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Treatment of idiopathic spasmodic torticollis with botulinum‐A toxin: a pilot study of 19 patients

Nineteen patients with spasmodic torticollis, unresponsive to standard therapy, were administered local injections of botulinum‐A toxin into the affected muscles. During an average follow‐up period of 11.5 months, a more than 25% improvement was noted in 14 of 19 patients. All those with purely focal dystonia and 9 of 10 patients with a disease history of less than three years benefited from treatment. Side effects were insignificant and transient. Botulinum toxin is a very effective and safe method of treatment for spasmodic torticollis.

A high frequency of allopolyploid speciation in the gymnospermous genus Ephedra and its possible association with some biological and ecological features

The origin and evolution of polyploids have been studied extensively in angiosperms and ferns but very rarely in gymnosperms. With the exception of three species of conifers, all natural polyploid species of gymnosperms belong to Ephedra, in which more than half of the species show polyploid cytotypes. Here, we investigated the origin and evolution of polyploids of Ephedra distributed in the Qinghai–Tibetan Plateau (QTP) and neighbouring areas. Flow cytometry (FCM) was used to measure the ploidy levels of the sampled species that are represented by multiple individuals from different populations, and then, two single‐copy nuclear genes (LFY and DDB2) and two chloroplast DNA fragments were used to unravel the possible origins and maternal donors of the polyploids. The results indicate that the studied polyploid species are allopolyploids, and suggest that allotetraploidy is a dominant mode of speciation in Ephedra. The high percentage of polyploids in the genus could be related to some of its biological attributes such as vegetative propagation, a relatively high rate of unreduced gamete formation, and a small genome size relative to most other gymnosperms. Significant ecological divergences between allotetraploids and their putative progenitors were detected by PCAs and anova and Tukey's tests, with the exception of E. saxatilis. The overlap of geographical distributions and ecological niches of some diploid species could have provided opportunities for interspecific hybridization and allopolyploid speciation.

Distribution of split DnaE inteins in cyanobacteria

Inteins are genetic elements found inside the coding regions of different host proteins and are translated in frame with them. The intein‐encoded protein region is removed by an autocatalytic protein‐splicing reaction that ligates the host protein flanks with a peptide bond. This reaction can also occur in trans with the intein and host protein split in two. After translation of the two genes, the two intein parts ligate their flanking protein parts to each other, producing the mature protein. Naturally split inteins are only known in the DNA polymerase III alpha subunit (polC or dnaE gene) of a few cyanobacteria. Analysing the phylogenetic distribution and probable genetic propagation mode of these split inteins, we conclude that they are genetically fixed in several large cyanobacterial lineages. To test our hypothesis, we sequenced parts of the dnaE genes from five diverse cyanobacteria and found all species to have the same type of split intein. Our results suggest the occurrence of a genetic rearrangement in the ancestor of a large division of cyanobacteria. This event fixed the dnaE gene in a unique two‐genes one‐protein configuration in the progenitor of many cyanobacteria. Our hypothesis, findings and the cloning procedure that we established allow the identification and acquisition of many naturally split inteins. Having a large and diverse repertoire of these unique inteins will enable studies of their distinct activity and enhance their use in biotechnology.

Could preventive intranasal interferon lower the morbidity in children prone to respiratory illness?

Recent studies have demonstrated that rhinovirus infections can be prevented in the family setting through use of intranasal interferon sprays which are commenced when another family member develops a cold. One hundred and twenty‐seven children aged 4–9 years who had been hospitalized during their first year of life for severe infections caused by respiratory syncytial virus were studied virologically and epidemiologically during a seven‐month period which included the winter months. The hypothesis was that a significant part of their respiratory morbidity would be preventable by a contact prophylaxis approach using intranasal interferon. However, the findings suggest that a preventive approach of this kind would not substantially reduce the burden of respiratory illness in these children because: the target children themselves more often introduced illness into the family than did other household members; rhinovirus infections preventable by interferon were associated with little lower respiratory morbidity; and rhinoviruses were minor contributors to the total respiratory illness burden in these respiratory illness‐prone children.

Use of Protein A in the Serum‐in‐Agar Diffusion Method in Immune Electron Microscopy for Detection of Virus Particles in Cell Culture

A modified technique using protein A in the serum‐in‐agar (SIA) method for immune electron microscopy (IEM) was presented. Grids coated with staphylococcal protein A were floated on samples mounted on agar containing 2% antiserum and incubated at 37 C, for 60 min. After washing and staining, the grids were observed in an electron microscope. The effects of protein A on virus detection were evaluated using poliovirus and bovine rotavirus infected cell culture fluids. The results showed that the technique using protein A (PA‐SIA) had at least 10‐fold higher sensitivity for virus detection than the original SIA. The optimal concentration of protein A was 1 to 10 μg/ml for coating the grids to trap virus particles. The PA‐SIA method was also compared with immunosorbent electron microscopy (ISEM). The former showed higher or at least the same sensitivity and some advantages in detecting antigen‐antibody reaction than the latter method. These results indicate that our PA‐SIA method may be superior to other IEM techniques presented previously for the detection and identification of viruses.

