, disease and travel, and immigration, and as such it affects blood safety and supply in various ways. The relatively short travel times offered by modern aviation can result in the rapid spread of blood‐borne pathogens before measures to counteract transmission can be put in place; this would have happened with SARS if the basic life cycle of the SARS virus did not include an asymptomatic viraemia. This risk can be amplified by ecological factors which effect the spread of these pathogens once they are transferred to a naïve ecosystem, as happened with West Nile virus (WNV) in North America. The rationalization and contraction of the plasma products industry may be viewed as one aspect of globalization imposed by the remorseless inevitability of the market; the effect of this development on the safety and supply of products has yet to be seen, but the oversight and assurance of a shrinking number of players will present particular challenges. Similarly, the monopolization of technology, through patent enforcement which puts access beyond the reach of developing countries, can have an effect on blood safety. The challenges presented to blood safety by globalization are heightening the tensions between the traditional focus on the product safety – zero‐risk paradigm and the need to view the delivery of safe blood as an integrated process. As an illustration of this tension, donor deferral measures imposed by globalization‐induced risks such as vCJD and WNV have resulted in the loss of the safest and most committed portion of the blood donor population in many Western countries, leading to an increased risk to safety and supply. It is only through an appreciation of the basic needs of transfusion medicine, including the enunciation of appropriate principles to manage, rather than eliminate, risks, that the challenges imposed by globalization may be overcome.


title: CONTRAST‐ENHANCED ULTRASONOGRAPHY OF THE SMALL BOWEL IN HEALTHY CATS

text: We characterized the pattern of ultrasonographic contrast enhancement of the small intestinal wall using a commercial contrast medium (Sonovue(®)) in 10 healthy awake cats. Subjectively, a rapid intense enhancement of the serosal and submucosal layers was followed by gradual enhancement of the entire wall section during the early phase. At peak enhancement, there was a subjective loss of demarcation between intestinal wall layers. In the late phase, there was a gradual wash out of signal from the intestinal wall. Submucosal wash out occurred last. Time‐intensity curves were generated for selected regions in the intestinal wall and multiple perfusion parameters were calculated for each cat. Perfusion parameters included arrival time (7.64 ± 2.23 s), baseline intensity (1.04 ± 0.04 a.u.), time to peak from injection (10.74 ± 2.08 s), time to peak from initial rise (3.1 ± 1.15), peak intensity (8.92 ± 3.72 a.u.), wash‐in rate (2.06 ± 0.70 a.u./s) and wash‐out rate (−1.07 ± 0.91 a.u./s). The perfusion pattern of normal feline small bowel may be useful for characterizing feline gastrointestinal disorders that involve the intestinal wall.


Oral Abstracts


Oral abstracts


ABSTRACTS FROM THE 2014 EUROPEAN VETERINARY DIAGNOSTIC IMAGING ANNUAL CONFERENCE: Utrecht, The Netherlands, August 27 – August 30, 2014


title: MAGNETIC RESONANCE IMAGING OF THE NORMAL AND DISEASED FELINE MIDDLE EAR

text: The magnetic resonance imaging appearance of the feline middle ear is described in three healthy cats and in five cats with middle ear disease. Owing to the good spatial resolution, multiplanar slice orientation as well as display high contrast resolution of soft tissue, in particular fluids, MR imaging was helpful prior to surgery. It is superior to radiography which failed to allow identification of the abnormality in two of our five cats. MR imaging for middle ear disease should include dorsal and transverse plane images using T1‐ and T2‐ weighted sequences. In the presence of a mass within the bulla or the external ear canal application of contrast medium is helpful.


Abstract of 29th Regional Congress of the ISBT


This won't hurt …: Tiny needles deliver drugs painlessly


Environment: Toxic cleanups get a boost


Biomedicine: Acid blockers stop stomach ulcers, too


title: Unbuttoning normalcy – on cosmopolitical events

text: The history of social research can be read as a critical endeavour inasmuch as it unbuttons the normalcy of collective action by multiplying relevant actors and the imaginaries of social reality. I show how paying close sociological attention to what I call cosmopolitical events, offers one approach to such a conception of critical social science. In the paper, I explore the effects of the Japanese events at the Fukushima nuclear plant to unfold its significance as consequences that disrupt, question and alter common and taken for granted modes of ordering social life. Specifically, through approaching Fukushima as a cosmopolitical event we gain insight into the complex processes of normalizing social relations. Moreover, the Fukushima event and its effects demand to extend the history of the sociological imagination to the social and political relevance of the non‐human. What emerges is a practice that enriches the process of unfolding research agendas and conceptual space to include those that have been excluded, marginalized, forgotten, unconsidered, or disfigured in the process of normalizing social and political action.


Out of China: SARS virus' genome hints at independent evolution


Biomedicine: SARS vaccine triggers immunity in monkeys


Electronic thread: Fiber transistor may lead to woven circuits


Environment: When testosterone gets down and dirty


Vaccines: Kids' vaccine guards adults too, for now


title: Evaluating the ALERT algorithm for local outbreak onset detection in seasonal infectious disease surveillance data

text: Estimation of epidemic onset timing is an important component of controlling the spread of seasonal infectious diseases within community healthcare sites. The Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm uses a threshold‐based approach to suggest incidence levels that historically have indicated the transition from endemic to epidemic activity. In this paper, we present the first detailed overview of the computational approach underlying the algorithm. In the motivating example section, we evaluate the performance of ALERT in determining the onset of increased respiratory virus incidence using laboratory testing data from the Children's Hospital of Colorado. At a threshold of 10 cases per week, ALERT‐selected intervention periods performed better than the observed hospital site periods (2004/2005–2012/2013) and a CUSUM method. Additional simulation studies show how data properties may effect ALERT performance on novel data. We found that the conditions under which ALERT showed ideal performance generally included high seasonality and low off‐season incidence.


title: A revision of the western Palaearctic species of Urophora Robineau‐Desvoidy (Diptera: Tephritidae)

text: Abstract A key is provided to twenty‐four western Palaearctic species of Urophora Robineau‐Desvoidy. The hosts of twenty‐three species which attack Asteraceae are listed, including those being used or investigated as possible weed biocontrol agents. The species are divided into four species groups and the differing host relationships and types of galls induced by these groups are discussed. U.lopholomae sp.n. and U.affinis ssp. calcitrapae ssp.n., associated with Centaurea (Lopholoma) spp. and C. (Calcitrapa) spp. respectively, are described. U. algerica (Hering) and U.sjumorum (Rohdendorf) are both treated as subspecies of U. quadrifasciata (Meigen). U.pontica is given full specific status and U.hispanica is removed from synonymy. The following new synonymies are made (junior synonyms in parentheses): U. angustifascia (Hering) (=Euribia phaeocera Hering); U. cardui (Linnaeus) (=U. reaumurii Robineau‐Desvoidy, lectotype designated); U. jaceana (Hering) (=E.conyzae Hering); U.maura (Frauenfeld) (=E. tecta Hering); U. mauritanica Macquart (=U. lejura Rondani, Trypeta macrura Loew); U.solstitialis (Linnaeus) (=E.sonderupi Hering, U. veruata Rondani); U.stylata (Fabricius) (=E.pia Hering, U. vulcaanica Rondani); U. terebrans (Loew) (=E. approximata Hering, T. eriolepidis Loew, E. manni Hendel). The possibility that U. quadrifasciata is a species complex is discussed; it is also suggested that U.affinis and U.jaceana represent the morphological extremes of a complex. The misuse of the name Musca stylata Fabricius in the genus Myopites Blot is noted.


