Mild to moderate influenza A(H7N9) infections detected through China’s national influenza-like Illness sentinel surveillance system

Poster Session: News and Views from the H7N9 OutbreakBackground: The “clinical iceberg” phenomenon, where there are usually many more infected cases than is apparent symptomatically and even less so registered in the clinical setting, is a common feature of influenza disease. While this is certainly true for interpandemic influenza and the 2009 influenza A(H1N1) pandemic, this appeared to be less substantial for the Dutch A(H7N7) outbreak, and with A(H5N1) being an acknowledged exception. It remains unknown whether the “iceberg” applies to the influenza A(H7N9) virus that emerged in early 2013 in China. While the majority of laboratory-confirmed A(H7N9) cases presented with a severe clinical picture to a hospital, a small number of laboratory-confirmed cases have been identified through the sentinel influenza-like illness (ILI) surveillance system nationwide. The objective of our study was to describe the clinical characteristics of the complete case series of A(H7N9) cases as of May 15, 2013, that were identified through routine testing by the ILI sentinel surveillance system. Materials and Methods: ILI sentinel surveillance in China is conducted through a network of 554 hospitals across the country, with the total number of outpatient and/or emergency department visits and the number of patients fitting the WHO standard ILI case definition reported weekly online to the China CDC, and 10-15 nasopharyngeal swabs collected from ILI patients each week for routine laboratory testing and subtyping. All A(H7N9) cases detected through the ILI surveillance system by May 15, 2013, were identified by cross-referencing the laboratory-confirmed A(H7N9) line list with the routine sentinel ILI surveillance system. Demographic and epidemiologic data were extracted from field investigation records, and clinical and laboratory data were obtained from medical chart review. Results: Five (3.8%) of a total of 130 laboratory-confirmed influenza A(H7N9) cases reported as of May 28, 2013, were detected through the routine ILI surveillance system. Four (80%) of them were male. Mean age was 13 (range = 2-26) years and none had any underlying medical condition. Exposure history, geographic location and timing of symptom onset were otherwise similar to the general cohort of all laboratory-confirmed cases to date. All patients experienced only mild or moderate disease with an uneventful course of recovery. Among them three (60%) were managed only as outpatients and all quickly recovered after 3-5 days, with nasopharyngeal swabs tested positive for A(H7N9) only after their full recovery. Two patients (40%) were hospitalized for treatment. One was a 4-year-old child from Shanghai who presented initially as an outpatient with fever and mild rhinorrhea to a routine sentinel clinic, and was admitted on the next day for oseltamivir treatment after his nasopharyngeal swab was tested positive for A(H7N9). The other was a 26-year-old man from Jiangsu who presented initially with fever and productive cough to a sentinel clinic, being given ceftazidime without improvement. He was admitted 4 days later with radiologic evidence of left-sided pneumonia, and started on oseltamivir and moxifloxacin. Both remained clinically stable with quick resolution of symptoms within 10 days. Conclusions: Our complete case series of A(H7N9) cases detected through the routine ILI surveillance system provide contrasting clinical presentations to the generally much more severe clinical picture of the majority of laboratory-confirmed A(H7N9) cases detected otherwise. Our findings provide indirect evidence of a substantial proportion of mild disease and support the existence of a “clinical iceberg” phenomenon in influenza A(H7N9) infections. For the clinician, our findings reinforce vigilance to the diverse presentation that can be associated with influenza A(H7N9) virus infections. Our results also suggest that large-scale community surveillance networks can be useful as a population-based sampling tool to enhance understanding of the full spectrum of disease, especially in the early phase of an evolving epidemic.published_or_final_versio

Detection of mild to moderate influenza A/H7N9 infection by China's national sentinel surveillance system for influenza-like illness: case series

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Fe3O4–Au and Fe2O3–Au Hybrid Nanorods: Layer-by-Layer Assembly Synthesis and Their Magnetic and Optical Properties

A layer-by-layer technique has been developed to synthesize FeOOH–Au hybrid nanorods that can be transformed into Fe2O3–Au and Fe3O4–Au hybrid nanorods via controllable annealing process. The homogenous deposition of Au nanoparticles onto the surface of FeOOH nanorods can be attributed to the strong electrostatic attraction between metal ions and polyelectrolyte-modified FeOOH nanorods. The annealing atmosphere controls the phase transformation from FeOOH–Au to Fe3O4–Au and α-Fe2O3–Au. Moreover, the magnetic and optical properties of as-synthesized Fe2O3–Au and Fe3O4–Au hybrid nanorods have been investigated

Transcriptome Sequencing and Characterization for the Sea Cucumber Apostichopus japonicus (Selenka, 1867)