The integral membrane protein from a virulent isolate of transmissible gastroenteritis virus: molecular characterization, sequence and expression in Escherichia coli

Subgenomic mRNA from a virulent isolate of porcine transmissible gastroenteritis virus (TGEV) was used to produce cDNA clones. Part of a new clone and a previously reported clone were sequenced and used to construct the viral gene for integral membrane protein. A single open reading frame (ORF) encoding a polypeptide of 262 amino acids, relative molecular mass (M(r)) 29459, was identified. The positive identification of the polypeptide as the integral membrane protein was demonstrated by the production in E. coli of a chimaeric protein comprising most of the ORF encoding the M(r) 29459 polypeptide and β‐galactosidase. The chimaeric protein reacted with a specific monoclonal antibody to viral integral membrane protein and antibodies raised against the chimaeric protein immune precipitated the viral protein. Comparison with the sequence of an avirulent isolate indicates amino acid residues that may be important in pathogenicity.

Looking Forward to Serving SID

Differential Expression of the Major Histocompatibility Antigen Complex (MHC) on a Series of Burkitt's Lymphoma Lines

We compared the expressions of class I and class II major histocompatibility antigen complex (MHC) on the surface of Jijoye and P3HR‐1 cells of Burkitt's lymphoma sublines. Jijoye cells had a large amount of class I and class II MHC antigens, whereas these antigens were less expressed on P3HR‐1 cells. On a subline of P3HR‐1 K cells the expression of class I antigen markedly diminished and class II antigen was undetectable. On the other hand, Jijoye, P3HR‐1, and P3HR‐1 K cell lines were confirmed to be Epstein‐Barr virus (EBV) nonproducer, low producer, and high producer, respectively. The chemical activation of EBV genome by treating P3HR‐1 cells with 12‐O‐tetradecanyl phorbol‐13 acetate (TPA) and n‐butyrate resulted in inhibition of the expression of class I and II antigens, while the addition of retinoic acid, an inhibitor of virus replication, blocked the decrease in the MHC antigen expression. These findings suggested that there might be an inverse correlation between the virus production and the expression of class I and II MHC antigens.

Australia was indeed the “lucky country” in the recent worldwide SARS epidemic

Sequence of the nucleoprotein gene from a virulent British field isolate of transmissible gastroenteritis virus and its expression in Saccharomyces cerevisiae

Subgenomic mRNA from a virulent isolate of porcine transmissible gastroenteritis virus (TGEV) was used to produce cDNA which was sequenced. Two non‐overlapping open reading frames (ORFs) were identified. The largest, encoding a polypeptide of 382 amino acids (relative molecular mass (M(r)) 43 483), was shown to be the viral nucleoprotein gene. The second ORF, found 3’to the larger ORF, encodes a polypeptide of 78 amino acids (M(r) 9068) which has yet to be assigned to a viral product. The nucleoprotein gene was expressed in yeast cells under the control of two types of yeast promoters: the constitutive PGK promoter, and the inducible GAL1 promoter. Yeast cells containing recombinant plasmids, with the nucleoprotein gene in the correct orientation, produced a polypeptide of M, 47000, identical to the viral product, that reacted with a specific monoclonal antibody.

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2003–2004

This review is the third update of the original review, published in 1999, on the application of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings the topic to the end of 2004. Both fundamental studies and applications are covered. The main topics include methodological developments, matrices, fragmentation of carbohydrates and applications to large polymeric carbohydrates from plants, glycans from glycoproteins and those from various glycolipids. Other topics include the use of MALDI MS to study enzymes related to carbohydrate biosynthesis and degradation, its use in industrial processes, particularly biopharmaceuticals and its use to monitor products of chemical synthesis where glycodendrimers and carbohydrate–protein complexes are highlighted. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:273–361, 2009