title: Identification and discrimination of Electrogena species by numerical methods (Ephemeroptera: Heptageniidae)

text: Abstract. Nine species of Electrogena from thirty‐one populations were investigated on the basis of five meristic and five ratio characters of the larvae. The attribution of populations to species was checked by a cluster analysis based on the generalized distances between pairs. Groups representing species were then subjected to a multiple discriminant analysis; discriminant functions and loadings were calculated. The correct attribution of individuals to species by the discriminant functions ranged from 97% to 100%. The analysis of discriminant loadings shows which characters contribute more to the discrimination of species. Although many species could be identified with some confidence by a sequential monothetic key based on meristic and qualitative characters, the discriminant analysis improves the effectiveness of identification of all species.


Biomedicine: SARs virus can spread in lab animals


title: Phylogeny and classification of the Signiphoridae (Hymenoptera: Chalcidoidea)

text: Abstract. A data set consisting of twenty‐eight anatomical characters scored for twenty‐eight terminal taxa representing the world fauna of Signiphoridae was analysed using parsimony and compatibility methods. The Coccophaginae (Aphelinidae) and the Azotinae (Aphelinidae) were used as outgroups to establish polarity of character state changes. Relationships of Signiphoridae to other Chalcidoidea are discussed. Several multistate characters were treated in the parsimony analyses either as unordered or as ordered into transformation series using additive binary coding, which in some cases drastically reduced the number of equally parsimonious solutions. Monophyly of Signiphoridae is supported by seven synapomorphies. Four genera, Chartocerus, Thysanus, Clytina and Signiphora, are recognized within Signiphoridae based on synapomorphies. Rozanoviella syn.n. and Kerrichiella syn.n. are synonymized under Signiphora. Species of Signiphora are further assigned to four species groups, three of which are demonstrably monophyletic. Nine species or subspecies are transferred to Chartocerus from Signiphora (australicus comb.n., australiensis comb.n., australiensis orbiculatus comb.n., beethoveni comb.n., corvinus comb.n., funeralis comb.n., reticulata comb.n., ruskini comb.n., thusanoides comb.n.), one species to Thysanus from Signiphora (melancholicus comb.n.), and one species to Signiphora from Kerrichiella (coleoptratus comb.n.). A key to genera of Signiphoridae and species groups of Signiphora is presented. A diagnosis, relevant nomenclatural history, and a list of included species are given for each genus and species group, and the biology and distribution of each is summarized.


Astronomy: X‐ray images highlight galaxy collisions


Biomedicine: Human antibody halts SARS in hamsters


Books for late summer: From genius genes to tyrannosaur musings


Fine toothcomb: New fossils add to primate‐origins debate


Emerging pathogens: Drug‐resistant staph causes more pneumonia


The next MTBE: Contamination from fuel additives could spread


title: A Nanostructured Microfluidic Immunoassay Platform for Highly Sensitive Infectious Pathogen Detection

text: Rapid and simultaneous detection of multiple potential pathogens by portable devices can facilitate early diagnosis of infectious diseases, and allow for rapid and effective implementation of disease prevention and treatment measures. The development of a ZnO nanorod integrated microdevice as a multiplex immunofluorescence platform for highly sensitive and selective detection of avian influenza virus (AIV) is described. The 3D morphology and unique optical property of the ZnO nanorods boost the detection limit of the H5N2 AIV to as low as 3.6 × 10(3) EID(50) mL(−1) (EID(50): 50% embryo infectious dose), which is ≈22 times more sensitive than conventional enzyme‐linked immunosorbent assay. The entire virus capture and detection process could be completed within 1.5 h with excellent selectivity. Moreover, this microfluidic biosensor is capable of detecting multiple viruses simultaneously by spatial encoding of capture antibodies. One prominent feature of the device is that the captured H5N2 AIV can be released by simply dissolving ZnO nanorods under slightly acidic environment for subsequent off‐chip analyses. As a whole, this platform provides a powerful tool for rapid detection of multiple pathogens, which may extent to the other fields for low‐cost and convenient biomarker detection.


Bacterial ecology: New bacteria linked to vaginal infections


title: Significance of new lung infiltrates in outpatients after lung and heart–lung transplantation

text: BACKGROUND: Infection and rejection represent major complications following lung transplantation and are often associated with pulmonary infiltrates. The differential diagnosis of these infiltrates depends on their timing after transplantation. The aim of this study was to characterize lung transplant recipients (LTR) presenting with new pulmonary infiltrates. METHODS: A retrospective analysis of all LTR and heart–lung transplant recipients attending outpatient follow‐up at our institution between September 1, 2006 and October 14, 2011 was performed. All patients presenting with new pulmonary infiltrates on chest x‐ray who underwent bronchoscopy were included. RESULTS: A total of 913 patients accounted for 13,156 attendances, with 3,912 bronchoscopies being performed. Seventy‐eight patients (9%) exhibited new pulmonary infiltrates and proceeded to bronchoscopy. Infiltrates occurred at a median 15 (interquartile range [IQR] 5–39) months after transplantation. Forty‐eight patients (62%) were male, and median patient age was 47 (IQR 29–57) years. Subsequent investigation revealed pneumonia to be the underlying cause in 63 patients (81%). In the remaining patients, chronic lung allograft dysfunction (CLAD) was responsible in 6 (8%), acute rejection in 5 (6%), and toxic pneumonitis in 4 (5%) patients. Overall 1‐year survival in LTR presenting with new infiltrates was 97%, compared with 96% for all LTR attending our Outpatient Department. CONCLUSIONS: New pulmonary infiltrates occurring after the first month in LTR are most likely due to infection. Through prompt diagnosis and treatment, early mortality appears unaffected. Late mortality remains attributable to CLAD.


Scientific Section


title: Hepatitis E Virus and Related Viruses in Animals

text: Hepatitis E is an acute human liver disease in healthy individuals which may eventually become chronic. It is caused by the hepatitis E virus (HEV) and can have a zoonotic origin. Nearly 57,000 people die yearly from hepatitis E‐related conditions. The disease is endemic in both developing and developed countries with distinct epidemiologic profiles. In developing countries, the disease is associated with inadequate water treatment, while in developed countries, transmission is associated with animal contact and the ingestion of raw or uncooked meat, especially liver. All human HEV are grouped into at least four genotypes, while HEV or HEV‐related viruses have been identified in an increasing number of domestic and wild animal species. Despite a high genetic diversity, only one single HEV serotype has been described to date for HEV genotypes 1–4. The discovery of new HEV or HEV‐related viruses leads to a continuing increase in the number of genotypes. In addition, the genome organization of all these viruses is variable with overlapping open reading frames (ORF) and differences in the location of ORF3. In spite of the role of some domestic and wild animals as reservoir, the origin of HEV and HEV‐related viruses in humans and animals is still unclear. This review discusses aspects of the detection, molecular virology, zoonotic transmission and origin of HEV and HEV‐related viruses in the context of ‘One Health’ and establishes a link between the previous and the new taxonomy of this growing virus family.


Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017


title: Ribosomal frameshifting in yeast viruses

text: Proper maintenance of translational reading frame by ribosomes is essential for cell growth and viability. In the last 10 years it has been shown that a number of viruses induce ribosomes to shift reading frame in order to regulate the expression of gene products having enzymatic functions. Studies on ribosomal frameshifting in viruses of yeast have been particularly enlightening. The roles of viral mRNA sequences and secondary structures have been elucidated and a picture of how these interact with host chromosomal gene products is beginning to emerge. The efficiency of ribosomal frameshifting is important for viral particle assembly, and has identified ribosomal frameshifting as a potential target for antiviral agents. The availability of mutants of host chromosomal gene products involved in maintaining the efficiency of ribosomal frameshifting bodes well for the use of yeast in future studies of ribosomal frameshifting.


title: Relationships between Floodplain Lake Fish Communities and Environmental Variables in a Large River‐Floodplain Ecosystem

text: Floodplain lakes of large river systems contain fish habitats that are not found elsewhere within the river, and these lakes have a diversity of environmental conditions that vary in space and time. Our objective was to examine relationships between floodplain lake fish communities and environmental variables associated with lake morphology, water chemistry, and river‐floodplain connectivity in a large river‐floodplain ecosystem. Multivariate direct‐gradient analyses indicated that lake surface area, lake depth, water clarity, and (to a lesser extent) dissolved oxygen were the most important factors in the structuring of lake fish communities. Results further suggested that floodplain lakes could be placed into groups that contained distinctive fish communities. Fish community structure was not strongly related to river‐floodplain connectivity, though fish species richness in individual lakes was positively correlated with degree of flooding in those lakes. Fish species diversity in lakes was positively correlated with linear distance between lakes and the main river channel; lakes that were furthest from the main river channel had more diverse fish communities. The diversity of environmental conditions in floodplain lakes is essential for maintaining net ecosystem diversity in large river ecosystems.


Viral attacks on the blood supply: the impact of severe acute respiratory syndrome in Beijing


title: Infectivity of Cryptosporidium parvum oocysts is retained upon intestinal passage through a migratory water‐fowl species (Canada goose, Branta canadensis)

text: Summary Five Cryptosporidium‐free Canada geese (Branta canadensis) were individually orally dosed with 3–5 × 10(6) Cryptosporidium parvum oocysts infectious to neonatal BALB/c mice. After intestinal passage, inoculum‐derived oocysts extracted from goose faeces established severe infection in 14 neonatal BALB/c mice (inoculum dose 2.5 × 10(5)/mouse). The inoculum‐derived oocysts were detected in goose faeces up to 9 days post‐inoculation (PI); the number of intact oocysts and oocyst shells shed during the first 3 days PI was significantly higher than for the remaining 6 days PI (P<0.01). Based on acid‐fast stained air‐dried direct wet smears, 62% of the oocysts in goose faeces were intact (oocyst shells constituted 38%) and conformed to morphological features of viable and infectious inoculum oocysts. The fluorescence scores of the inoculated oocysts, obtained by use of the MERIFLUOR test, were identical to those obtained for the faeces‐recovered oocysts (majority 3 + to 4 +). The dynamics of oocyst shedding showed that overall, the birds released a significantly higher number of intact oocysts than oocyst shells (P<0.01) Retention of the viability and infectivity of C. parvum oocysts following intestinal passage through a migratory water‐fowl species has serious epidemiological implications. Water‐fowl can serve as mechanical vectors for the water‐borne oocysts and can contaminate surface waters with C. parvum. As the concentration of Cryptosporidium oocysts in source waters is attributable to water‐shed management practices, water‐shed protection programme officials should consider water‐fowl as a potential factor enhancing contamination of the source water with Cryptosporidium.


Abstracts of the Joint Conference of the Canadian Society for Transfusion Medicine, Canadian Blood Services and Héma‐Québec, Banff, Alberta, Canada, 21–24 April 2005


title: Classification of Texas Reservoirs in Relation to Limnology and Fish Community Associations

text: I used cluster analysis to examine associations among 20 fish species to develop a classification scheme for 132 large Texas reservoirs. Five major groups of reservoirs were identified by cluster analysis based on species associations. Of 29 reservoirs surveyed previously, 76% were classified into the same species associations from one survey to the next. When 19 environmental variables were used in canonical correlation analysis of the five reservoir groups, I found a general east‐to‐west separation of species associations by water quality and a northwest‐to‐southeast separation by surface elevation and growing season. A discriminant functions model based on a reduced set of nine environmental variables had an unbiased error rate of 18% for predicting the species association in unclassified reservoirs. A stratified sampling scheme based on the classification model decreased the variance of statewide electrofishing catch per effort up to 43% for bluegill Lepomis macrochirus and 23% for largemouth bass Micropterus salmoides over a simple random sample of reservoirs.


title: Molecular delimitation of clades within New World species of the "spiny solanums" (Solanum subg. Leptostemonum)

text: Solanum subg. Leptostemonum contains approximately 350–450 species, including the cultivated eggplant, S. melongena. Most species placed in this subgenus form a monophyletic group, the Leptostemonum clade, characterized by the presence of stellate hairs and prickles, leading to the common name of "spiny solanums". Here we present a phylogenetic analysis that circumscribes the major clades within the spiny solanums and examines the relationships among them, with an emphasis on New World species. Of particular interest is the clarification of the clade limits and species composition of groups that have not been well‐sampled. We also increase sampling of taxa that have been previously analyzed in molecular studies, namely those in the Torva, Micracantha, and Erythrotrichum clades. These groups have convergent morphological characteristics that have challenged taxonomists, making classification difficult. Results from our study delimit 14 clades within the spiny solanums, including the newly designated Asterophorum, Gardneri, Sisymbriifolium, and Thomasiifolium clades. We also establish the placement of species not previously sampled, especially those endemic to Brazil. These results give an increased understanding of the evolution of the Leptostemonum clade by defining monophyletic groups within it and identify areas of the phylogenetic tree that remain unresolved and require further taxon sampling.