Background: Sea cucumbers are a special group of marine invertebrates. They occupy a taxonomic position that is believed to be important for understanding the origin and evolution of deuterostomes. Some of them such as Apostichopus japonicus represent commercially important aquaculture species in Asian countries. Many efforts have been devoted to increasing the number of expressed sequence tags (ESTs) for A. japonicus, but a comprehensive characterization of its transcriptome remains lacking. Here, we performed the large-scale transcriptome profiling and characterization by pyrosequencing diverse cDNA libraries from A. japonicus. Results: In total, 1,061,078 reads were obtained by 454 sequencing of eight cDNA libraries representing different developmental stages and adult tissues in A. japonicus. These reads were assembled into 29,666 isotigs, which were further clustered into 21,071 isogroups. Nearly 40 % of the isogroups showed significant matches to known proteins based on sequence similarity. Gene ontology (GO) and KEGG pathway analyses recovered diverse biological functions and processes. Candidate genes that were potentially involved in aestivation were identified. Transcriptome comparison with the sea urchin Strongylocentrotus purpuratus revealed similar patterns of GO term representation. In addition, 4,882 putative orthologous genes were identified, of which 202 were not present in the non-echinoderm organisms. More than 700 simple sequence repeats (SSRs) and 54,000 single nucleotide polymorphisms (SNPs) were detected in the A. japonicu

ATP release during cell swelling activates a Ca2+-dependent Cl - Current by autocrine mechanism in mouse hippocampal microglia

Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl- channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1+/GFP mice by whole-cell patch-clamp and imaging techniques. The exposure of cells to a mild hypotonic medium, caused an outward rectifying current, developing in 5-10 minutes and reverting upon stimulus washout. This current, required for microglia ability to extend processes towards a damage signal, was carried mainly by Cl- ions and dependent on intracellular Ca2+. Moreover, it involved swelling-induced ATP release. We identified a purine-dependent mechanism, likely constituting an amplification pathway of current activation: under hypotonic conditions, ATP release triggered the Ca2+-dependent activation of anionic channels by autocrine purine receptors stimulation. Our study on native microglia describes for the first time the functional properties of stretch/swelling-activated currents, representing a key element in microglia ability to monitor the brain parenchyma

A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency

BackgroundOncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance.ResultsIn reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100x more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels.ConclusionThese new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.Peer reviewe

Genetic Networks of Liver Metabolism Revealed by Integration of Metabolic and Transcriptional Profiling

Although numerous quantitative trait loci (QTL) influencing disease-related phenotypes have been detected through gene mapping and positional cloning, identification of the individual gene(s) and molecular pathways leading to those phenotypes is often elusive. One way to improve understanding of genetic architecture is to classify phenotypes in greater depth by including transcriptional and metabolic profiling. In the current study, we have generated and analyzed mRNA expression and metabolic profiles in liver samples obtained in an F2 intercross between the diabetes-resistant C57BL/6 leptinob/ob and the diabetes-susceptible BTBR leptinob/ob mouse strains. This cross, which segregates for genotype and physiological traits, was previously used to identify several diabetes-related QTL. Our current investigation includes microarray analysis of over 40,000 probe sets, plus quantitative mass spectrometry-based measurements of sixty-seven intermediary metabolites in three different classes (amino acids, organic acids, and acyl-carnitines). We show that liver metabolites map to distinct genetic regions, thereby indicating that tissue metabolites are heritable. We also demonstrate that genomic analysis can be integrated with liver mRNA expression and metabolite profiling data to construct causal networks for control of specific metabolic processes in liver. As a proof of principle of the practical significance of this integrative approach, we illustrate the construction of a specific causal network that links gene expression and metabolic changes in the context of glutamate metabolism, and demonstrate its validity by showing that genes in the network respond to changes in glutamine and glutamate availability. Thus, the methods described here have the potential to reveal regulatory networks that contribute to chronic, complex, and highly prevalent diseases and conditions such as obesity and diabetes

Drugs and herbs given to prevent hepatotoxicity of tuberculosis therapy: systematic review of ingredients and evaluation studies

Background: Drugs to protect the liver are frequently prescribed in some countries as part of treatment for tuberculosis. The biological rationale is not clear, they are expensive and may do harm. We conducted a systematic review to a) describe the ingredients of "liver protection drugs"; and b) compare the evidence base for the policy against international standards. Methods: We searched international medical databases (MEDLINE, EMBASE, LILACS, CINAHL, Cochrane Central Register of Controlled Trials, and the specialised register of the Cochrane Infectious Diseases Group) and Chinese language databases (CNKI, VIP and WanFang) to April 2007. Our inclusion criteria were research papers that reported evaluating any liver protection drug or drugs for preventing liver damage in people taking anti-tuberculosis treatment. Two authors independently categorised and extracted data, and appraised the stated methods of evaluating their effectiveness. Results: Eighty five research articles met our inclusion criteria, carried out in China (77), India (2), Russia (4), Ukraine (2). These articles evaluated 30 distinct types of liver protection compounds categorised as herbal preparations, manufactured herbal products, combinations of vitamins and other non-herbal substances and manufactured pharmaceutical preparations. Critical appraisal of these articles showed that all were small, poorly conducted studies, measuring intermediate outcomes. Four trials that were described as randomised controlled trials were small, had short follow up, and did not meet international standards. Conclusion: There is no reliable evidence to support prescription of drugs or herbs to prevent liver damage in people on tuberculosis treatment