The dual role of thymidine phosphorylase in cancer development and chemotherapy

Thymidine phosphorylase (TP), also known as “platelet‐derived endothelial cell growth factor” (PD‐ECGF), is an enzyme, which is upregulated in a wide variety of solid tumors including breast and colorectal cancers. TP promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. Elevated levels of TP are associated with tumor aggressiveness and poor prognosis. Therefore, TP inhibitors are synthesized in an attempt to prevent tumor angiogenesis and metastasis. TP is also indispensable for the activation of the extensively used 5‐fluorouracil prodrug capecitabine, which is clinically used for the treatment of colon and breast cancer. Clinical trials that combine capecitabine with TP‐inducing therapies (such as taxanes or radiotherapy) suggest that increasing TP expression is an adequate strategy to enhance the antitumoral efficacy of capecitabine. Thus, TP plays a dual role in cancer development and therapy: on the one hand, TP inhibitors can abrogate the tumorigenic and metastatic properties of TP; on the other, TP activity is necessary for the activation of several chemotherapeutic drugs. This duality illustrates the complexity of the role of TP in tumor progression and in the clinical response to fluoropyrimidine‐based chemotherapy. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 6, 903–953, 2009

Hydrocephalus in Suckling Rats Infected Intracerebrally with Mouse Hepatitis Virus, MHV‐A59

After intracerebral inoculation of mouse hepatitis virus, MHV‐A59 strain, into 3‐ to 5‐day‐old Wistar rats, some survivors at 14 days postinoculation (p.i.) were found to lack the cerebral cortex and to have an accumulation of a considerable amount of cerebrospinal fluid. The virus titer in the brain increased exponentially after inoculation, reaching a maximum 4 to 6 days p.i. when immunofluorescence revealed virus‐specific antigen within neurons in the cerebral cortex. A small amount of infectious virus was also detectable 14 days p.i. when the cerebral anomaly was evident. This brain malformation causing hydrocephalus was due to cerebral damage by viral infection.

Ancestral acquisitions, gene flow and multiple evolutionary trajectories of the type three secretion system and effectors in Xanthomonas plant pathogens

Deciphering the evolutionary history and transmission patterns of virulence determinants is necessary to understand the emergence of novel pathogens. The main virulence determinant of most pathogenic proteobacteria is the type three secretion system (T3SS). The Xanthomonas genus includes bacteria responsible for numerous epidemics in agroecosystems worldwide and represents a major threat to plant health. The main virulence factor of Xanthomonas is the Hrp2 family T3SS; however, this system is not conserved in all strains and it has not been previously determined whether the distribution of T3SS in this bacterial genus has resulted from losses or independent acquisitions. Based on comparative genomics of 82 genome sequences representing the diversity of the genus, we have inferred three ancestral acquisitions of the Hrp2 cluster during Xanthomonas evolution followed by subsequent losses in some commensal strains and re‐acquisition in some species. While mutation was the main force driving polymorphism at the gene level, interspecies homologous recombination of large fragments expanding through several genes shaped Hrp2 cluster polymorphism. Horizontal gene transfer of the entire Hrp2 cluster also occurred. A reduced core effectome composed of xopF1, xopM, avrBs2 and xopR was identified that may allow commensal strains overcoming plant basal immunity. In contrast, stepwise accumulation of numerous type 3 effector genes was shown in successful pathogens responsible for epidemics. Our data suggest that capacity to intimately interact with plants through T3SS would be an ancestral trait of xanthomonads. Since its acquisition, T3SS has experienced a highly dynamic evolutionary history characterized by intense gene flux between species that may reflect its role in host adaptation.

Preventing local transmission of SARS: lessons from Singapore

SARS and its effect on medical education in Hong Kong

The receptor for Bacillus thuringiensis CrylA(c) delta‐endotoxin in the brush border membrane of the lepidopteran Manduca sexta is aminopeptidase N

A 120 kDa glycoprotein in the larval midgut membrane of the Iepidopteran Manduca sexta, previously identified as a putative receptor for Bacillus thuringiensis CrylA(c) δ‐endotoxin, has been purified by a combination of protoxin affinity Chromatography and anion exchange chromatography. In immunoblotting experiments, the purified glycoprotein has the characteristics predicted of the receptor: it binds CrylA(c) toxin In the presence of GlcNAc but not GalNAc; it binds the lectin SBA; but it does not bind CrylB toxin. N‐terminal and internal amino acid sequences obtained from the protein show a high degree of similarity with the enzyme aminopeptidase N (EC 3.4.11.2). When assayed for aminopeptidase activity, purified receptor preparations were enriched 5.3‐fold compared to M. sexta brush border membrane vesicles. We propose that the receptor for CrylA(c) toxin in the brush border membrane of the lepidopteran M. sexta is the metalloprotease aminopeptidase N.