Tempering the risk: Rift Valley fever and bioterrorism


title: Seasonal Diversity, Abundance, and Distribution of Ichthyoplankton in Tamiahua Lagoon, Western Gulf of Mexico

text: The ichthyoplanktonic community of Tamiahua Lagoon, Veracruz, Mexico, was studied throughout an annual cycle. Major concentrations of larvae occurred in the central portion of the lagoon, occasionally along the channels, but never at the inlets. The cycle of larva abundance was correlated with cycles of salinity and temperature. In spite of the greater number of species then, the spring and summer periods had low species diversity and evenness, due to the marked domination by larvae of Anchoa mitchilli. The number of larval fish species and individuals entering the lagoon from the adjacent offshore waters was minimal. The greatest portion of species diversity is generated within the lagoon itself. The community structure identified corresponds to the physically controlled type, as indicated by the poor diversity values obtained.


title: Infections after T‐replete haploidentical transplantation and high‐dose cyclophosphamide as graft‐versus‐host disease prophylaxis

text: BACKGROUND: Recently, a platform of T‐cell replete haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) using post‐transplant cyclophosphamide (Cy) has shown high reproducibility and acceptable safety profile. METHOD: This prospective cohort analysis allowed us to collect data on infections among 70 consecutive recipients of haplo‐HSCT affected by various hematologic malignancies. RESULTS: After a median follow‐up of 23 months, cumulative incidence of viral infections was 70% (95% confidence interval [CI] 59–81) at 100 days and 77% (95% CI 67–87) at 1 year; 35 of 65 patients at risk had CMV reactivation (54%) and the rate of polyomavirus‐virus‐associated cystitis was 19% (13/70). Cumulative incidence of bacterial and fungal infections at 1 year were 63% (95% CI 51–75) and 12% (95% CI 4–19), respectively. Of note, only 1 invasive fungal infection occurred beyond 1 year after transplant (day +739). CONCLUSION: In conclusion, despite a high rate of viral infections in the early period, present data suggest a satisfactory infectious profile after T‐cell replete haplo‐HSCT using post‐transplant Cy. These results may help clinicians to improve both prophylactic and therapeutic antimicrobial strategies in this emerging haploidentical setting.


title: Design, Synthesis, and Evaluation of Bioactive Small Molecules

text: Collaborative research projects between chemists, biologists, and medical scientists have inevitably produced many useful drugs, biosensors, and medical instrumentation. Organic chemistry lies at the heart of drug discovery and development. The current range of organic synthetic methodologies allows for the construction of unlimited libraries of small organic molecules for drug screening. In translational research projects, we have focused on the discovery of lead compounds for three major diseases: Alzheimer's disease (AD), breast cancer, and viral infections. In the AD project, we have taken a rational‐design approach and synthesized a new class of tricyclic pyrone (TP) compounds that preserve memory and motor functions in amyloid precursor protein (APP)/presenilin‐1 (PS1) mice. TPs could protect neuronal death through several possible mechanisms, including their ability to inhibit the formation of both intraneuronal and extracellular amyloid β (Aβ) aggregates, to increase cholesterol efflux, to restore axonal trafficking, and to enhance long‐term potentiation (LTP) and restored LTP following treatment with Aβ oligomers. We have also synthesized a new class of gap‐junction enhancers, based on substituted quinolines, that possess potent inhibitory activities against breast‐cancer cells in vitro and in vivo. Although various antiviral drugs are available, the emergence of viral resistance to existing antiviral drugs and various understudied viral infections, such as norovirus and rotavirus, emphasizes the demand for the development of new antiviral agents against such infections and others. Our laboratories have undertaken these projects for the discovery of new antiviral inhibitors. The discussion of these aforementioned projects may shed light on the future development of drug candidates in the fields of AD, cancer, and viral infections.


Oral Presentation Sessions


title: Targeting of the Hydrophobic Metabolome by Pathogens

text: The hydrophobic molecules of the metabolome – also named the lipidome – constitute a major part of the entire metabolome. Novel technologies show the existence of a staggering number of individual lipid species, the biological functions of which are, with the exception of only a few lipid species, unknown. Much can be learned from pathogens that have evolved to take advantage of the complexity of the lipidome to escape the immune system of the host organism and to allow their survival and replication. Different types of pathogens target different lipids as shown in interaction maps, allowing visualization of differences between different types of pathogens. Bacterial and viral pathogens target predominantly structural and signaling lipids to alter the cellular phenotype of the host cell. Fungal and parasitic pathogens have complex lipidomes themselves and target predominantly the release of polyunsaturated fatty acids from the host cell lipidome, resulting in the generation of eicosanoids by either the host cell or the pathogen. Thus, whereas viruses and bacteria induce predominantly alterations in lipid metabolites at the host cell level, eukaryotic pathogens focus on interference with lipid metabolites affecting systemic inflammatory reactions that are part of the immune system. A better understanding of the interplay between host–pathogen interactions will not only help elucidate the fundamental role of lipid species in cellular physiology, but will also aid in the generation of novel therapeutic drugs. [Image: see text]


title: Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation

text: BACKGROUND: Red blood cell (RBC) transfusion risks could be reduced if a robust technology for pathogen inactivation of RBC (PI‐RBCs) were to be approved. MATERIALS AND METHODS: Estimates of per‐unit and per‐patient aggregate infectious risks for conventional RBCs were calculated; the latter used patient diagnosis as a determinant of estimated lifetime exposure to RBC units. Existing in vitro data for the two technologies under development for producing PI‐RBCs and the status of current clinical trials are reviewed. RESULTS: Minimum and maximum per‐unit risk were calculated as 0.0003% (1 in 323,000) and 0.12% (1 in 831), respectively. The minimum estimate is for known lower‐risk pathogens while the maximal estimate also includes an emerging infectious agent (EIA) and endemic area Babesia risk. Minimum and maximum per‐patient lifetime risks by diagnosis grouping were estimated as 1.5 and 3.3%, respectively, for stem cell transplantation (which includes additional risk for cytomegalovirus transmission); 1.2 and 3.7%, respectively, for myelodysplastic syndrome; and 0.2 and 44%, respectively, for hemoglobinopathy. DISCUSSION: There is potential for PI technologies to reduce infectious RBC risk and to provide additional benefits (e.g., prevention of transfusion‐associated graft‐versus‐host disease and possible reduction of alloimmunization) due to white blood cell inactivation. PI‐RBCs should be viewed in the context of having a fully PI‐treated blood supply, enabling a blood safety paradigm shift from reactive to proactive. Providing insurance against new EIAs. Further, when approved, the use of PI for all components may catalyze operational changes in blood donor screening, laboratory testing, and component manufacturing.


Abstract Presentations from the AABB Annual Meeting Boston, MA, October 13–16, 2018


title: An approach to the control of disease transmission in pig‐to‐human xenotransplantation

text: Abstract: Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ‐source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ‐source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved.


Nosocomial Infection in the Intensive Care Unit


title: The Immunology of Bovine Respiratory Disease: Recent Advancements

text: Bovine respiratory disease (BRD) remains a leading cause of morbidity, mortality, and economic loss to the cattle industry. The continued high prevalence of the disease underlines a gap in understanding of the host immune response to respiratory infection. The host immune response is beneficial and detrimental, required for clearing the disease but often leading to tissue damage and long-term defects in lung function. This article highlights advancements made in understanding innate and adaptive immunity in BRD, factors that predispose animals to BRD, and novel intervention strategies that may lead to changes in the approach to treating and controlling BRD.