Molecular characteristics and pathogenic assessment of porcine epidemic diarrhoea virus isolates from the 2018 endemic outbreaks on Jeju Island, South Korea

Since the 2013–2014 incursion of the virulent G2b porcine epidemic diarrhoea virus (PEDV) pandemic strains in South Korea, frequent moderate‐scale regional outbreaks have recurred. In particular, areas of Jeju Island with extensive swine production have faced repeated epidemics since the re‐emergence in 2014. The current study reports the complete genome sequences and molecular characterization of the representative PEDV strains responsible for the 2018 endemic outbreaks on Jeju Island. All isolates were determined to belong genetically to the highly pathogenic pandemic G2b group. Full‐length genome sizes of four isolates differed from that of the G2b epidemic field strain due to insertion or deletion (DEL) mutations in the non‐structural protein (nsp)‐ or spike (S) protein‐coding regions. The 2018 Jeju isolates shared 96.7%–98.7% and 98.5%–99.4% identity at the S gene and whole‐genome levels, respectively, compared to global G2b PEDV strains. Genetic and phylogenetic analyses indicated that the 2018 isolates were closest to the 2014 G2b re‐emergent Jeju strains, but appeared to have undergone substantial rapid independent evolution. Among the isolates, a notable nsp3 DEL variant strain, KOR/KNU‐1807/2018, was isolated and propagated by continuous passages in Vero cells, and displayed typical PEDV‐induced syncytia formation. Genomic sequencing identified a unique 8‐nt DEL in the extreme C‐terminal region of the S gene at the 4th passage (KNU‐1807‐P4) compared to its original sample. This DEL resulted in the premature termination of S by nine amino acid residues (EVFEKVHVQ), which contained a KxHxx motif that is a potential endoplasmic reticulum retrieval signal. In vivo animal studies showed that variant strain KNU‐1807 had decreased virulence in suckling piglets. These results advance our knowledge regarding the genetic variation and pathogenicity of the G2b PEDV endemic strains prevalent in Jeju swine herds in South Korea.

Emergence and adaptive evolution of Nipah virus

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

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

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].

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

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.

Non‐human viruses developed as therapeutic agent for use in humans

Viruses usually infect a restricted set of host species, and only in rare cases does productive infection occur outside the natural host range. Infection of a new host species can manifest as a distinct disease. In this respect, the use of non‐human viruses in clinical therapy may be a cause for concern. It could provide the opportunity for the viruses to adapt to the new host and be transferred to the recipient's relatives or medical caretakers, or even to the normal host species. Such environmental impact is evidently undesirable. To forecast future clinical use of non‐human viruses, a literature study was performed to identify the viruses that are being considered for application as therapeutic agents for use in humans. Twenty‐seven non‐human virus species were identified that are in (pre)clinical development, mainly as oncolytic agents. For risk management, it is essential that the potential environmental consequences are assessed before initiating clinical use, even if the virus is not formally classified as a genetically modified organism. To aid such assessment, each of these viruses was classified in one of five relative environmental risk categories, ranging from “Negligible” to “Very High”. Canary pox virus and the Autographa californica baculovirus were assigned a “Negligible” classification, and Seneca Valley virus, murine leukemia virus, and Maraba virus to the “High” category. A complicating factor in the classification is the scarcity of publicly available information on key aspects of virus biology in some species. In such cases the relative environmental risk score was increased as a precaution. Copyright © 2011 John Wiley & Sons, Ltd.

From the Editors

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

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

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

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.

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

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

Viruses and autoimmunity: an affair but not a marriage contract

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.

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

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.

Saffold virus, an emerging human cardiovirus

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.

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

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

Borna disease virus

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.

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

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

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

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.

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

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.

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

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).

Serum Lipase Activity in Young Dogs With Acute Enteritis or Gastroenteritis

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

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

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.

Globalization and blood safety

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.

CONTRAST‐ENHANCED ULTRASONOGRAPHY OF THE SMALL BOWEL IN HEALTHY CATS

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

MAGNETIC RESONANCE IMAGING OF THE NORMAL AND DISEASED FELINE MIDDLE EAR

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

Unbuttoning normalcy – on cosmopolitical events

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

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

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.

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

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.

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

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

Phylogeny and classification of the Signiphoridae (Hymenoptera: Chalcidoidea)

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

A Nanostructured Microfluidic Immunoassay Platform for Highly Sensitive Infectious Pathogen Detection

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

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

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

Hepatitis E Virus and Related Viruses in Animals

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

Ribosomal frameshifting in yeast viruses

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.

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

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

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

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

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

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.

Current awareness on yeast

In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (4 weeks journals ‐ search completed 10th. Nov. 2004)

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

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

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

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.

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

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.

Design, Synthesis, and Evaluation of Bioactive Small Molecules

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

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

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

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

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