Veranstaltungstipps


title: Use of high frequency oscillatory ventilator in neonates with respiratory failure: the clinical practice in Taiwan and early multimodal outcome prediction

text: High-frequency oscillatory ventilation (HFOV) can be a rescue for neonates with refractory respiratory failure or an early elective therapy for preterm infants with severe respiratory distress syndrome (RDS). However, little is known about the current evolution and therapeutic limitations of HFOV. We therefore aimed to describe its use in clinical practice and predict the risk of mortality for neonates receiving HFOV. A retrospective observational study of all neonates treated with HFOV in a quaternary referral NICU between January 2007 and December 2016 was conducted. We classified these patients into five subgroups based on primary respiratory diagnoses. We performed the logistic regression and decision tree regression analyses to identify independent factors of 30-day mortality following HFOV. A total of 1125 patients who were ever supported on HFOV were enrolled, of whom 64.1% received HFOV as a rescue therapy, 27.2% received it as an elective therapy, and 8.7% received it for air leak. An average oxygenation index (OI) greater than 25 in the first 24 hours after the initiation of HFOV and patients with secondary pulmonary hypertension were found to have the greatest risk of in-hospital mortality (p < 0.0001). The overall in-hospital mortality rate was 25.8% (290/1125). Decision tree regression analysis revealed that neonates with refractory respiratory failure who had a pre-HFOV OI value higher than 20.5 and OI values higher than 21.5, 23.5 and 34 at 2 hours, 6 hours, and 12 hours after the use of HFOV, respectively, had a significantly increased risk of 30-day mortality. We identified the predictors and cutoff points of OI before and after the initiation of HFOV in neonates with respiratory failure, which can be clinically used as a reference for 30-day mortality. Further efforts are still needed to optimize the outcomes.


title: Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A

text: Plasmodium falciparum merozoite invasion into erythrocytes is an essential step of the blood-stage cycle, survival of parasites, and malaria pathogenesis. P. falciparum merozoite Rh5 interacting protein (PfRipr) forms a complex with Rh5 and CyRPA in sequential molecular events leading to erythrocyte invasion. Recently we described PfRipr as a conserved protein that induces strain-transcending growth inhibitory antibodies in in vitro assays. However, being a large and complex protein of 1086 amino acids (aa) with 87 cysteine residues, PfRipr is difficult to express in conventional expression systems towards vaccine development. In this study we sought to identify the most potent region of PfRipr that could be developed to overcome difficulties related to protein expression, as well as to elucidate the invasion inhibitory mechanism of anti-PfRipr antibodies. Using the wheat germ cell-free system, Ecto- PfRipr and truncates of approximately 200 aa were expressed as soluble proteins. We demonstrate that antibodies against PfRipr truncate 5 (PfRipr_5: C(720)-D(934)), a region within the PfRipr C-terminal EGF-like domains, potently inhibit merozoite invasion. Furthermore, the antibodies strongly block PfRipr/Rh5 interaction, as well as that between PfRipr and its erythrocyte-surface receptor, SEMA7A. Taken together, PfRipr_5 is a potential candidate for further development as a blood-stage malaria vaccine.


title: Nonantibiotic Adjunctive Therapies for Community-Acquired Pneumonia (Corticosteroids and Beyond): Where Are We with Them?

text: Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAP, although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAP, but more studies are needed to determine their impact on mortality.


title: Community-Acquired Pneumonia in the Asia-Pacific Region

text: Community-acquired pneumonia (CAP) is an important cause of mortality and morbidity worldwide. Aging population, dense urbanization, and poor access to health care make the Asia-Pacific region vulnerable to CAP. The high incidence of CAP poses a significant health and economic burden in this region. Common etiologic agents in other global regions including Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Staphylococcus aureus, and respiratory viruses are also the most prevalent pathogens in the Asia-Pacific region. But the higher incidence of Klebsiella pneumoniae and the presence of Burkholderia pseudomallei are unique to the region. The high prevalence of antimicrobial resistance in S. pneumoniae and M. pneumoniae has been raising the need for more prudent use of antibiotics. Emergence and spread of community-acquired methicillin-resistant S. aureus deserve attention, while the risk has not reached significant level yet in cases of CAP. Given a clinical and socioeconomic importance of CAP, further effort to better understand the epidemiology and impact of CAP is warranted in the Asia-Pacific region.


title: Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention

text: Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians.


title: Avian Influenza A Viruses: Evolution and Zoonotic Infection

text: Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics.


title: Enterovirus D68 and Human Respiratory Infections

text: Enterovirus D68 (EV-D68) is a member of the species Enterovirus D in the genus Enterovirus of the Picornaviridae family. EV-D68 was first isolated in the United States in 1962 and is primarily an agent of respiratory disease. Infections with EV-D68 have been rarely reported until recently, when reports of EV-D68 associated with respiratory disease increased notably worldwide. An outbreak in 2014 in the United States, for example, involved more than 1,000 cases of severe respiratory disease that occurred across almost all states. Phylogenetic analysis of all EV-D68 sequences indicates that the circulating strains of EV-D68 can be classified into two lineages, lineage 1 and lineage 2. In contrast to the prototype Fermon strain, all circulating strains have deletions in their genomes. Respiratory illness associated with EV-D68 infection ranges from mild illness that just needs outpatient service to severe illness requiring intensive care and mechanical ventilation. To date, there are no specific medicines and vaccines to treat or prevent EV-D68 infection. This review provides a detailed overview about our current understanding of EV-D68-related virology, epidemiology and clinical syndromes, pathogenesis, and laboratory diagnostics.


title: Human Respiratory Syncytial Virus: Infection and Pathology

text: The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host.


title: Parainfluenza Virus Infection

text: Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of the Paramyoviridaie family. There are four serotypes which cause respiratory illnesses in children and adults. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. Seasonal HPIV epidemics result in a significant burden of disease in children and account for 40% of pediatric hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup cases. Parainfluenza viruses are associated with a wide spectrum of illnesses which include otitis media, pharyngitis, conjunctivitis, croup, tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely disseminated infection. Immunity resulting from disease in childhood is incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in adults. Severe disease and fatal pneumonia may occur in elderly and immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6 months. Though sensitive molecular diagnostics are available to rapidly diagnose HPIV infection, effective antiviral therapies are not available. Currently, treatment for HPIV infection is supportive with the exception of croup where the use of corticosteroids has been found to be beneficial. Several novel drugs including DAS181 appear promising in efforts to treat severe disease in immunocompromised patients, and vaccines to decrease the burden of disease in young children are in development.


title: Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

text: Among immunocompromised individuals, members of the human Herpesviridae family are frequently encountered pathogens. Cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, Epstein–Barr virus, and human herpesvirus-6, -7, and -8 all establish latency after infection and can reactivate during periods of immunosuppression, leading to both direct and indirect adverse effects on the host including severe organ dysfunction as well as allograft rejection and loss after transplantation. While not all herpesviruses are primary respiratory pathogens, many of their manifestations include involvement of the respiratory tract. This article discusses the individual viruses, their epidemiology, and clinical manifestations as well as recommended treatment and preventive strategies.


title: Phylogeography and genetic diversity of the copepod family Cyclopidae (Crustacea: Cyclopoida) from freshwater ecosystems of Southeast Nigeria

text: BACKGROUND: Copepods are key components of aquatic ecosystems and can help regulate the global carbon cycle. Much attention has been paid to the species diversity of copepods worldwide, but the phylogeography and genetic diversity of copepods in Nigeria is unexplored. RESULTS: Using a mitochondrial cytochrome c oxidase subunit I marker, we preformed phylogenetic and phylogeographic analyses for Cyclopidae copepods in Southeast Nigeria. A high species diversity of Cyclopidae in Nigeria: 5 species of Tropocyclops, 5 species of Mesocyclops and 2 species of Thermocyclops from Cyclopidae were identified in 15 populations. Moreover, we detected 18 unique haplotypes, which fell into two distinct clades. Pairwise genetic distances (uncorrected p-distances) among the species of Cyclopidae ranged from 0.05 to 0.257. Several species co-existed in the same lake, and some haplotypes were shared among different geographic populations, suggesting a dispersal of Cyclopidae in our sampling region. Finally, we found that the population genetic diversity for each species of Cyclopidae was low in Nigeria. CONCLUSIONS: Our findings explored the species diversity and distribution of copepods within the family Cyclopidae for 15 Nigerian freshwater ecosystems: a high species diversity of Cyclopidae copepods was detected over a small geographic sampling range. Results from this study contribute to a better understanding of copepod diversity of Nigerian freshwater ecosystems.


title: Monitoring Leishmania infection and exposure to Phlebotomus perniciosus using minimal and non-invasive canine samples

text: BACKGROUND: In endemic areas of zoonotic leishmaniosis caused by L. infantum, early detection of Leishmania infection in dogs is essential to control the dissemination of the parasite to humans. The aim of this study was to evaluate the serological and/or molecular diagnostic performance of minimally and non-invasive samples (conjunctiva cells (CS) and peripheral blood (PB)) for monitoring Leishmania infection/exposure to Phlebotomus perniciosus salivary antigens in dogs at the beginning and the end of sand fly seasonal activity (May and October, respectively) and to assess associated risks factors. METHODS: A total of 208 sheltered dogs from endemic areas of leishmaniosis were screened. Leishmania DNA detection in PB on filter paper and CS was performed by nested-PCR (nPCR), while the detection of anti-Leishmania antibodies was performed using IFAT and ELISA. The exposure to P. perniciosus salivary antigens (SGH, rSP01 and rSP03B + rSP01) was measured by ELISA. RESULTS: Ninety-seven (46.6%) and 116 (55.8%) of the 208 dogs were positive to Leishmania antibodies or DNA by at least one test at the beginning and end of the sand fly season, respectively. IFAT and ELISA presented a substantial agreement in the serodiagnosis of leishmaniosis. Discrepant PB nPCR results were obtained between sampling points. Leishmania DNA was detected in CS of 72 dogs at the end of the phlebotomine season. The presence of antibodies to the parasite measured by ELISA was significantly higher in dogs presenting clinical signs compatible with leishmaniosis at both sampling points. Phlebotomus perniciosus salivary antibodies were detected in 179 (86.1%) and 198 (95.2%) of the screened dogs at the beginning and end of the phlebotomine season, respectively. CONCLUSIONS: The association between ELISA positivity and clinical signs suggests its usefulness to confirm a clinical suspicion. CS nPCR seems to be an effective and non-invasive method for assessing early exposure to the parasite. PB nPCR should not be used as the sole diagnostic tool to monitor Leishmania infection. The correlation between the levels of antibodies to P. perniciosus saliva and Leishmania antibodies suggests the use of a humoral response to sand fly salivary antigens as biomarkers of L. infantum infection. [Image: see text]


The role of molecular diagnosis in acute respiratory tract infection


Clustering of Feline Coronaviruses in Multicat Households


Simultaneous detection and typing of human metapneumovirus strains in nasopharyngeal secretions and cell cultures by monoclonal antibodies


Seasonal respiratory virus testing in management of adult cystic fibrosis patients


Absence of Melaka-virus in European children with respiratory disease


Respiratory Viral and Atypical Pneumonias


Comments on “Impact of bronchoalveolar lavage multiplex polymerase chain reaction on microbiological yield and therapeutic decisions in severe pneumonia in intensive care unit”


A highly efficient in vivo plasmid editing tool based on CRISPR-Cas12a and phage λ Red recombineering


Respiratory viruses and acute asthma in children


Broad reactivity of the Luminex xTAG Respiratory Virus Panel (RVP) assay for the detection of human rhinoviruses


title: IV, 6. Calicivirus RNA recombination

text: RNA recombination apparently contributed to the evolution of CVs. Nucleic acid sequence homology or identity and similar RNA secondary structure of CVs and non-CVs may provide a locus for recombination within CVs or with non-CVs should co-infections of the same cell occur. Natural recombinants have been demonstrated among other enteric viruses, including Picornaviridae (Kirkegaard and Baltimore, 1986; Furione et al., 1993), Astroviridae (Walter et al., 2001), and possibly rotaviruses (e.g., Desselberger, 1996; Suzuki et al., 1998), augmenting the natural diversity of these pathogens and complicating viral gastroenteritis prevention strategies based upon traditional vaccines. Such is the case for CVs and Astroviridae, whose recombinant strains may be a common portion of naturally circulating strains. The taxonomic — and perhaps biologic — limits of recombination are defined by the suggested recombination of Nanovirus and CV, viruses from hosts of different biologic orders; the relationship of picornaviruses and CVs, viruses in different families, as recombination partners; and the intra-generic recombination between different clades of NLVs.


title: Atypical respiratory pathogens

text: The main atypical pathogens in respiratory tract infections are classified on the basis of their ability to cause atypical pneumonia. This is not a well-defined clinical entity, and it is evident that atypical pathogens can sometimes cause ‘typical’ pneumonias and vice versa. This emphasizes the need for microbiological diagnosis, since it affects the selection of proper treatment, in which β-lactam antibiotics and aminoglycosides are not effective. Moreover, mixed infections caused by atypical and typical pathogens together are common. At this moment rapid and sensitive diagnostic methods are lacking. Besides numerous viruses, the main bacterial pathogens causing atypical pneumonias are Mycoplasma pneumoniae, two chlamydial species, Chlamydia pneumoniae and C. psittaci, one rickettsia, Coxiella burnetti, and several Legionella species. The majority of these pathogens cause upper respiratory tract infections more often than overt pneumonias. An atypical agent, Chlamydia pneumoniae, has also been associated with chronic inflammatory conditions in the cardiovascular system. The most recently discovered pathogen in atypical pneumonias is a hantavirus causing hantavirus pulmonary syndrome.


title: First report of two consecutive respiratory syncytial virus outbreaks by the novel genotypes ON-1 and NA-2 in a neonatal intensive care unit()

text: OBJECTIVE: Respiratory syncytial virus is a pathogen frequently involved in nosocomial outbreaks. Although several studies have reported nosocomial outbreaks in neonatal intensive care units, molecular epidemiology data are scarce. Here, the authors describe two consecutive respiratory syncytial virus outbreaks caused by genotypes ON-1 and NA-2 in a neonatal intensive care unit in São Paulo, Brazil. METHODS: A prospective search for respiratory syncytial virus was performed after diagnosing the index case and four other symptomatic newborns in the neonatal intensive care unit. Nasopharyngeal aspirate samples of all patients in the neonatal intensive care unit were tested for 17 respiratory viruses using real-time reverse transcriptase polymerase chain reaction. Genotyping was performed using nucleotide sequencing. RESULTS: From May to August 2013, two different outbreaks were detected in the neonatal intensive care unit. A total of 20 infants were infected with respiratory syncytial virus-A (ten and 14 with ON-1 and NA-2 genotypes, respectively). The mean age of the infants was 10 days, mean birth weight was 1,961 g, and the mean gestational age was 33 weeks. Risk factors (heart disease, lung disease, and prematurity) were present in 80% and 85.7% of infants in the ON-1 and NA-2 groups, respectively. In total, 45.8% of infants were asymptomatic and 20.8% required mechanical ventilation. Coinfections were not detected during the outbreaks. CONCLUSIONS: Infants in a neonatal intensive care unit who develop abrupt respiratory symptoms should be tested for respiratory viruses, especially respiratory syncytial virus. Even in the absence of severe symptoms, respiratory syncytial virus detection can prevent nosocomial transmission through infection control measures. A better understanding of respiratory syncytial virus molecular epidemiology is essential for developing new vaccines and antiviral drugs against respiratory syncytial virus.


Bronchiectasis: working together for better evidence


Feline infectious diseases: Our curiosity could be their salvation


title: Food-borne and water-borne diseases under climate change in low- and middle-income countries: Further efforts needed for reducing environmental health exposure risks

text: This paper provides a view of the major facts and figures related to infectious diseases with a focus on food-borne and water-borne diseases and their link with environmental factors and climate change. The global burden of food-borne diseases for 31 selected hazards was estimated by the World Health Organization at 33 million disability-adjusted life years (DALYs) in 2010 with 40% of this burden concentrated among children under 5 years of age. The highest burden per population of food-borne diseases is found in Africa, followed by Southeast Asia and the Eastern Mediterranean sub-regions. Unsafe water used for the cleaning and processing of food is a key risk factors contributing to food-borne diseases. The role of quality and quantity of water to the general burden of infectious diseases deserves attention, particularly in low- and middle-income countries, as its effects go beyond the food chain. Water-related infectious diseases are a major cause of mortality and morbidity worldwide, and climate change effects will exacerbate the challenges for the public health sector for both food-borne and water-borne diseases. Selected case studies from Africa and Asia show that (i) climate change extreme events, such as floods, may exacerbate the risks for infectious diseases spreading through water systems, and (ii) improvements related to drinking water, sanitation and hygiene could result in a significant reduction of intestinal parasitic infections among school-aged children. There is a need to better anticipate the impacts of climate change on infectious diseases and fostering multi-stakeholder engagement and multi-sectoral collaborations for integrated interventions at schools, community and household levels. The paper calls for giving priority to improving the environmental conditions affecting food-borne and water-borne infectious diseases under climate change.


Viral pharyngitis


Classical and molecular techniques for the diagnosis of viral gastroenteritis()


Ribavirin


title: Randomised, controlled trial of effectiveness of ampicillin in mild acute respiratory infections in Indonesian children

text: The recommended treatment for mild acute respiratory infections (ARI) in children is supportive care only, but many physicians, especially in developing countries, continue to prescribe antibiotic treatment because they believe it prevents progression to more severe ARI. To find out whether ampicillin treatment conferred any benefit over supportive care alone, a randomised, controlled trial was carried out among 889 children (under 5 years) with mild ARI in Indonesia. 447 were randomly allocated ampicillin (25-30 mg/kg body weight three times daily for 5 days) plus supportive care (continued breastfeeding, clearing of the nose, and paracetamol to control fever); 442 were allocated supportive care only. The treatment groups were almost identical after randomisation in terms of age, sex, level of parental education, history of measles immunisation, and fever. After 1 week the percentages cured were nearly identical (204 [46%] ampicillin; 209 [47%] control), as were the percentages of cases progressing to moderate ARI (56 [13%] vs 53 [12%]). The effect of treatment was not modified by age, sex, measles immunisation status, or the educational level of the parents. At the 2-week follow-up, the percentages cured were 62% (277) in the ampicillin group and 58% (256) in the control group; 14% of both groups had progressed to moderate ARI; and 24% (107) and 28% (123), respectively, still had mild ARI. None of the differences in outcome between the ampicillin and control groups was statistically significant. Thus, ampicillin plus supportive care offers no benefit over supportive care alone for treatment of mild ARI in young Indonesian children.


title: The wheezing infant

text: Wheeze is a symptom and not a diagnosis. It is extremely common in infancy; 20-30% of children have experienced recurrent episodic wheezing by the age of 12 months. Wheezing may result from widespread peripheral airway narrowing or, less commonly, from localized central disease. Excluding recurrent viral wheezing and asthma-like symptoms, all other specific causes of wheezing (e.g. cystic fibrosis, congenital airway disorders, chronic lung disease of prematurity) affect only 2-3% of the population. Although wheezing disease preceded by acute viral bronchiolitis early in infancy features prominently in most articles on childhood asthma, it affects, at most, 1% of the population. The increased prevalence of reported wheezing in industrialized countries until the mid-1990s, accompanied by an increase in the number of hospital admissions for wheezing, represents a true increase in the problem rather than simply increased awareness. In the UK, wheezing in pre-school children accounts for about 25% of acute hospital admissions in childhood, and almost 50% during epidemics of respiratory syncytial virus (RSV) infection.


Virus-virus and virus-bacterium associations in the etiology of tuberculous and nontuberculous pneumopatia, during influenza season


Impact of a poorly performing point-of-care test during the 2017-2018 influenza season


title: T cell sensitization to proteolipid protein in myelin basic protein-induced relapsing experimental allergic encephalomyelitis

text: (SJL/J × PL/J)F(1) mice immunized with myelin basic protein (MBP) develop an autoimmune demyelinating disease termed relapsing experimental allergic encephalomyelitis (rEAE). The acute stage of disease is mediated by CD4(+) T cells specific for MBP amino acids 1–9. To determine the immunologic bases for disease relapse, host sensitization to additional autoantigens of the central nervous system was measured. Results indicate that most animals develop T cell reactivity to endogenous myelin proteolipid protein (PLP) during rEAE. However, PLP-specific immunity does not appear to accound for expression of relapse episodes of demyelination. relapse episodes of demyelination.


GASTROINTESTINAL AND NUTRITIONAL PROBLEMS IN CHILDREN WITH IMMUNODEFICIENCY AND AIDS


SCANDINAVIAN EPIDEMIC NEPHROPATHY AND KOREAN HÆMORRHAGIC FEVER


Infectious wastes: Myths and realities


Virus evolution


The epidemiology of respiratory infections in children()


title: Viral cytopathogenicity correlated with integration of ubiquitin-coding sequences()

text: The RNA genomes of cytopathogenic bovine viral diarrhea virus (BVDV) isolates contain insertions highly homologous to cellular sequences. For two of them the insert was identified as ubiquitin coding sequence. The genome of BVDV Osloss contains exactly one ubiquitin gene monomer. In the case of BVDV CP1 the cellular insertion comprises one complete ubiquitin gene and part of a second monomer. The host cell-derived element in the CP1 genome is embedded in a large duplication of about 2.4 kb of viral sequences. Cellular insertion and duplication were not found in the genome of NCP1, the noncytopathogenic counterpart of CP1. These results strongly suggest that recombination between viral and cellular RNA is responsible for development of the cytopathogenic viruses, which is linked to pathogenesis of a lethal disease in cattle.


VIRUS-LIKE PARTICLES IN INFECTIOUS HEPATITIS


title: Cold calling

text: Vaccination against flu viruses is well established and reasonably successful…


title: Contrasting effects of immunosuppression on herpes simplex virus type I (HSV I) induced central nervous system (CNS) demyelination in mice

text: We previously reported that lip inoculation of Herpes simplex virus type I (HSV I) in specific strains of mice would induce multifocal brain demyelination (MBD). The mechanisms mediating the development of MBD are unknown. In this study, five inbred strains of mice (C57BL/6J, Balb/cByJ, A/J, SJL/J, PL/J) immunosuppressed with either irradiation (IR), cyclophosphamide (CY), or cyclosporin A (CP) along with three immune deficient strains (C57BL/6J nu/nu, Balb/cByJ nu/nu, C57BL/6J bg/bg) were lip inoculated with HSV I to determine the effect of immunosuppression on viral spread throughout the brain and the development of demyelination during the acute stage of infection. Mortality increased in all groups when compared with controls but was greatest in A/J, SJL/J, and PL/J strains, where all mice died before day 6 PI. In contrast with immunocompetent C57BL/6J mice where virus is restricted to the brainstem, virus spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, and C57BL/6J bg/bg mice. Despite viral spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, Balb/cByJ and Balb/cByJ nu/nu mice, MBD did not develop. MBD did develop however, in both HSV I infected C57BL/6J bg/bg and CP treated Balb/cByJ mice. Immunosuppression of HSV I infected Balb/cByJ mice prevents the development of demyelination at the trigeminal root entry zone (TREZ) of the brainstem while in Balb/cByJ nu/nu mice, the extent of demyelination at TREZ was reduced and delayed when compared with immunocompetent controls. These results suggest that the immune system plays an important role in limiting viral spread in the brain as well as in the development of demyelination at TREZ and of MBD throughout the brain during the acute phase of infection. Virus alone does not induce MBD in this animal model of virus induced CNS demyelination but is a prerequisite for its development.


title: How ‘hidden’ reading frames are expressed

text: Secondary reading frames, ‘hidden’ under other reading frames, are used for coordinated expression of proteins in several eukaryotic viruses. In some genes, ribosomal frameshifting and initiation or reinitiation of protein synthesis on internal AUG codons are translational mechanisms allowing access to such ‘hidden’ reading frames. In others, secondary reading frames are translated from alternatively spliced or edited mRNAs.


title: Expression patterns of the ectopeptidases aminopeptidase N/CD13 and dipeptidyl peptidase IVICD26: immunoultrastructural topographic localization on different types of cultured cells

text: Aminopeptidase N/CD13 and dipeptidyl peptidase IV/CD26 are widespread membrane-bound peptidases involved in fundamental biological processes. Using cryo-ultramicrotomy of cultured cells followed by indirect immunogold labelling, both enzymes appeared to be strongly and regularly labelled on the cell surfaces of human synovial fibroblasts, T-Iymphocytes and colon carcinoma cells Caco-2. In the cytoplasm of the synovial fibroblasts gold-labelled vesicle-like structures were found, which we consider to be potential transport vesicles. An abundant and regular expression of CD13 was detected on cultured renal parenchymal cells. On the renal carcinoma cell line Caki-l cells we found a low, non-homogeneous and clustered CD13-labelling. On cultured renal parenchymal cells and the Caki-l cells CD26 could not be observed. The expression pattern of CD26 on renal carcinoma cell line Caki-2 cells showed also a slightly clustered distribution. A low density CD26-labelling was present on the squamous cell carcinoma cell line UM-SCC-22B. CD13 was absent in Caki-2 and UMSCC-22B cells. The presence of both enzymes on the cultured cells enables their ultrastructural investigation under different growth conditions and their involvement in cell-cell interactions. For this purpose, however, further investigations are necessary.


title: Avsunviroidae family: Viroids containing hammerhead ribozymes

text: This chapter focuses on the second viroid family, whose members are also referred to as hammerhead viroids, taking into account their most outstanding feature. If the word “small” is the first to come to mind when considering viroids, perhaps the second word is “hammerhead,” because this class of ribozymes, which because of its structural simplicity has an enormous biotechnological potential, is described in avocado sunblotch viroid (ASBVd) as well as in a viroid-like satellite RNA. The most outstanding feature of the Avsunviroidae members is their potential to adopt hammerhead structures in both polarity strands and to self-cleave in vitro accordingly. Viroids differ from viruses not only in their genome size but also in other fundamental aspects, prominent among which is the lack of messenger activity of both viroid RNAs and their complementary strands.


title: Mouse neuropathogenic poliovirus strains cause damage in the central nervous system distinct from poliomyelitis

text: Poliomyelitis as a consequence of poliovirus infection is observed only in primates. Despitea host range restricted to primates, experimental infection of rodents with certain genetically well defined poliovirus strains produces neurological disease. The outcome of infection of mice with mouse-adapted poliovirus strains has been described previously mainly in terms of paralysis and death, and it was generally assumed that these strains produce the same disease syndromes in normal mice and in mice transgenic for the human poliovirus receptor (hPVR-tg mice). We report a comparison of the clinical course and the histopathological features of neurological disease resulting from intracerebral virus inoculation in normal micewith those of murine poliomyelitis in hPVR-tg mice. The consistent pattern of clinical deficits in poliomyelitic transgenic mice contrasted with highly variable neurologic disease that developed in mice infected with different mouse-adapted polioviruses. Histopathological analysis showed a diffuse encephalomyelitis induced by specific poliovirus serotype 2 isolates in normal mice, that affected neuronal cell populations without discrimination, whereas in hPVR-tg animals, damage was restricted to spinal motor neurons. Mouse neurovirulent strains of poliovirus type 2 differed from mouse neurovirulent poliovirus type 1 derivatives in their ability to induce CNS lesions. Our findings indicate that the characteristic clinical appearance and highly specific histopathological features of poliomyelitis are mediated by the hPVR. Our data lead us to conclude that the tissue tropism of mouse-adapted poliovirus strains in normal mice is fundamentally different from that of poliovirus in hPVR-tg mice and primates, and that this is indicative of an as yet unknown mechanism of adsorption and uptake of the virus into cells of the murine CNS.


title: Alphaviruses — vectors for the expression of heterologous genes

text: DNA viruses and retroviruses are well established as vectors for the expression of heterologous genes, but there is increasing interest in the possibilities of using RNA viruses, which do not replicate through a DNA intermediate, for this purpose. This article summarizes some of the general properties of RNA viruses and concentrates on one class of RNA viruses — the alphaviruses — and their potential as expression vectors.